WO2025024561A1

WO2025024561A1 - Methods and systems for treating sleep disordered breathing

Info

Publication number: WO2025024561A1
Application number: PCT/US2024/039358
Authority: WO
Inventors: Shri Prabha SHIVRAM; Mitchell Patrick TURLEY; Phoebe Sarah DIJOUR; Anders William James Sideris
Original assignee: Somnair, Inc.
Priority date: 2023-07-24
Filing date: 2024-07-24
Publication date: 2025-01-30

Abstract

The present disclosure provides a delivery system for a method for maintaining upper airway patency. The method includes placing at least one electrode into electrical communication with a target site of a palatal muscle, a pharyngeal muscle, and/or a nerve that innervates the palatal muscle and/or the pharyngeal muscle for a patient. The method further includes activating the at least one electrode to deliver an electrical signal to the target site. The target site may be selected to target specific muscles or nerves involved in upper airway function. The electrical signal stimulates motor neurons or muscle fibers to cause contraction of the targeted muscles, thereby maintaining upper airway patency. The delivery system includes at least one electrode, a power source, and a controller in communication with the at least one electrode and programmed to direct delivery of an electrical signal, via the electrode, to the target site.

Description

Methods and Systems for Treating Sleep Disordered Breathing

CROSS-REFERENCE TO RELATED APPLICATION(S)

[0001] This application is a PCT international application that claims the benefit of priority of U.S. Provisional Application No. 63/515,165, filed July 24, 2023, entitled “Methods and Systems for Treating Sleep Disordered Breathing.”

[0002] The contents of each of the above referenced applications are hereby incorporated by reference in its entirety.

TECHNICAL FIELD

[0003] The present disclosure relates to methods and systems for treating sleep disordered breathing by activation of the palatal and pharyngeal musculature by neuromodulation.

BACKGROUND

[0004] Sleep disordered breathing (SDB) is a condition where breathing pauses or is disturbed during sleep. Obstructive sleep apnea (OSA) is a highly prevalent form of sleep disordered breathing characterized by repeated airway obstruction during sleep causing airflow limitation or cessation. Repeated airflow limitation or cessation leads to hypoxemia due to reduced ventilation of the lungs and hypercarbia or increased carbon dioxide levels in the blood. Hypercarbia leads to repeated arousals and an increase in activity of the airway muscles to open the airway and restore airflow. Hypoxemia leads to repeated arousals during sleep, limiting the patient’s ability to achieve restful sleep, and an increase in sympathetic activity leading to increased heart rate and blood pressure. Chronic and untreated hypoxemia as a result of airway obstruction increases the risk of hypertension, cerebrovascular events, cardiovascular events and metabolic disorders such as diabetes. Following arousal and restoration of airflow, the patient returns to sleep and further airway collapse occurs, leading to further airflow limitation, arousal and the aforementioned physiological effects. Repeated arousals lead to daytime sleepiness and poor cognitive function as a result of poor sleep quality. Snoring is the pathognomic sign of upper airway obstruction in sleep disordered breathing. Simple snoring represents a syndrome whereby airflow cessation (apnea) and airflow limitation (hypopnea) is less frequent and incurs less cerebro- and cardiovascular risk, however it is disruptive to the sleeping environment and bed partner. Simple snoring or snoring without OSA is generally defined as apnea-hypopnea index (AHI) less than 5 per hour. Mild OSA is generally defined as AHI<15, moderate as AHI 15-30 and severe as >30.

[0005] Multiple mechanisms contribute to obstruction and airflow limitation, these include anatomical and physiological factors. Anatomical factors include soft tissue and craniofacial anatomy, airway volume and tissue collapsibility. Physiological factors include neuromuscular control, loop-gain and arousal threshold. A key mechanism by which airflow limitation occurs is reduced neuromuscular control in the upper airway musculature that intermittently and repeatedly leads to airway collapse and obstruction. Left untreated, OSA affects daytime sleepiness and function and incurs cardiovascular, metabolic, and stroke risk.

[0006] Continuous positive airway pressure (CPAP) is the gold-standard first-line treatment for OSA of all phenotypes. It is highly efficacious for patients who adhere, but up to 50% of patients are non-adherent to CPAP treatment. Surgical options are available to patients who are intolerant to CPAP therapy to seek disease alleviation; however, not all phenotypes of OSA are well-treated by surgery. A particular phenotype is complete concentric collapse of the palate (CCCp), characterized by frequent complete retropalatal and lateral velopharyngeal wall collapse. It affects up to 30% of patients with OSA and is associated with greater disease severity (more frequent and severe airway collapse), and a higher propensity to CPAP failure. Modem upper airway surgery and neurostimulation techniques are only partially effective in treating CCCp. Contemporary neurostimulation approaches have focused on the hypoglossal nerve, which is contraindicated for patients with CCCp, and more recently the ansa cervicalis nerve.

[0007] Contemporary neurostimulation approaches for sleep disordered breathing target the largest airway dilator muscle, the genioglossus, causing protrusion of the tongue, an increase in airway volume and improved airflow. Ansa cervicalis stimulation has been proposed to address collapse of the lateral wall musculature by activation of the infrahyoid strap muscles leading to caudal tracheal traction and stiffening of the lateral walls of the pharynx. However, concentric collapse of the palate, a combination of lateral oropharyngeal/velopharyngeal wall collapse, and anteroposterior oropharyngeal/velopharyngeal airway collapse, occurs independent of these mechanisms and neurostimulation approaches that directly target this overlooked mechanism have not been proposed or explored by the field.

[0008] The present disclosure is directed to overcoming one or more of these above-referenced challenges.

SUMMARY OF THE DISCLOSURE

[0009] According to certain aspects of the disclosure, systems, methods, and computer readable memory are disclosed for treating sleep disordered breathing.

[0010] In some cases, a method for maintaining upper airway patency may include: placing, for a patient, at least one electrode into electrical communication with a target site of a palatal muscle, a pharyngeal muscle, and/or a nerve that innervates the palatal muscle and/or the pharyngeal muscle; and activating the at least one electrode to deliver an electrical signal to the target site.

[0011] In some cases, a delivery system placed internally in an oral cavity, nasal cavity, oropharynx, and/or nasopharynx may include: at least one electrode configured to deliver an electrical signal to a target site that is a nerve or muscle; a power source in wired or wireless communication with the at least one electrode; and a controller in communication with the at least one electrode and programmed to direct delivery of the electrical signal by the at least one electrode to the target site. [0012] Additional objects and advantages of the disclosed technology will be set forth in part in the description that follows, and in part will be apparent from the description, or may be learned by practice of the disclosed technology.

[0013] It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the disclosed technology, as claimed.

BRIEF DESCRIPTION OF THE DRAWINGS

[0014] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate various exemplary aspects and together with the description, serve to explain the principles of the disclosed technology.

[0015] FIG. 1 depicts a flowchart of a method for treating sleep disordered breathing by neuromodulation of nerves to the palatal and pharyngeal musculature.

[0016] FIG. 2 depicts a flowchart of a method for treating sleep disordered breathing by neuromodulation of the palatal and pharyngeal musculature.

[0017] FIG. 3 depicts a flowchart of a method for treating sleep disordered breathing by neuromodulation of nerves to the palatal and pharyngeal musculature and activation of the palatal and pharyngeal musculature.

[0018] FIG. 4 depicts a schematic representation of nerves to the palatal and pharyngeal musculature and the palatal and pharyngeal musculature.

[0019] FIG. 5 depicts a schematic representation of an intraoral view of the palatal and pharyngeal musculature.

[0020] FIG. 6 depicts a flowchart of neuromodulation of the intrinsic and extrinsic musculature of the tongue.

[0021] FIG. 7 depicts a schematic representation of the intrinsic and extrinsic tongue musculature.

[0022] FIG. 8 depicts a flowchart of neuromodulation of nerves to the palatal and pharyngeal musculature and neuromodulation of the hypoglossal nerve and ansa cervicalis nerve.

[0023] FIG. 9 depicts a flowchart of neuromodulation of the palatal and pharyngeal musculature and neuromodulation of the hypoglossal nerve and ansa cervicalis nerve.

[0024] FIG. 10 depicts a flow chart of neuromodulation of nerves to the palatal and pharyngeal musculature, neuromodulation of the palatal and pharyngeal musculature, and neuromodulation of the intrinsic and extrinsic tongue musculature.

[0025] FIG. 11 depicts a flowchart of neuromodulation of nerves to the palatal and pharyngeal musculature, neuromodulation of the palatal and pharyngeal musculature, and neuromodulation of the hypoglossal and ansa cervicalis nerve.

[0026] FIG. 12 depicts a flow chart of neuromodulation of nerves to the palatal and pharyngeal musculature, neuromodulation of the palatal and pharyngeal musculature, neuromodulation of the intrinsic and extrinsic tongue musculature, and neuromodulation of the hypoglossal and ansa cervicalis nerve. [0027] FIG. 13 depicts a schematic diagram of a non-implantable neuromodulation system.

[0028] FIG. 14 depicts a schematic diagram of an implantable neuromodulation system.

[0029] FIG. 15 depicts a schematic diagram of an embodiment of a neuromodulation therapy delivery system.

[0030] FIG. 16A depicts a schematic diagram of an embodiment of a neuromodulation therapy delivery system.

[0031] FIG. 16B depicts a schematic diagram of an embodiment of a neuromodulation therapy delivery system (side view).

[0032] FIG. 17 depicts a diagram of a charging case and remote subsystem of a neuromodulation therapy delivery system.

[0033] FIG. 18 depicts a schematic diagram of an embodiment of a neuromodulation therapy delivery system. Left: An embodiment demonstrating placement of an electrode at the superomedial insertion of the palatoglossus and an electrode placed on the retromolar trigone. Right: An embodiment demonstrating placement of an electrode at the superomedial insertion of the palatoglossus and an electrode placed on the third mandibular molar tooth. Far right: An embodiment demonstrating a non-conductive coating and a receiving electrode on the third mandibular molar tooth.

[0034] FIG. 19 depicts a schematic diagram of an embodiment of a neuromodulation therapy delivery system demonstrating placement of multiple electrodes placed proximate to various muscle targets in the palate and pharynx.

[0035] FIG. 20 depicts a schematic diagram of an embodiment of a neuromodulation therapy delivery system demonstrating placement of multiple electrode arrays placed proximate to various muscle targets in the palate and pharynx.

[0036] FIG. 21 depicts a schematic diagram of an embodiment of a neuromodulation therapy delivery system demonstrating placement of multiple electrodes placed proximate to the superior and inferior extremes of the palatopharyngeus and palatoglossus muscles (sagittal view).

[0037] FIG. 22 depicts a schematic diagram of an embodiment of a neuromodulation therapy delivery system demonstrating custom, patient specific electrode placement and system components.

[0038] FIG. 23 depicts a schematic diagram of an embodiment of a neuromodulation therapy delivery system demonstrating an electrode array, batteries designed to provide stimulation to tongue muscles in contact with the inferior aspect of the device.

[0039] FIG. 24 depicts an example system that may execute techniques presented herein.

DETAILED DESCRIPTION

[0040] The present disclosure relates to methods and systems for treating sleep disordered breathing in a patient suffering therefrom by activating the palatal and pharyngeal musculature by neuromodulation. 1. Introduction

[0041] In an aspect, a method for improving sleep disordered breathing in a patient suffering therefrom comprises delivering a neuromodulation signal (such as an electrical or magnetic or ultrasound or piezoelectric or radiation signal or electromagnetic signal or radiofrequency or mechanical or chemical or optical or sound signal or any other signal, and/or any combination therein) to a nerve that innervates a palatal muscle and/or a pharyngeal muscle; and activating the electrode or electrodes to deliver a neuromodulation signal (such as an electrical or magnetic or ultrasound or radiofrequency or mechanical or chemical or optical or sound signal, and/or any combination therein) to the target site of the nerve or muscle, in order to improve the patient’s sleep disordered breathing.

[0042] In another aspect, a method for improving sleep disordered breathing in a patient suffering therefrom comprises delivering a neuromodulation signal (such as an electrical or magnetic or ultrasound or piezoelectric or radiation signal or electromagnetic signal or radiofrequency or mechanical or chemical or optical or sound signal or any other signal, and/or any combination therein) to a target site where that target site is a palatal muscle and/or pharyngeal muscle, or nerve that innervates a palatal muscle and/or a pharyngeal muscle, including: a tensor veli palatini muscle, a levator veli palatini muscle, a palatopharyngeus muscle, a palatoglossus muscle, a musculus uvulae muscle, a superior constrictor muscle, a middle constrictor muscle, and/or any combination therein, in order to improve the patient’s sleep disordered breathing.

[0043] In another aspect, a method for improving sleep disordered breathing in a patient suffering therefrom comprises of delivering a neuromodulation signal (such as an electrical or magnetic or ultrasound or piezoelectric or radiation signal or electromagnetic signal or radiofrequency or mechanical or chemical or optical or sound signal or any other signal, and/or any combination therein) to a target site where that target site is an intrinsic tongue muscle such as a superior longitudinal muscle, or inferior longitudinal muscle, or transverse muscle or vertical muscle, or an extrinsic tongue muscle such as a genioglossus or hyoglossus or styloglossus, and/or any combination therein, in order to improve the patient’s sleep disordered breathing.

[0044] In another aspect, a method for improving sleep disordered breathing in a patient suffering therefrom comprises of delivering a neuromodulation signal (such as an electrical or magnetic or ultrasound or piezoelectric or radiation signal or electromagnetic signal or radiofrequency or mechanical or chemical or optical or sound signal or any other signal, and/or any combination therein) to a target site of a hypoglossal nerve, an ansa cervicalis nerve, a branch of the pharyngeal plexus to the palatopharyngeus muscle, a branch of the pharyngeal plexus to the middle constrictor muscle, a sternothyroid muscle, a thyrohyoid muscle, an omohyoid muscle, a sternohyoid muscle, and/or any combination therein, in order to improve the patient’s sleep disordered breathing.

[0045] In another aspect, a method for improving sleep disordered breathing in a patient suffering therefrom comprises of delivering a neuromodulation signal (such as an electrical or magnetic or ultrasound or piezoelectric or radiation signal or electromagnetic signal or radiofrequency or mechanical or chemical or optical or sound signal or any other signal, and/or any combination therein) to a target site of a hypoglossal nerve, an ansa cervicalis nerve, a branch of the pharyngeal plexus to the palatopharyngeus muscle, a branch of the pharyngeal plexus to the middle constrictor muscle, a branch of the pharyngeal plexus to a pharyngeal muscle, a branch of the pharyngeal plexus to an airway muscle, a cranial nerve, a vagus nerve, a glossopharyngeal nerve, a trigeminal nerve, a branch of the trigeminal nerve, a maxillary nerve, a branch of the maxillary nerve, a mandibular nerve, a branch of a mandibular nerve, a spinal nerve root innervating a pharyngeal muscle, a spinal nerve root innervating an airway muscle, a spinal nerve root innervating a diaphragm muscle, a brainstem location innervating a pharyngeal muscle, a brainstem location innervating an airway muscle, a brainstem location innervating a diaphragm muscle, a sternothyroid muscle, a thyrohyoid muscle, an omohyoid muscle, a sternohyoid muscle, and/or any combination therein, in order to improve the patient’s sleep disordered breathing.

[0046] In another aspect, a method for improving sleep disordered breathing in a patient suffering therefrom comprises delivering a neuromodulation signal (such as an electrical or magnetic or ultrasound or piezoelectric or radiation signal or electromagnetic signal or radiofrequency or mechanical or chemical or optical or sound signal or any other signal, and/or any combination therein) to a target site where that target site is a nerve that innervates a palatal muscle and/or a pharyngeal muscle; and activating the electrode or electrodes to deliver a neuromodulation signal (such as an electrical or magnetic or ultrasound or piezoelectric or radiation signal or electromagnetic signal or radiofrequency or mechanical or chemical or optical or sound signal or any other signal, and/or any combination therein) to the target site of the nerve or muscle, and/or a target site where that target site is a palatal muscle and/or pharyngeal muscle, or nerve that innervates a palatal muscle and/or a pharyngeal muscle, including: a tensor veli palatini muscle, a levator veli palatini muscle, a palatopharyngeus muscle, a palatoglossus muscle, a musculus uvulae muscle, a superior constrictor muscle, a middle constrictor muscle, and/or to a target site where that target site is an intrinsic tongue muscle such as a superior longitudinal muscle, or inferior longitudinal muscle, or transverse muscle or vertical muscle, or an extrinsic tongue muscle such as a genioglossus or hyoglossus or styloglossus, and/or a target site of a hypoglossal nerve, an ansa cervicalis nerve, a branch of the pharyngeal plexus to the palatopharyngeus muscle, a branch of the pharyngeal plexus to the middle constrictor muscle, a sternothyroid muscle, a thyrohyoid muscle, an omohyoid muscle, a sternohyoid muscle, and/or any combination therein, in order to improve the patient’s sleep disordered breathing.

[0047] In another aspect, a method for improving sleep disordered breathing in a patient suffering therefrom comprises delivering a neuromodulation signal (such as an electrical or magnetic or ultrasound or piezoelectric or radiation signal or electromagnetic signal or radiofrequency or mechanical or chemical or optical or sound signal or any other signal, and/or any combination therein) to a target site where that target site is a nerve that innervates a palatal muscle and/or a pharyngeal muscle; and activating the electrode or electrodes to deliver a neuromodulation signal (such as an electrical or magnetic or ultrasound or piezoelectric or radiation signal or electromagnetic signal or radiofrequency or mechanical or chemical or optical or sound signal or any other signal, and/or any combination therein) to the target site of the nerve or muscle, and/or a target site where that target site is a palatal muscle and/or pharyngeal muscle, or nerve that innervates a palatal muscle and/or a pharyngeal muscle, including: a tensor veli palatini muscle, a levator veli palatini muscle, a palatopharyngeus muscle, a palatoglossus muscle, a musculus uvulae muscle, a superior constrictor muscle, a middle constrictor muscle, and/or to a target site where that target site is an intrinsic tongue muscle such as a superior longitudinal muscle, or inferior longitudinal muscle, or transverse muscle or vertical muscle, or an extrinsic tongue muscle such as a genioglossus or hyoglossus or styloglossus, and/or a target site of a hypoglossal nerve, an ansa cervicalis nerve, a branch of the pharyngeal plexus to the palatopharyngeus muscle, a branch of the pharyngeal plexus to the middle constrictor muscle, a branch of the pharyngeal plexus to a pharyngeal muscle, a branch of the pharyngeal plexus to an airway muscle, a cranial nerve, a vagus nerve, a glossopharyngeal nerve, a trigeminal nerve, a branch of the trigeminal nerve, a maxillary nerve, a branch of the maxillary nerve, a mandibular nerve, a branch of a mandibular nerve, a cranial root of the accessory nerve, a spinal nerve root innervating a pharyngeal muscle, a spinal nerve root innervating an airway muscle, a spinal nerve root innervating a diaphragm muscle, a brainstem location innervating a pharyngeal muscle, a brainstem location innervating an airway muscle, a brainstem location innervating a diaphragm muscle, a sternothyroid muscle, a thyrohyoid muscle, an omohyoid muscle, a sternothyroid muscle, a thyrohyoid muscle, an omohyoid muscle, a sternohyoid muscle, and/or any combination therein, in order to improve the patient’s sleep disordered breathing.

[0048] In another aspect, a therapy delivery system placed internally in the oral and/ or nasal cavity and/or oropharynx and/or nasopharynx comprising of: at least one electrode configured to deliver a neuromodulation signal (such as an electrical or magnetic or ultrasound or piezoelectric or radiation signal or electromagnetic signal or radiofrequency or mechanical or chemical or optical or sound signal or any other signal, and/or any combination therein) to a target site that is a nerve or muscle; a power source in wired or wireless communication with the electrode; and a controller in communication with the electrode and programmed to direct delivery of an electrical or other signal by the electrode to the target site, in order to improve the patient’s sleep disordered breathing.

[0049] Delivery of neuromodulation signals can improve a patient’s sleep disordered breathing.

[0050] Neuromodulation may also be applied to other disease states such as central sleep apnea, sleep disorders, xerostomia, dysphagia, hypertension, hypotension, autonomic dysfunction, heart rate regulation, blood pressure regulation, migraine, headache, acute pain, chronic pain, neuropathic pain, muscular pain, superficial pain, dermatomal pain, back pain, menstrual pain, dysthesia, epilepsy, seizures, movement disorders, Parkinson’s disease, tremors, paresis, palsy, synkinesis, spasticity, dystonia, autoimmune disorders of the central nervous system, autoimmune disorders of the peripheral nervous system, autoimmune disorders of the autonomic nervous system, inflammatory disorders of the central nervous system, inflammatory disorders of the peripheral nervous system, inflammatory disorders of the autonomic nervous system, visual disorders, auditory disorders, psychiatric disorders, mood disorders, insomnias, parasomnias, primary peripheral nervous system disorders, secondary peripheral nervous system disorders, primary central nervous system disorders, secondary central nervous system disorders, muscular dysfunction, neuromuscular dysfunction, urinary dysfunction, bowel dysfunction, anorectal dysfunction, constipation, hearing loss, tinnitus, cranial nerve disorders, vestibular dysfunction, hormonal regulation, trauma including peripheral and central nervous system, cognitive dysfunction, dementia, neuropsychiatric disorders, exocrine dysfunction, endocrine dysfunction, neurotransmitter modulation, cardiac pacemaking, arrythmias, dysrhythmias, tacharrythmias, bradyarrythmias, tachycardia, bradycardia, nasal disorders, sinus disorders, sinonasal disorders, inflammatory nasal disorders, inflammatory sinus disorders, inflammatory sinonasal disorders, rhinitis, rhinosinusitis, allergic rhinitis, non-allergic rhinitis, chronic rhinitis, acute rhinitis, acute sinusitis, recurrent acute sinusitis, chronic sinusitis, acute rhinosinusitis, recurrent acute rhinosinusitis, chronic rhinosinusitis, olfactory disorders, hearing loss, hearing disorders, Eustachian tube disorders, middle ear disorders, external ear disorders, inner ear disorders, vestibulocochlear disorders, balance disorders, swallowing disorders, taste disorders, salivary secretion disorders, voice disorders, speaking disorders, tumours, malignancy, benign disease, carcinoma, sarcoma and/or any other condition that may be affected by neuromodulation and/or any combination therein. The foregoing are just a few examples of conditions in which neuromodulation may be of benefit, however embodiments of the invention described hereafter are not necessarily limited to treating only the above-described conditions.

[0051] Thus, methods and systems of the present disclosure may be improvements to treating sleep disordered breathing and/or neuromodulation.

2, Neuromodulation Embodiments

[0052] Neuromodulation has potential to treat many physiological conditions and disorders and diseases. Neuromodulation refers to alteration of the activity, electrical and chemical of the nervous system, including the central, peripheral and autonomic nervous system. Such alteration of the electrical and chemical activity of the nervous system can include activation, inhibition, stimulation, modification, regulation of the nervous system and/or any combination therein. By altering this activity, several effects may be achieved. For example, motor nerves may be stimulated to induce muscle contraction. Sensory nerves may be activated to provide sensory feedback to an organ and/or patient, and/or inhibited to relieve pain or other sensory functions. Autonomic nerves may be modulated to regulate physiological activity of involuntary autonomic functions such as heart rate, blood pressure, respiration, digestive function, thermoregulation, reflex regulation, bladder and bowel function, sexual function, exocrine function, endocrine function, paracrine function, neuromuscular function, neuromuscular junction function, neurotransmitter release, neurotransmitter inhibition, neurotransmitter regulation, mucosal function, skin function or integumentary function, inflammation, allergic inflammation, non-allergic inflammation, acute inflammation, chronic inflammation, cellular function, cellular communication and/or any combination therein. The nervous system may also be modulated to regulate exocrine and endocrine and paracrine functions such as hormone secretion, enzyme secretion, protein secretion, regulation of metabolism, control of growth and development, maintenance of fluid and electrolyte balance, regulation of reproductive processes, modulation of stress responses, glycemic control, sweat production and secretion, lubrication, salivary production and secretion, mucus production and secretion, waste excretion, mucosal function, vasoconstriction, vasodilation, neurotransmitter regulation, neurotransmitter release, neurotransmitter inhibition, chemical regulation, chemical release, chemical inhibition, hormone release, hormone regulation, hormone inhibition, inflammation, allergic inflammation, non-allergic inflammation, acute inflammation, chronic inflammation, cellular function, cellular communication, lacrimation and lactation. While embodiments of the present disclosure may be disclosed for use in patients with specific conditions, the embodiments may be used in conjunction with any patient/portion of a body where nerve modulation may be desired.

[0053] The present disclosure relates to methods and systems for treating sleep disordered breathing in a patient suffering therefrom by activating the palatal and pharyngeal musculature by neuromodulation. The present disclosure also relates to methods and systems for treating sleep disordered breathing in a patient suffering therefrom by activating palatal and pharyngeal and tongue and strap musculature by neuromodulation, and/or any combination therein. Sleep disordered breathing includes snoring, sleep apnea, upper airway resistance syndrome, hypoventilation syndrome, obesity hypoventilation syndrome. Sleep apnea includes obstructive sleep apnea, central sleep apnea and mixed sleep apnea.

[0054] Reference to “improving” a patient's SDB includes treating, reducing the symptoms of, mitigating, or preventing the SDB. In certain aspects, a method of improving a patient's SDB is preventative as opposed to reactionary in nature. In other words, a method of improving a patient's SDB according to certain aspects involves preventing SDB as opposed to detecting an apnea or hypopnea event, for example, and responding to such detected event. By preventing SDB, treatment method can reduce the potential for airway collapse as opposed to reacting to a documented event. In other aspects improving a patient’s SDB may consist of reacting to a respiratory event such as an apnea or hypopnea. As used herein, “modulation”, “neural modulation”, “neuromodulation,” “neuromodulate,” “neurostimulation,” “neuro-stimulate," "stimulation," or "stimulate” refers to exciting or inhibiting or activating or stimulating or modifying or regulating neural activity. A patient suffering from SDB includes a mammal, such as a human being.

[0055] Multiple mechanisms contribute to obstruction and airflow limitation in sleep disordered breathing, these include anatomical and physiological factors. Anatomical factors include soft tissue and craniofacial anatomy, airway volume and tissue collapsibility. Physiological factors include neuromuscular control, loop-gain and arousal threshold. A key mechanism by which airflow limitation occurs is reduced neuromuscular control in the upper airway musculature that intermittently and repeatedly leads to airway collapse and obstruction. Left untreated, OSA affects daytime sleepiness and function and incurs cardiovascular, metabolic, and stroke risk.

[0056] Continuous positive airway pressure (CPAP) is the gold-standard first-line treatment for OSA of all phenotypes. It is highly efficacious for patients who adhere, but up to 50% of patients are non-adherent to CPAP treatment. Surgical options are available to patients who are intolerant to CPAP therapy to seek disease alleviation; however, not all phenotypes of OSA are well-treated by surgery. A particular phenotype is complete concentric collapse of the palate (CCCp), characterized by frequent complete retropalatal and lateral velopharyngeal wall collapse. It affects up to 30% of patients with OSA and is associated with greater disease severity (more frequent and severe airway collapse), and a higher propensity to CPAP failure. Modem upper airway surgery and neurostimulation techniques are only partially effective in treating CCCp. Contemporary neurostimulation approaches have focused on the hypoglossal nerve, which is contraindicated for patients with CCCp, and more recently the ansa cervicalis nerve. Other anatomical phenotypes, sites and patterns of airway collapse include anteroposterior, lateral and concentric collapse at the nasopharynx, velum or soft palate, uvula, oropharynx including the lateral walls of the pharynx, tonsils, posterior wall of the pharynx, tongue, tongue base, hypopharynx, hyoid bone, larynx, epiglottis, supraglottis, glottis and subglottis.

[0057] Contemporary neurostimulation approaches for sleep disordered breathing target the largest airway dilator muscle, the genioglossus, causing protrusion of the tongue, an increase in airway volume or prevention of posterior collapse and improved airflow. Ansa cervicalis stimulation has been proposed to address collapse of the lateral wall musculature by activation of the infrahyoid strap muscles, caudal tracheal traction and stiffening of the lateral walls of the pharynx, preventing or reversing lateral wall collapse, increasing airway volume and improving airflow. However, concentric collapse of the airway, a combination of lateral oropharyngeal/lateral velopharyngeal wall collapse, and anteroposterior oropharyngeal/velopharyngeal collapse, occurs independent of these mechanisms and neurostimulation approaches that directly target this overlooked mechanism have not been proposed or explored by the field. Further, current thought paradigms amongst experts in the field center on activation of the airway musculature to increase airway diameter during periods of obstruction, reversing the collapsed state of the airway. Within this paradigm exists the assumption that initiation of neuromuscular activation through provision of external neuromodulation to airway dilators during the inspiratory phase is the primary mechanism by which airway collapse can be treated. However, pre-inspiratory and expiratory activation of airway dilators and other airway muscles may also prevent airway collapse to the extent that pharyngeal airflow and lung ventilation is maintained through periods of negative pressure and pharyngeal collapsibility. Further, the role of airway muscles not considered by experts in the field to be classic airway dilators in preventing airway collapse by tetanic or sub-tetanic or partial or full control of their collapsibility has not been explored by experts.

[0058] In an embodiment, a method and system for treating sleep disordered breathing may be provided to patients after polysomnographic diagnosis of sleep disordered breathing, an anatomical assessment such as a radiological examination and/or an endoscopic examination and/or a drug induced endoscopic examination and/or an awake endoscopic examination and/or a laboratory examination and/or physiologic examination and/or any technological examination, screening methods for sleep disordered breathing, clinical suspicion of sleep disordered breathing including a history of symptoms and signs of sleep disordered breathing and/or physical examination findings suggestive of sleep disordered breathing including oral examination, endoscopic examination of the oral cavity/ and or nasal cavity and/or nasopharynx and/or oropharynx and/or hypopharynx and/or tongue and/or tongue base and or supraglottis and/or glottis and/or subglottis, a neck examination, a craniofacial examination, a facial bone examination, an airway examination, a dental examination, and/or or any other method used to screen for and/or diagnose sleep disordered breathing and/or any combination therein. In an embodiment, a method and system for sleep disordered breathing may be provided to a patient by a health practitioner such as a physician and/or surgeon and/or dentist and/or oral health practitioner and/or oral hygienist and/or dental assistant and/or nurse and/or any healthcare provider.

[0059] In an embodiment, a method and system for treating sleep disordered breathing may be provided as and/or in combination with and/or incorporated into a retainer, and/or a non-retainer form, and/or a stent form, and/or a non-implant form, and/or an implant form, and/or a positive airway pressure therapy and/or a continuous positive airway pressure therapy and/or a mandibular advancement device and/or a mandibular advancement therapy and/or a mandibular advancement procedure and/or a mandibular advancement surgery, and/or a surgery for sleep disordered breathing including a nasal surgery and/or a nasopharyngeal surgery, and/or an oral cavity surgery and/or an oropharyngeal surgery and/or a palate surgery and/or a tonsil surgery and/or a lateral pharyngeal wall surgery and/or a pharyngeal surgery and/or an oropharyngeal surgery and/or a hypopharyngeal surgery and/or a tongue surgery and/or a tongue base surgery and/or a supraglottic surgery and/or an epiglottic surgery and/or a glottic surgery, and/or a subglottic surgery and/or a craniofacial surgery and/or a facial bone surgery and/or a hyoid bone surgery and/or a dental surgery and/or a neck surgery and/or a minimally-invasive procedure and/or non-invasive procedure, a positional therapy and/or device and/or drug, an orthodontic therapy and/or device and/or drug and/or procedure and/or surgery, a dental therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery, an endodontic therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery, a sleep therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery, a sleep disorder therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery, a mouth guard device and/or appliance and/or retainer and/or prothesis, a bruxism therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery, a nasal therapy and/or device and or prosthesis and/or drug, and/or a nasopharyngeal therapy and/or device and/or prosthesis and/or drug, a nasal airway therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery, and/or an oral cavity therapy and/or device and/or prosthesis and/or retainer and/or drug, an oropharyngeal therapy and/or device and/or prosthesis and/or drug, and/or a palate therapy and/or device and/or prosthesis and/or drug, a tonsil therapy and/or device and/or prosthesis and/or drug, a lateral pharyngeal wall therapy and/or device and/or prosthesis and/or drug, a hypopharyngeal therapy and/or device and or prosthesis and/or drug, a tongue therapy and/or device and/or prosthesis and/or drug, a tongue base therapy and/or device and/or prosthesis and/or drug, a supraglottic therapy and/or device and/or prosthesis and/or drug, an epiglottic therapy and/or device and/or prosthesis and/or drug, and/or a glottic therapy and/or device and/or prosthesis and/or drug, a subglottic therapy and/or device and/or prosthesis and/or drug, a craniofacial therapy and/or device and/or prosthesis and/or drug, a facial bone therapy and/or device and or prosthesis and/or drug, and/or a dental therapy and/or device and/or retainer and/or prosthesis and/or drug, a neck therapy and/or device and/or retainer and/or prosthesis and/or drug, and/or a non-invasive therapy and/or device and/or prosthesis and/or drug, a neuromodulation therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system, a trigeminal nerve therapy and/or device and/or drug and/or procedure and/or surgery and/or method and/or system, a hypoglossal nerve stimulation therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system, an ansa cervicalis nerve stimulation therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system, a glossopharyngeal nerve stimulation therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system, a vagus nerve stimulation therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system, a facial nerve therapy and/or device and/or drug and/or procedure and/or surgery and/or method and/or system, an accessory nerve stimulation therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system, a cranial nerve stimulation therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system, a peripheral nerve and/or nervous system nerve stimulation therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system, a central nervous system therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system, an autonomic nervous system therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system, a trigeminal nerve stimulation therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system, and/or any therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system that is intended to treat sleep disordered breathing, and/or any combination therein. The foregoing are just a few examples of a therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system for treatment of sleep disordered breathing, however embodiments of the invention described hereafter are not necessarily limited to the above-described therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system, and/or any combination therein.

[0060] In an embodiment, following provision of a method and system for treating sleep disordered breathing, the effect of a method and system may be assessed by an aforementioned polysomnographic examination, an aforementioned radiological examination, an aforementioned endoscopic examination, an aforementioned drug induced endoscopic examination, an aforementioned awake endoscopic examination, an aforementioned clinical history and/or examination, an aforementioned laboratory examination, an aforementioned technological examination, and/or any aforementioned examination, and/or any combination therein. Following assessment of an aforementioned examination of an effect of a method and system of treating sleep disordered breathing, a neuromodulation parameter may be titrated based on information gained from an aforementioned examination, and/or information produced by and/or detected by and/or sensed by and/or stored by and/or provided by a system for treating sleep disordered breathing. [0061] In an embodiment, improving a patient’s sleep disordered breathing may represent an increase in an airway volume, reduction in airway obstruction, increase in airway patency, reduction in a critical closing pressure of the pharynx and/or palate, increase in a pharyngeal and/or palatal opening pressure, decrease in airway tissue collapsibility, decrease in airway muscle collapsibility, increase in a pharyngeal airflow, increase in lung ventilation, decrease in frequency of apnea, decrease in frequency of hypopnea, decrease in apnea-hypopnea index, increase in oxygen desaturation index, increase in lowest oxygen saturation, decrease in hypoxic time, decrease in relative hypoxic time, decrease in hypercarbia, improvement in sleep quality, improvement in sleep efficiency, improvement in sleep quality, improvement in daytime sleepiness, improvement in snoring, decrease in arousal frequency, increase in total sleep time, decrease in wakefulness after sleep onset, improvement in a stage of sleep, improvement in REM sleep, improvement in non-REM sleep, improvement in REM latency, decrease in central apnea frequency, improvement in mixed apnea frequency, improvement in number of respiratory events, improvement in supine respiratory events, improvement in lateral respiratory events, improvement in prone respiratory events, improvement in any sleep quality metric, improvement in any sleep disturbance, improvement in any sleep disorder, reduction in cardiovascular risk, reduction in cerebrovascular risk, reduction in metabolic risk, improvement in sleep onset latency, reduction in respiratory effort related arousal, improvement in circadian function, improvement in any polysomnographic parameter, improvement in any non-polysomnographic parameter, improvement in any sleep quality metric, improvement in nasal function, improvement in sinus function, improvement in sinonasal function, and/or any health benefit, and/or any combination therein.

[0062] The present disclosure relates to methods and systems for treating sleep disordered breathing in a patient suffering therefrom by activating the palatal and pharyngeal musculature by neuromodulation. The palate and pharyngeal musculature are innervated by branches of the trigeminal nerve (mandibular [V2] and maxillary [V3] divisions) and the pharyngeal plexus (a network of cranial nerve fibers from the cranial root of the accessory nerve, the vagus nerve and the glossopharyngeal nerve). The maxillary division of the trigeminal nerve has multiple branches including the lesser palatine nerve (LPN) which innervates the muscles of the palatal sling including the levator veli palatini (LVP), musculus uvulae (MU), the palatopharyngeus (PP), and the palatoglossus (PG) muscles. These muscles elevate the soft palate (LVP), retract the uvula anteriorly (MU) and caudally tension the lateral walls of the pharynx (PP, PG) respectively.

[0063] The mandibular branch of the trigeminal nerve has multiple branches including the nerve to tensor veli palatini (TVP) which innervates the tensor veli palatini muscle. This muscle tensions the soft palate in a lateral manner.

[0064] The pharyngeal plexus (a network of cranial nerve fibers from the cranial root of the accessory nerve, the vagus nerve and the glossopharyngeal nerve) has multiple branches to the palatal and pharyngeal musculature including the branch to levator veli palatini, the branch to palatopharyngeus, the branch to palatoglossus, the branch to superior constrictor (SC) and the branch to middle constrictor (MC) muscle. These muscles elevate the soft palate (LVP), caudally tension the lateral walls of the pharynx (PP, PG), and increase circumferential tone (SC, MC) in the pharynx respectively.

[0065] The tongue consists of both intrinsic and extrinsic muscles. Intrinsic muscles include the superior longitudinal, inferior longitudinal, transverse and vertical muscles. The superior and inferior longitudinal muscles shorten and widen the tongue, the transverse muscles elongate and narrow the tongue and the vertical muscles flatten the tongue. Extrinsic muscles include the genioglossus, styloglossus, hyoglossus and palatoglossus muscles. The genioglossus protrudes the tongue, the styloglossus and hyoglossus retrude the tongue, and elevate and depress its lateral margins respectively, the palatoglossus pulls the palate towards the posterior tongue.

[0066] Without wishing to be bound by a particular mechanism of action, stimulation of the nerves innervating this musculature, and the musculature itself, may prevent anteroposterior palate collapse in concert with caudal tensioning of the lateral walls, and increase circumferential tone in the pharynx, to circumferentially dilate and prevent collapse of the velopharynx and oropharynx. Further, stimulation may assist in preventing posterior collapse of the tongue into the pharynx, either through active protrusion of the tongue or by increasing neuromuscular tone in order to prohibit tongue collapse during inspiration. As such, neuromodulation of nerves innervating these muscles and/or the muscles themselves may be a novel treatment for patients with OSA, in particular those with CCCp and multilevel airway obstruction. This stimulation may be delivered by electrical, ultrasound, magnetic, radiofrequency, mechanical, chemical, optical or sound energy, and/or any combination therein. This stimulation may be unilateral or bilateral stimulation. The foregoing are just a few examples of effects of neuromodulation on sleep disordered breathing, however embodiments of the invention described hereafter are not necessarily limited to the above-described effects.

[0067] Without wishing to be bound by a particular embodiment, the therapy delivery system may be placed internally in the oral cavity and/or nasal cavity and/or oropharynx and/or nasopharynx comprising of at least one electrode configured to deliver an electrical or other signal to a target site that is the aforementioned nerves or muscles; a power source in wired or wireless communication with the electrode; and a controller in communication with the electrode and programmed to direct delivery of an electrical or other signal by the electrode to the target site. The foregoing are just a few examples of a therapy delivery sleep system for sleep disordered breathing, however embodiments of the invention described hereafter are not necessarily limited to the above-described.

[0068] Without wishing to be bound by a particular embodiment, a method and system for treating sleep disordered breathing may be a closed-loop system, an open loop system and/or any combination therein. In an embodiment a method and system for treating sleep disordered breathing may be configured to achieve its therapeutic outcome using polysomnographic data and/or data from an anatomical assessment such as a radiological examination and/or an endoscopic examination and/or a drug induced endoscopic examination and/or an awake endoscopic examination and/or a laboratory examination and/or physiologic examination and/or any technological examination, clinical suspicion of sleep disordered breathing including a history of symptoms and signs of sleep disordered breathing and/or physical examination findings suggestive of sleep disordered breathing including oral examination, endoscopic examination of the oral cavity/ and or nasal cavity and/or nasopharynx and/or oropharynx and/or hypopharynx and/or tongue and/or tongue base, and or supraglottis and/or glottis and/or subglottis, a neck exam, a craniofacial examination, a facial bone examination, an airway exam, a dental exam, and/or or any other method used to screen for and/or diagnose sleep disordered breathing, and/or any data related to sleep physiology and/or a sleep disorder and/or sleep disorder pathophysiology, and/or any aforementioned examination and/or any combination therein. In an embodiment, a closed-loop system consists of sensing and/or measuring and/or monitoring of physiologic parameters and or/surrogates for sleep and/or sleep apnea and/or breathing, either processing data from those parameters and/or surrogates or directly controlling neurostimulation and communicating a signal to electrodes for stimulation of target anatomy. In another embodiment, an open-loop system consists of configuration of neurostimulation parameters based upon polysomnographic data and/or data from a home sleep study and/or data from another form of sleep study and/or data from an anatomical assessment such as a radiological examination and/or an endoscopic examination and/or a drug induced endoscopic examination and/or an awake endoscopic examination and/or a laboratory examination and/or physiologic examination and/or any technological examination and/or any aforementioned examination, and/or any combination therein. In this embodiment, neurostimulation parameters may be titrated and/or modulated and/or optimized by a patient and/or physician and/or surgeon and/or dentist and/or nurse and/or health practitioner and/or any combination therein to deliver custom neurostimulation therapy for each patient.

[0069] In an embodiment a method and system for treating sleep disordered breathing may be activated by a patient and/or physician and/or surgeon and/or dentist and/or nurse and/or health practitioner and/or any combination therein. In an embodiment a method and system for treating sleep disordered breathing may be activated by an algorithm consisting of input from position data, timing inputs, sleep architecture data, anatomical data, and physiological sleep parameters and/or any combination therein.

[0070] Without wishing to be bound by a particular embodiment at least one electrode may be placed internally in the head and/or neck, at or beneath or within a mucosal layer, at or beneath or within skin and/or a skin layer, at or beneath or within a muscle, at or in contact with a nerve or nerve fibers, at or within a blood vessel, at or within or in contact with soft tissue including a tendon and/or ligament and/or fascia and/or lymph node and/or adipose tissue, and/or any combination therein, proximate to a target that is the aforementioned nerves or muscles; a power source in wired or wireless communication with the electrode; and a controller in communication with the electrode and programmed to direct delivery of an electrical and/or other signal by the electrode to the target site. The foregoing are just a few examples of a therapy delivery sleep system for sleep disordered breathing, however embodiments of the invention described hereafter are not necessarily limited to the above-described.

[0071] In an embodiment at least one electrode may be deployed to a target site via permucosal/ transmucosal and/or percutaneous delivery, and/or any combination therein. In an embodiment, the electrode may be deployed to a target site via a needle delivery system and/or catheter delivery system and/or introducer delivery system and/or sheath delivery system and/or dilator deliver system and/or guidewire delivery system and/or balloon catheter delivery system, and/or stent delivery system and/or microcatheter delivery system and/or an image guided delivery system, and/or an endoscopic delivery system and/or an optical delivery system and/or any system that facilitates delivery and/or any combination therein.

[0072] Without wishing to be bound by a particular embodiment, a method and system for treating sleep disordered breathing may be delivered in a retainer, and/or a non-retainer form, and/or a stent form, and/or a non-implant form, and/or an implant form, and/or a continuous positive airway pressure therapy and/or a mandibular advancement device and/or a mandibular advancement therapy and/or a mandibular advancement procedure and/or a mandibular advancement surgery, and/or a surgery for sleep disordered breathing including a nasal surgery and/or a nasopharyngeal surgery, and/or an oral cavity surgery and/or an oropharyngeal surgery and/or a palate surgery and/or a tonsil surgery and/or a lateral pharyngeal wall surgery, and/or a hypopharyngeal surgery and/or a tongue surgery, and/or a tongue base surgery and/or a supraglottic surgery and/or an epiglottic surgery and/or a glottic surgery, and/or a subglottic surgery and/or a craniofacial surgery and/or a facial bone surgery and/or a hyoid bone surgery and/or a dental surgery and/or a neck surgery and/or a non-invasive procedure, a positional therapy and/or device and/or drug, an orthodontic therapy and/or device and/or drug and/or procedure and/or surgery, a dental therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery, an endodontic therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery, a sleep therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery, a sleep disorder therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery, a mouth guard device and/or appliance and/or retainer and/or prothesis, a bruxism therapy and/or device and/or retainer an/or prosthesis and/or drug and/or procedure and/or surgery, a nasal therapy and/or device and or prosthesis and/or drug, and/or a nasopharyngeal therapy and/or device and/or prosthesis and/or drug, a nasal airway therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery, and/or an oral cavity therapy and/or device and/or prosthesis and/or retainer and/or drug, an oropharyngeal therapy and/or device and/or prosthesis and/or drug, and/or a palate therapy and/or device and/or prosthesis and/or drug, a tonsil therapy and/or device and/or prosthesis and/or drug, a lateral pharyngeal wall therapy and/or device and/or prosthesis and/or drug, a hypopharyngeal therapy and/or device and or prosthesis and/or drug, a tongue therapy and/or device and/or prosthesis and/or drug, a tongue base therapy and/or device and/or prosthesis and/or drug, a supraglottic therapy and/or device and/or prosthesis and/or drug, an epiglottic therapy and/or device and/or prosthesis and/or drug, and/or a glottic therapy and/or device and/or prosthesis and/or drug, a subglottic therapy and/or device and/or prosthesis and/or drug, a craniofacial therapy and/or device and/or prosthesis and/or drug, a facial bone therapy and/or device and or prosthesis and/or drug, and/or a dental therapy and/or device and/or retainer and/or prosthesis and/or drug, a neck therapy and/or device and/or retainer and/or prosthesis and/or drug, and/or a non-invasive therapy and/or device and/or prosthesis and/or drug, a neuromodulation therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system, a trigeminal nerve therapy and/or device and/or drug and/or procedure and/or surgery and/or method and/or system, a hypoglossal nerve stimulation therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system, an ansa cervicalis nerve stimulation therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system, a glossopharyngeal nerve stimulation therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system, a vagus nerve stimulation therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system, a facial nerve therapy and/or device and/or drug and/or procedure and/or surgery and/or method and/or system, an accessory nerve stimulation therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system, a cranial nerve stimulation therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system, a peripheral nerve and/or nervous system nerve stimulation therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system, a central nervous system therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system, an autonomic nervous system therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system, a trigeminal nerve stimulation therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system, and/or any therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system that is intended to treat sleep disordered breathing, and/or any combination therein. The foregoing are just a few examples of a therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system for treatment of sleep disordered breathing, however embodiments of the invention described hereafter are not necessarily limited to the abovedescribed therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system, and/or any combination therein.

[0073] Without wishing to be bound by a particular embodiment, a method and system for treating sleep disordered breathing may modulate a nerve at its proximal origin and/or its foramen and/or it branch and/or its division and/or its distal component and/or its distal ending and/or its fibers and/or its motor endplate and/or its spinal root and/or its brainstem root and/or its central nervous system origin and/or its neuromuscular junction and/or the muscle it innervates and/or its sensory fibers and/or its motor fibers and/or its autonomic fibers and/or its ganglion and/or its axons and/or any peripheral and/or central and/or autonomic nervous system component, and/or any combination therein. Without wishing to be bound by a particular embodiment a method and system for treating sleep disordered breathing may modulate any physiological and/or chemical and/or electrical and/or neurochemical and/or biological component of its target site, and/or any combination therein.

[0074] Without wishing to be bound by a particular embodiment, in an embodiment where there is an implantable receiver in communication with one or more implanted electrodes comprising the neurostimulator subsystem, an oral appliance subsystem can include a programmable pulse generator unit for transmitting power, for example inductive power transmission, radiofrequency power transmission, or ultrasound power transmission among others, from the oral appliance subsystem to the implanted neurostimulator. In this embodiment, the implantable neurostimulator may be delivered through a percutaneous delivery system consisting of deployment to a target site via a needle delivery system and/or catheter delivery system and/or introducer delivery system and/or sheath delivery system and/or dilator deliver system and/or guidewire delivery system and/or balloon catheter delivery system, and/or stent delivery system and/or microcatheter delivery system and/or an image guided delivery system, and/or an endoscopic delivery system and/or an optical delivery system and/or any system facilitating placement and/or surgical placement and/or any combination therein. In this embodiment, a rechargeable battery in the oral appliance subsystem may be powered prior to use through wired or inductive energy transfer from a charging case and remote subsystem. In this embodiment, the case and remote subsystem also may function as a programming device that may be used to initiate terminate, and modulate therapy delivered by the oral appliance and neurostimulator subsystems via a bidirectional wired or wireless telemetry link. [0075] With reference to FIG. 1, in an aspect, a method 1 of treating sleep disordered breathing in a patient suffering therefrom comprises delivering a neuromodulation signal to a target site proximate to a lesser palatine nerve and/or nerve to tensor veli palatini and/or pharyngeal plexus branches to levator veli palatini, palatopharyngeus, palatoglossus, middle constrictor, and/or superior constrictor and/or any combination therein that innervates the palatal and/or pharyngeal musculature. A target site can be proximate to a lesser palatine nerve, and/or nerve to tensor veli palatini, and/or a pharyngeal plexus branch to a levator veli palatini, palatopharyngeus, palatoglossus, middle constrictor and/or superior constrictor, and/or any combination therein such that delivering a neuromodulation signal activates the motor fibres of these nerves and/or muscles. Method 1 further includes activating a levator veli palatini muscle, and/or musculus uvulae muscle, and/or palatopharyngeus muscle, and/or palatoglossus muscle, and/or tensor veli palatini muscle, and/or middle constrictor muscle, and/or superior constrictor muscle, and/or any combination therein. Method 1 further comprises improving the patient’s sleep disordered breathing via delivery of the neuromodulation signal. The foregoing are just a few examples of a method of neuromodulation, however embodiments of the invention described hereafter are not necessarily limited to the above-described methods.

[0076] With reference to FIG. 2, in an aspect, a method 2 of treating sleep disordered breathing in a patient suffering therefrom comprises delivering a neuromodulation signal to a target site proximate to a levator veli palatini muscle and/or musculus uvulae muscle and/or palatopharyngeus muscle and/or palatoglossus muscle and/or tensor veli palatini muscle and/or middle constrictor muscle and/or superior constrictor muscle and/or any combination therein. A target site can be proximate to a levator veli palatini muscle and/or musculus uvulae muscle and/or palatopharyngeus muscle and/or palatoglossus muscle and/or tensor veli palatini muscle and/or middle constrictor muscle and/or superior constrictor muscle and/or any combination therein such that delivering a neuromodulation signal activates the muscle fibers of these muscles thereby increasing their tone. Method 2 further comprises improving the patient’s sleep disordered breathing via delivery of the neuromodulation signal. The foregoing are just a few examples of a method of neuromodulation, however embodiments of the invention described hereafter are not necessarily limited to the above -de scribed methods. [0077] With reference to FIG. 3, in an aspect, a method 3 of treating sleep disordered breathing in a patient suffering therefrom comprises delivering a neuromodulation signal to a target site proximate to a lesser palatine nerve and/or nerve to tensor veli palatini and/or a pharyngeal plexus branch to a levator veli palatini, palatopharyngeus, palatoglossus, middle constrictor and/or superior constrictor and/or any combination therein that innervates the palatal and/or pharyngeal musculature, and/or any combination therein, and/or a target site proximate to a levator veli palatini muscle and/or musculus uvulae muscle and/or palatopharyngeus muscle and/or palatoglossus muscle and/or tensor veli palatini muscle and/or middle constrictor muscle and/or superior constrictor muscle and/or any combination therein. A target site can be proximate to a lesser palatine nerve and/or nerve to tensor veli palatini and/or pharyngeal plexus branches to levator veli palatini, palatopharyngeus, palatoglossus, middle constrictor and/or superior constrictor and/or any combination therein, and/or a levator veli palatini muscle and/or musculus uvulae muscle and/or palatopharyngeus muscle and/or palatoglossus muscle and/or tensor veli palatini muscle and/or middle constrictor muscle and/or superior constrictor muscle and/or any combination therein such that delivering a neuromodulation signal activates the motor fibres of these nerves and activates the muscle fibres of these muscles thereby increasing their tone. Method 3 further comprises improving the patient’s sleep disordered breathing via delivery of the nvent dulation signal. The foregoing are just a few examples of a method of neuromodulation, however embodiments of the invention described hereafter are not necessarily limited to the above-described methods.

[0078] With reference to FIG. 4 the palatal and pharyngeal musculature has three nerve innervations. It should be noted that FIG. 4 generally illustrates most if not all known innervations to the palatal and pharyngeal musculature but that no actual anatomic variant with all of these branching patterns would likely exist in a single patient. Normal anatomic variants may necessitate use of one or more different target sites in different patients to achieve desired stimulation of the palatal and pharyngeal musculature. In certain aspects and with reference to FIG. 4, a neuromodulation signal may be delivered to a target site proximate to a lesser palatine nerve (LPN). In other aspects, a neuromodulation signal may be delivered to a target site proximate to a lesser palatine nerve in such a fashion that its proximity to the tensor veli palatini (TVP) muscle simultaneously activates the tensor veli palatini muscle. In other aspects, a neuromodulation signal may be delivered to a target site proximate to a lesser palatine nerve in such a fashion that its proximity to the tensor veli palatini muscle simultaneously activates the tensor veli palatini muscle and/or fibres from the pharyngeal plexus (Pplex-X, Pplex-IX) branch to the palatopharyngeus (PP) muscle, and/or fibres from the pharyngeal plexus branch to the palatoglossus (PG) muscle, and/or to fibres from the pharyngeal plexus branch to the superior constrictor (SC) muscle, and/or to fibers from the pharyngeal plexus branch to the middle constrictor (MC) muscle, and/or fibers from the pharyngeal plexus branch to the levator veli palatini muscle (LVP) are also stimulated. In other aspects, a neuromodulation signal may be delivered to a target site proximate to a lesser palatine nerve in such a fashion that its proximity to fibers from the pharyngeal plexus branch to the palatopharyngeus muscle, and/or fibres from the pharyngeal plexus branch to the palatoglossus muscle, and/or to fibres from the pharyngeal plexus branch to the superior constrictor muscle, and/or to fibres from the pharyngeal plexus branch to the superior constrictor muscle, and/or fibres from the pharyngeal plexus branch to the levator veli palatini muscle are also stimulated. The foregoing are just a few examples of a target site for neuromodulation, however embodiments of the invention described hereafter are not necessarily limited to the above-described target sites.

[0079] With reference to FIG. 4, in other aspects, a neuromodulation signal may be delivered to a target site proximate to a lesser palatine nerve activating the palatal and pharyngeal musculature, and/or a neuromodulation signal may be delivered to a target site proximate to a nerve to tensor veli palatini activating the tensor veli palatini muscle. In other aspects, a neuromodulation signal may be delivered to a target site proximate to a lesser palatine nerve activating the palatal and pharyngeal musculature, and/or a neuromodulation signal may be delivered to a target site proximate to a nerve to tensor veli palatini activating a tensor veli palatini muscle and/or a neuromodulation signal may be delivered to a target site proximate to a tensor veli palatini muscle. In other aspects, a neuromodulation signal may be delivered to a target site proximate to a lesser palatine nerve activating the palatal and pharyngeal musculature, and/or a neuromodulation signal may be delivered to a target site proximate to a nerve to tensor veli palatini activating a tensor veli palatini muscle and/or a neuromodulation signal may be delivered to a target site proximate to a tensor veli palatini muscle, and/or a neuromodulation signal may be delivered to a target site proximate to a branch of a pharyngeal plexus to a palatopharyngeus and/or a palatoglossus muscle, and/or a superior constrictor muscle, and/or a middle constrictor muscle, and/or a levator veli palatini, and/or any combination therein. In other aspects, a neuromodulation signal may be delivered to a target site proximate to a lesser palatine nerve activating the palatal and pharyngeal musculature, and/or a neuromodulation signal may be delivered to a target site proximate to a nerve to tensor veli palatini activating a tensor veli palatini muscle and/or a neuromodulation signal may be delivered to a target site proximate to a branch of a pharyngeal plexus to a palatopharyngeus muscle and/or a palatoglossus muscle, and/or a superior constrictor muscle, and/or a middle constrictor muscle, and/or a levator veli palatini, or any combination therein. In other aspects, a neuromodulation signal may be delivered to a target site proximate to a lesser palatine nerve activating the palatal and pharyngeal musculature, and/or a neuromodulation signal may be delivered to a target site proximate to a tensor veli palatini muscle. In other aspects, a neuromodulation signal may be delivered to a target site proximate to a lesser palatine nerve activating the palatal and pharyngeal musculature, and/or a neuromodulation signal may be delivered to a target site proximate to a tensor veli palatini muscle and/or a neuromodulation signal may be delivered to a target site proximate to a branch of a pharyngeal plexus to a palatopharyngeus muscle and/or a palatoglossus muscle, and/or a superior constrictor muscle, and/or a middle constrictor muscle, and/or a levator veli palatini muscle, and/or any combination therein. In an embodiment a neuromodulation signal may be delivered to any of the nerve and muscle anatomy represented in FIG. 4 in any combination such that these nerves and muscles are activated, increasing their tone. The foregoing are just a few examples of a target site for neuromodulation, however embodiments of the present disclosure described hereafter are not necessarily limited to the above-described target sites. [0080] With reference to FIG. 5, the palatal and pharyngeal musculature consists of a levator veli palatini (LVP) muscle, a musculus uvulae (MU) muscle, a palatopharyngeus (PP) muscle, a palatoglossus muscle (PG) , a tensor veli palatini (TVP) muscle, a middle constrictor (MC) muscle and a superior constrictor (SC) muscle. In certain aspects and with reference to FIG. 5, a neuromodulation signal may be delivered to a target site proximate to a levator veli palatini muscle, and/or a musculus uvulae muscle, and/or a palatopharyngeus muscle, and/or a palatoglossus muscle, and/or a tensor veli palatini muscle, and/or a middle constrictor muscle, and/or a superior constrictor muscle and/or any combination therein. In other aspects, a neuromodulation signal may be delivered to a target site proximate to a levator veli palatini muscle, and/or a musculus uvulae muscle, and/or a palatopharyngeus muscle, and/or a palatoglossus muscle, and/or a tensor veli palatini muscle, and/or a middle constrictor muscle, and/or a superior constrictor muscle and/or any combination therein, such that its proximity to a lesser palatine nerve, and/or a pharyngeal plexus branch to a levator veli palatini, and/or a pharyngeal plexus branch to a palatoglossus, and/or a pharyngeal plexus branch to a palatopharyngeus, and/or a pharyngeal plexus branch to a superior constrictor, and/or a pharyngeal plexus branch to a middle constrictor, and/or a pharyngeal plexus branch to a levator veli palatini, and/or a nerve to tensor veli palatini, and/or any combination therein, such that these nerves may also be stimulated. In other aspects, a neuromodulation signal may be delivered to a target site proximate to a levator veli palatini muscle, and/or a musculus uvulae muscle, and/or a palatopharyngeus muscle, and/or a palatoglossus muscle, and/or a tensor veli palatini muscle, and/or a middle constrictor muscle, and/or a superior constrictor muscle and/or any combination therein such that its proximity to fibres of a lesser palatine nerve, and/or fibres of a pharyngeal plexus branch to a levator veli palatini, and/or a fibres of a pharyngeal plexus branch to a palatoglossus, and/or a fibres of a pharyngeal plexus branch to a palatopharyngeus, and/or a fibres of a pharyngeal plexus branch to a superior constrictor, and/or a fibres of a pharyngeal plexus branch to a middle constrictor, and/or a pharyngeal plexus branch to a levator veli palatini, and/or a fibres of a nerve to tensor veli palatini, and/or any combination therein, such that these nerve fibres may also be stimulated. In an embodiment a neuromodulation signal may be delivered to any of the nerve and muscle anatomy represented in FIG. 4 in any combination such that these nerves and muscles are activated, increasing their tone. The foregoing are just a few examples of a target site for neuromodulation, however embodiments of the invention described hereafter are not necessarily limited to the above-described target sites.

[0081] With reference to FIG. 6, in an aspect, a method 4 of treating sleep disordered breathing in a patient suffering therefrom comprises delivering a neuromodulation signal to a target site proximate to an intrinsic muscle of the tongue including a longitudinal muscle, and/or a transverse muscle, and/or a vertical muscle, and/or any combination therein. A target site can be proximate to an intrinsic muscle of the tongue including a longitudinal muscle, and/or a transverse muscle, and/or a vertical muscle and/or any combination therein such that delivering a neuromodulation signal activates the muscles fibres of these muscles thereby increasing their tone. Method 4 further comprises improving the patient’s sleep disordered breathing via delivery of the neuromodulation signal. In another aspect, a method 4 of treating sleep disordered breathing in a patient suffering therefrom comprises delivering a neuromodulation signal to a target site proximate to an extrinsic muscle of the tongue including a genioglossus muscle, and/or a hyoglossus muscle, and/or a styloglossus muscle, and/or any combination therein. A target site can be proximate to a genioglossus muscle, and/or a hyoglossus muscle, and/or a styloglossus muscle, and/or any combination therein such that delivering a neuromodulation signal activates the muscles fibers of these muscles thereby increasing their tone. Method 4 further comprises improving the patient’s sleep disordered breathing via delivery of the neuromodulation signal. In another aspect, a method 4 of treating sleep disordered breathing in a patient suffering therefrom comprises delivering a neuromodulation signal to a target site proximate to an intrinsic muscle of the tongue and/or an extrinsic muscle of the tongue including a longitudinal muscle, and/or a transverse muscle, and/or a vertical muscle, and/or a genioglossus muscle, and/or a hyoglossus muscle, and/or a styloglossus muscle, and/or any combination therein. A target site can be proximate to a longitudinal muscle, and/or a transverse muscle, and/or a vertical muscle, and/or a genioglossus muscle, and/or a hyoglossus muscle, and/or a styloglossus muscle, and/or any combination therein such that delivering a neuromodulation signal activates the muscles fibres of these muscles thereby increasing their tone. Method 4 further comprises improving the patient’s sleep disordered breathing via delivery of the neuromodulation signal. The foregoing are just a few examples of a method of neuromodulation, however embodiments of the invention described hereafter are not necessarily limited to the above-described methods.

[0082] With reference to FIG. 7, the tongue musculature consists of both intrinsic and extrinsic muscles. Intrinsic muscles include the superior longitudinal, inferior longitudinal, transverse and vertical muscles. Extrinsic muscles include the genioglossus, styloglossus, hyoglossus and palatoglossus muscles. In an aspect, a method 5 of treating sleep disordered breathing in a patient suffering therefrom comprises delivering a neuromodulation signal to a target site proximate to an intrinsic muscle of the tongue including a longitudinal muscle, and/or a transverse muscle, and/or a vertical muscle, and/or any combination therein. A target site can be proximate to an intrinsic muscle of the tongue including a longitudinal muscle, and/or a transverse muscle, and/or a vertical muscle and/or any combination therein such that delivering a neuromodulation signal activates the muscles fibers of these muscles thereby increasing their tone. Method 5 further comprises improving the patient’s sleep disordered breathing via delivery of the neuromodulation signal. In another aspect, a method 5 of treating sleep disordered breathing in a patient suffering therefrom comprises delivering a neuromodulation signal to a target site proximate to an extrinsic muscle of the tongue including a genioglossus muscle, and/or a hyoglossus muscle, and/or a styloglossus muscle, and/or any combination therein. A target site can be proximate to a genioglossus muscle, and/or a hyoglossus muscle, and/or a styloglossus muscle, and/or any combination therein such that delivering a neuromodulation signal activates the muscles fibers of these muscles thereby increasing their tone. Method 5 further comprises improving the patient’s sleep disordered breathing via delivery of the neuromodulation signal. In another aspect, a method 5 of treating sleep disordered breathing in a patient suffering therefrom comprises delivering a neuromodulation signal to a target site proximate to an intrinsic muscle of the tongue and/or an extrinsic muscle of the tongue including a longitudinal muscle, and/or a transverse muscle, and/or a vertical muscle, and/or a genioglossus muscle, and/or a hyoglossus muscle, and/or a styloglossus muscle, and/or any combination therein. A target site can be proximate to a longitudinal muscle, and/or a transverse muscle, and/or a vertical muscle, and/or a genioglossus muscle, and/or a hyoglossus muscle, and/or a styloglossus muscle, and/or any combination therein such that delivering a neuromodulation signal activates the muscles fibers of these muscles thereby increasing their tone. Method 5 further comprises improving the patient’s sleep disordered breathing via delivery of the neuromodulation signal. The foregoing are just a few examples of a target site for neuromodulation, however embodiments of the invention described hereafter are not necessarily limited to the above-described target sites.

[0083] With reference to FIG. 8, in an aspect, a method 6 of treating sleep disordered breathing in a patient suffering therefrom comprises delivering a neuromodulation signal to a target site proximate to a lesser palatine nerve and/or nerve to tensor veli palatini and/or pharyngeal plexus branches to a levator veli palatini, and/or a palatopharyngeus, and/or a palatoglossus, and/or a middle constrictor, and/or superior constrictor, and/or any combination therein that innervates the palatal and/or pharyngeal musculature, and/or delivering a neuromodulation signal to a target site proximate to a hypoglossal nerve that innervates a genioglossus muscle, and/or an ansa cervicalis nerve that innervates a strap muscle, and/ or any combination therein. A target site can be proximate to a lesser palatine nerve and/or nerve to tensor veli palatini and/or pharyngeal plexus branches to a levator veli palatini, and/or a palatopharyngeus, and/or a palatoglossus, and/or a middle constrictor, and/or superior constrictor, and/or any combination therein that innervates the palatal and/or pharyngeal musculature, and/or delivering a neuromodulation signal to a target site proximate to a hypoglossal nerve that innervates a genioglossus muscle, and/or an ansa cervicalis nerve that innervates a strap muscle, and/ or any combination therein such that delivering a neuromodulation signal activates the motor fibres of these nerves. Method 6 further comprises improving the patient’s sleep disordered breathing via delivery of the neuromodulation signal. Method 6 further includes activating a levator veli palatini muscle and/or musculus uvulae muscle and/or palatopharyngeus muscle and/or palatoglossus muscle and/or tensor veli palatini muscle and/or middle constrictor muscle and/or superior constrictor muscle, and/or a genioglossus muscle, and/or a strap muscle, and/or any combination therein. The foregoing are just a few examples of a method of neuromodulation, however embodiments of the invention described hereafter are not necessarily limited to the above-described methods.

[0084] In an aspect, a method for improving sleep disordered breathing in a patient suffering therefrom comprises of delivering a neuromodulation signal (such as an electrical or magnetic or ultrasound or piezoelectric or radiation signal or electromagnetic signal or radiofrequency or mechanical or chemical or optical or sound signal or any other signal, and/or any combination therein) to a target site of a hypoglossal nerve, an ansa cervicalis nerve, a branch of the pharyngeal plexus to the palatopharyngeus muscle, a branch of the pharyngeal plexus to the middle constrictor muscle, a sternothyroid muscle, a thyrohyoid muscle, an omohyoid muscle, a sternohyoid muscle, and/or any combination therein, in order to improve the patient’s sleep disordered breathing. [0085] With reference to FIG. 9, in an aspect, a method 7 of treating sleep disordered breathing in a patient suffering therefrom comprises delivering a neuromodulation signal to a target site proximate to a levator veli palatini, and/or a musculus uvulae, and/or a palatopharyngeus, and/or a palatoglossus, and/or a middle constrictor, and/or superior constrictor, and/or any combination therein, and/or delivering a neuromodulation signal to a target site proximate to a hypoglossal nerve that innervates a genioglossus muscle, and/or an ansa cervicalis nerve that innervates a strap muscle, and/ or any combination therein. A target site can be proximate to a levator veli palatini, and/or a musculus uvulae, and/or a palatopharyngeus, and/or a palatoglossus, and/or a middle constrictor, and/or superior constrictor, and/or a hypoglossal nerve that innervates a genioglossus muscle, and/or an ansa cervicalis nerve that innervates a strap muscle, and/ or any combination therein such that delivering a neuromodulation signal activates these muscles. Method 7 further comprises improving the patient’s sleep disordered breathing via delivery of the neuromodulation signal. Method 7 further includes activating a levator veli palatini muscle and/or musculus uvulae muscle and/or palatopharyngeus muscle and/or palatoglossus muscle and/or tensor veli palatini muscle and/or middle constrictor muscle and/or superior constrictor muscle, and/or a genioglossus muscle, and/or a strap muscle, and/or any combination therein. The foregoing are just a few examples of a method of neuromodulation, however embodiments of the invention described hereafter are not necessarily limited to the above-described methods.

[0086] With reference to FIG. 10, in an aspect, a method 8 of treating sleep disordered breathing in a patient suffering therefrom comprises delivering a neuromodulation signal to a target site proximate to a lesser palatine nerve and/or nerve to tensor veli palatini and/or pharyngeal plexus branches to levator veli palatini, palatopharyngeus, palatoglossus, middle constrictor and/or superior constrictor and/or any combination therein that innervates the palatal and/or pharyngeal musculature, and/or any combination therein, and/or a target site proximate to a levator veli palatini muscle and/or musculus uvulae muscle and/or palatopharyngeus muscle and/or palatoglossus muscle and/or tensor veli palatini muscle and/or middle constrictor muscle and/or superior constrictor muscle and/or any combination therein, and/or a target site proximate to an intrinsic muscle of the tongue and/or an extrinsic muscle of the tongue including a longitudinal muscle, and/or a transverse muscle, and/or a vertical muscle, and/or a genioglossus muscle, and/or a hyoglossus muscle, and/or a styloglossus muscle, and/or any combination therein such that delivering a neuromodulation signal activates the motor fibres of these nerves and activates the muscle fibres of these muscles thereby increasing their tone. A target site can be proximate to a lesser palatine nerve and/or nerve to tensor veli palatini and/or pharyngeal plexus branches to levator veli palatini, palatopharyngeus, palatoglossus, middle constrictor and/or superior constrictor and/or any combination therein, and/or a levator veli palatini muscle and/or musculus uvulae muscle and/or palatopharyngeus muscle and/or palatoglossus muscle and/or tensor veli palatini muscle and/or middle constrictor muscle and/or superior constrictor muscle and/or any combination therein, and/or a target site proximate to an intrinsic muscle of the tongue and/or an extrinsic muscle of the tongue including a longitudinal muscle, and/or a transverse muscle, and/or a vertical muscle, and/or a genioglossus muscle, and/or a hyoglossus muscle, and/or a styloglossus muscle, and/or any combination therein such that delivering a neuromodulation signal activates the motor fibres of these nerves and activates the muscle fibres of these muscles thereby increasing their tone. Method 8 further comprises improving the patient’s sleep disordered breathing via delivery of the neuromodulation signal. The foregoing are just a few examples of a method of neuromodulation, however embodiments of the invention described hereafter are not necessarily limited to the above-described methods.

[0087] With reference to FIG. 11, in an aspect, a method 9 of treating sleep disordered breathing in a patient suffering therefrom comprises delivering a neuromodulation signal to a target site proximate to a lesser palatine nerve and/or nerve to tensor veli palatini and/or pharyngeal plexus branches to levator veli palatini, palatopharyngeus, palatoglossus, middle constrictor and/or superior constrictor and/or any combination therein that innervates the palatal and/or pharyngeal musculature, and/or any combination therein, and/or a target site proximate to a levator veli palatini muscle and/or musculus uvulae muscle and/or palatopharyngeus muscle and/or palatoglossus muscle and/or tensor veli palatini muscle and/or middle constrictor muscle and/or superior constrictor muscle and/or any combination therein, and/or a target site proximate to a hypoglossal nerve that innervates a genioglossus muscle, and/or an ansa cervicalis nerve that innervates a strap muscle, and/ or any combination therein such that delivering a neuromodulation signal activates the motor fibres of these nerves and activates the muscle fibres of these muscles thereby increasing their tone. A target site can be proximate to a lesser palatine nerve and/or nerve to tensor veli palatini and/or pharyngeal plexus branches to levator veli palatini, palatopharyngeus, palatoglossus, middle constrictor and/or superior constrictor and/or any combination therein, and/or a levator veli palatini muscle and/or musculus uvulae muscle and/or palatopharyngeus muscle and/or palatoglossus muscle and/or tensor veli palatini muscle and/or middle constrictor muscle and/or superior constrictor muscle and/or any combination therein, and/or a target site proximate to a hypoglossal nerve that innervates a genioglossus muscle, and/or an ansa cervicalis nerve that innervates a strap muscle, and/ or any combination therein such that delivering a neuromodulation signal activates the motor fibres of these nerves and activates the muscle fibres of these muscles thereby increasing their tone. Method 9 further comprises improving the patient’s sleep disordered breathing via delivery of the neuromodulation signal. The foregoing are just a few examples of a method of neuromodulation, however embodiments of the invention described hereafter are not necessarily limited to the above-described methods.

[0088] With reference to FIG. 12, in an aspect, a method 10 of treating sleep disordered breathing in a patient suffering therefrom comprises delivering a neuromodulation signal to a target site proximate to a to a lesser palatine nerve and/or nerve to tensor veli palatini and/or pharyngeal plexus branches to levator veli palatini, palatopharyngeus, palatoglossus, middle constrictor and/or superior constrictor and/or any combination therein that innervates the palatal and/or pharyngeal musculature, and/or any combination therein, and/or a target site proximate to a levator veli palatini muscle and/or musculus uvulae muscle and/or palatopharyngeus muscle and/or palatoglossus muscle and/or tensor veli palatini muscle and/or middle constrictor muscle and/or superior constrictor muscle and/or any combination therein, and/or a target site proximate to an intrinsic muscle of the tongue and/or an extrinsic muscle of the tongue including a longitudinal muscle, and/or a transverse muscle, and/or a vertical muscle, and/or a genioglossus muscle, and/or a hyoglossus muscle, and/or a styloglossus muscle, and/or any combination therein, and/or a target site proximate to a hypoglossal nerve that innervates a genioglossus muscle, and/or an ansa cervicalis nerve that innervates a strap muscle, and/ or any combination therein such that delivering a neuromodulation signal activates the motor fibres of these nerves and activates the muscle fibres of these muscles thereby increasing their tone. A target site can be proximate to a lesser palatine nerve and/or nerve to tensor veli palatini and/or pharyngeal plexus branches to levator veli palatini, palatopharyngeus, palatoglossus, middle constrictor and/or superior constrictor and/or any combination therein, and/or a levator veli palatini muscle and/or musculus uvulae muscle and/or palatopharyngeus muscle and/or palatoglossus muscle and/or tensor veli palatini muscle and/or middle constrictor muscle and/or superior constrictor muscle and/or any combination therein, and/or a target site proximate to an intrinsic muscle of the tongue and/or an extrinsic muscle of the tongue including a longitudinal muscle, and/or a transverse muscle, and/or a vertical muscle, and/or a genioglossus muscle, and/or a hyoglossus muscle, and/or a styloglossus muscle, and/or any combination therein, and/or a target site proximate to a hypoglossal nerve that innervates a genioglossus muscle, and/or an ansa cervicalis nerve that innervates a strap muscle, and/ or any combination therein such that delivering a neuromodulation signal activates the motor fibres of these nerves and activates the muscle fibres of these muscles thereby increasing their tone. Method 10 further comprises improving the patient’s sleep disordered breathing via delivery of the neuromodulation signal. The foregoing are just a few examples of a method of neuromodulation, however embodiments of the invention described hereafter are not necessarily limited to the above-described methods.

[0089] With reference to FIG. 13, in an embodiment, a neurostimulation system includes at least one electrode, a pulse generator, a battery, an oral appliance, a charger, and a remote. In this embodiment, an oral appliance subsystem consists of at least one electrode, a pulse generator, a battery, and a feature to allow the oral appliance to secure to a position within the oral cavity. In this embodiment, a charger and remote are encapsulated as another subsystem. In this embodiment, a charger powers a battery within the oral appliance. The battery powers the pulse generator which is activated and transmits an electrical or other impulse to at least one electrode based on neurostimulation parameters controlled by the remote. This neurostimulation signal is transmitted to the affected anatomical targets via the electrode(s). In this embodiment the electrode may consist of one or more electrodes on each side of the oral appliance to deliver the neurostimulation signal. The foregoing are just a few examples of an embodiment of a neurostimulation system, however embodiments of the invention described hereafter are not necessarily limited to the above-described embodiments.

[0090] With reference to FIG. 14, in an embodiment, a neurostimulation system includes at least one electrode, an antenna, a pulse generator, a rechargeable battery cell, an oral appliance, a charger, and a remote. In this embodiment, an implanted electrode subsystem consists of one or more electrodes and an antenna or signal receiver to receive a wired or wireless signal. There may be one or more implanted electrode subsystems in the full neurostimulation system. In this embodiment, an oral appliance subsystem consists of a pulse generator, a battery, and a feature to allow the oral appliance to secure to a position within the oral cavity. In this embodiment, a charger and remote are encapsulated as another subsystem. In this embodiment, a charger powers a battery within the oral appliance. The battery powers the pulse generator which is activated and transmits a signal and power to the implanted electrode subsystem(s) based on neurostimulation parameters controlled by the remote. This neurostimulation signal is transmitted to the affected anatomical targets via the electrode(s). In this embodiment the implanted electrode subsystems may be implanted using a delivery system multiple anatomical locations on either side of the oral cavity to deliver the neurostimulation signal to the anatomical targets. The foregoing are just a few examples of an embodiment of a neurostimulation system, however embodiments of the invention described hereafter are not necessarily limited to the above-described embodiments.

[0091] With reference to FIGS. 15, 16A, and 16B, the oral appliance subsystem can be a wearable device including molding to the upper palate, molding to the mandible, fit to dentition, mechanical attachment to craniofacial anatomy, such as wiring in one embodiment, mechanical attachment to oral, pharyngeal or nasal mucosa, adhesion to the oral mucosa, and/or another attachment feature(s) for securing the oral appliance to the patient in proximity to the targeted anatomy such as in an embodiment the lesser palatine nerve and/or nerve to tensor veli palatini, and/or a pharyngeal plexus branch to a levator veli palatini, palatopharyngeus, palatoglossus, middle constrictor and/or superior constrictor. In an embodiment where there is an implantable receiver in communication with one or more implanted electrodes comprising the neurostimulator subsystem, an oral appliance subsystem can include a programmable pulse generator unit for transmitting power, for example inductive power transmission, radiofrequency power transmission, or ultrasound power transmission among others, from the oral appliance subsystem to the implanted neurostimulator. In this embodiment, the implantable neurostimulator may be delivered through a permucosal/transmucosal and/or percutaneous delivery system consisting of deployment via a catheter, cannula, sheath, and/or other conduit, through an injection, and/or through surgical placement and/or any other method of delivery. In this embodiment, a rechargeable battery in the oral appliance subsystem may be powered prior to use through wired or inductive energy transfer from a charging case and remote subsystem. In this embodiment, the case and remote subsystem also may function as a programming device that may be used to initiate terminate, and modulate therapy delivered by the oral appliance and neurostimulator subsystems via a bidirectional wired or wireless telemetry link.

[0092] With reference to FIGS. 15, 16A, and 16B, in another embodiment where an oral appliance subsystem can consist of one or more electrodes, a programmable pulse generator, and a rechargeable battery. In this embodiment, the one or more electrodes may be configured to independently target sites including a lesser palatine nerve, and/or nerve to tensor veli palatini, and/or a pharyngeal plexus branch to a levator veli palatini, palatopharyngeus, palatoglossus, middle constrictor and/or superior constrictor, and/or any combination therein. Additionally, electrodes may be configured in an array to target a lesser palatine nerve, and/or nerve to tensor veli palatini, and/or a pharyngeal plexus branch to a levator veli palatini, palatopharyngeus, palatoglossus, middle constrictor and/or superior constrictor, and/or any combination therein. Additionally, electrodes may be configured in an array to target a levator veli palatini, a tensor veli palatini, a palatopharyngeus, palatoglossus, middle constrictor, superior constrictor, and/or any combination therein. Additionally, at least one electrode may be configured in an array to target an aforementioned nerve innervating a palatal or pharyngeal muscle, and/or an aforementioned palatal or pharyngal muscle, and/or any combination therein. In this embodiment, the rechargeable battery in the oral appliance subsystem may be powered prior to use through wired or inductive energy transfer from a charging case and remote subsystem. In this embodiment, the case and remote subsystem also may function as a programming device that may be used to initiate terminate, and modulate therapy delivered by the oral appliance pulse generator via a bidirectional wired or wireless telemetry link. The foregoing are just a few examples of an embodiment of a neurostimulation system, however embodiments of the invention described hereafter are not necessarily limited to the above-described embodiments.

[0093] With reference to FIG. 17, the charging case and remote subsystem consists of charging pads (tightly coupled electromagnetic resonant inductive or non-radiative charging) and/or charging bowls (loosely coupled or radiative electromagnetic resonant charging) and/or uncoupled radio frequency (RF) wireless charging and/or any combination therein to transfer energy from the charging case and remote subsystem to the oral appliance subsystem while the oral appliance subsystem is docked within and/or on top of and/or proximal to the electromagnetic field of the charging case and remote subsystem. The case and remote subsystem also may function as a programming device that may be used to initiate, terminate, regulate, optimize and/or modulate therapy delivered by the oral appliance and neurostimulator subsystems via a bidirectional wired or wireless telemetry link. In an embodiment, a closed-loop system consists of sensing and/or measuring and/or monitoring of physiologic parameters and or/surrogates for sleep and/or sleep apnea and/or breathing, either processing data from those parameters and/or surrogates or directly controlling neurostimulation and communicating a signal to electrodes for stimulation of target anatomy. In this embodiment, the processing of these parameters may either be performed by a processor located in the oral appliance subsystem or in a processor located in the charging case and remote subsystem. In this embodiment, data may be transferred to/from the oral appliance subsystem and the charging case and remote subsystem through a bidirectional wired or wireless telemetry link. This data may be stored in either the oral appliance subsystem and/or charging case and remote subsystem and may be accessed by a patient and/or physician and/or surgeon and/or dentist and/or nurse and/or health practitioner and/or any combination therein to track and/or view and/or titrate and/or regulate and/or modulate and/or optimize the neurostimulation parameters and/or usage data and/or compliance data and/or physiologic parameters and or/surrogates for sleep and/or sleep apnea and/or breathing. In another embodiment, an open-loop system consists of configuration of neurostimulation parameters based upon polysomnographic data and/or data from a home sleep study and/or data from another form of sleep study and/or data from an anatomical assessment such as a radiological examination and/or an endoscopic examination and/or a drug induced endoscopic examination and/or an awake endoscopic examination and/or a laboratory examination and/or physiologic examination and/or any technological examination and/or any aforementioned examination, and/or any combination therein. In this embodiment, data may be transferred to/from the oral appliance subsystem and the charging case and remote subsystem through a bidirectional wired or wireless telemetry link. This data may be stored in either the oral appliance subsystem and/or charging case and remote subsystem and may be accessed by a patient and/or physician and/or surgeon and/or dentist and/or nurse and/or health practitioner and/or any combination therein to track and/or view and/or titrate and/or regulate and/or modulate and/or optimize the neurostimulation parameters and/or usage data and/or compliance data and/or physiologic parameters and or/surrogates for sleep and/or sleep apnea and/or breathing. In this embodiment, neurostimulation parameters may be titrated and/or modulated and/or regulated and/or optimized by a patient and/or physician and/or surgeon and/or dentist and/or nurse and/or health practitioner and/or any combination therein to deliver custom neurostimulation therapy for each patient through a bidirectional wired or wireless telemetry link.

[0094] A device according to some embodiments may include at least a housing configured to location on a body of a subject proximate to a lesser palatine nerve or upper airway muscle. The primary power source may be rechargeable and associated with the housing and/or configured within the housing. The device may additionally include at least one processor associated with the housing and configured for electrical or other communication with a power source. The at least one processor may be further configured to regulate the delivered power by adjusting at least one of current amplitude, voltage amplitude, frequency, pulse width, duty cycle, pulse configuration and/or any combination therein [0095] In an embodiment, neuromodulation may be delivered with varying modulation parameters according to the patient’s sleep disordered breathing characteristics. In an embodiment, the neuromodulation signal may be an electrical or magnetic or ultrasound or piezoelectric or radiation signal or electromagnetic signal or radiofrequency or mechanical or chemical or optical or sound signal or any other signal, and/or any combination therein. In an embodiment, the signal delivered may be delivered continuously and/or in successive pulse trains. Such continuous signals and pulse trains may be in the form of square waves, sine waves, triangle waves, exponential waves, sawtooth waves, pulse waves, an arbitrary waveform, and/or any combination therein. Such pulse trains may be in the waveform of monophasic or biphasic, symmetric or asymmetrical, and/or any combination therein. Pulse trains may be delivered in repeated bursts in the range of 1 pulse per train to 1,000,000 pulses per train. Pulse trains may be delivered in intervals of 0.01 microseconds with a range of 0.01 microseconds to 600 seconds. Each burst may be delivered in a plurality of parameters including current amplitudes, voltage amplitudes, frequencies, pulse widths, duty cycles, pulse configurations and/or any combination therein. Such current amplitudes may be delivered in the range of 0.01mA to 1A, these parameters are exemplary only, and may be adjusted above or below the ranges given to achieve suitable results. Such voltage amplitudes may be delivered in the range of 0.0 IV to 250V, these parameters are exemplary only, and may be adjusted above or below the ranges given to achieve suitable results. Such frequencies may be delivered in the range of 0.01Hz to 10kHz, these parameters are exemplary only, and may be adjusted above or below the ranges given to achieve suitable results. Such pulse widths may be delivered in the range of 0.01 Ds to 600s, these parameters are exemplary only, and may be adjusted above or below the ranges given to achieve suitable results. Such duty cycles may be delivered in the range of 0% to 100%, these parameters are exemplary only, and may be adjusted above or below the ranges given to achieve suitable results. Such pulse configurations may be delivered in any configuration to achieve suitable results, including voltage amplitude ramp-up, current amplitude ramp up, voltage amplitude step-down, current amplitude stepdown, variable pulse widths, variable duty cycles, variable current amplitudes, variable voltage amplitudes, sine-wave configurations, square-wave configurations, triangle wave configuration, exponential wave configurations, sawtooth wave configurations, pulse wave configurations, arbitrary wave configurations, in temporal patterns, in temporal sequences, in random patterns, in random sequences, and/or any combination therein. Such amplitude ramps can be configured in intervals of 0.01 microseconds in the range of 0.0 to 600 seconds, these parameters are exemplary only, and may be adjusted above or below the ranges given to achieve suitable results. In an embodiment, neuromodulation may be delivered with varying modulation parameters according to the disease being treated or monitored within or above or below the aforementioned ranges. Such pulse trains may be initiated immediately at inspiration or before inspiration or during inspiration or after inspiration in order to achieve improved of the patient’s sleep disordered breathing. Such frequencies may be delivered according to the nerve characteristic or type or anatomy and intended treatment outcomes, including, to preferentially or selectively modulate motor fibres or sensory fibers or parasympathetic fibers or sympathetic fibers or any nerve fiber and/or any combination therein in order to treat conditions affected by modulation of these fibers. Such pulse widths may be delivered according to the nerve characteristic or type or anatomy and intended treatment outcomes, including, to preferentially or selectively modulate motor fibres or sensory fibers or parasympathetic fibers or sympathetic fibers or any nerve fiber and/or any combination therein in order to treat conditions affected by modulation of these fibers. Such current amplitudes may be delivered according to the nerve characteristic or type or anatomy and intended treatment outcomes, including, to preferentially or selectively modulate motor fibres or sensory fibers or parasympathetic fibers or sympathetic fibers or any nerve fiber and/or any combination therein in order to treat conditions affected by modulation of these fibers. Such voltage amplitudes may be delivered according to the nerve characteristic or type or anatomy and intended treatment outcomes, including, to preferentially or selectively modulate motor fibres or sensory fibers or parasympathetic fibers or sympathetic fibers or any nerve fiber and/or any combination therein in order to treat conditions affected by modulation of these fibers. Such duty cycles may be delivered according to the nerve characteristic or type or anatomy and intended treatment outcomes, including, to preferentially or selectively modulate motor fibres or sensory fibers or parasympathetic fibers or sympathetic fibers or any nerve fiber and/or any combination therein in order to treat conditions affected by modulation of these fibers. Such pulse configurations may be delivered according to the nerve characteristic or type or anatomy and intended treatment outcomes, including, to preferentially or selectively modulate motor fibres or sensory fibers or parasympathetic fibers or sympathetic fibers or any nerve fiber and/or any combination therein in order to treat conditions affected by modulation of these fibers. Such pulse trains, frequencies, pulse widths, current amplitudes, voltage amplitudes, duty cycles, pulse configurations and any other modulation parameter may be delivered non-selectively and/or in any combination in order to treat conditions affected by modulation of these fibers. Such parameters are exemplary only, and may be adjusted above or below the ranges given to achieve suitable results. [0096] Without wishing to be bound by a particular embodiment, a method and system for treating sleep disordered breathing, may be designed, manufactured, built, constructed, formed, assembled, shaped, molded, fabricated or produced such that electrodes are placed according to specific patient anatomy in order to achieve airway opening and optimal improvement in a patient’s sleep disordered breathing. For example, where anteroposterior palatal collapse is identified as the primary mechanism of airway collapse in a patient, the electrodes may be placed in the delivery system to preferentially, globally or incombination with other anatomical mechanisms and/or neuromodulation, activate the palatoglossus and levator veli palatini muscles, in order to produce anterior movement of the palate, in order to relieve anteroposterior palatal obstruction and produce airway opening. The electrodes may be placed in contact with the mucosa overlying the desired neuromodulation target in order to modulate underlying nerves and muscles in order to produce activation of the desired nerve and/or muscle in order to produce airway opening in order to improve the patient’s sleep disordered breathing. One or more electrodes passing neuromodulation signals may be placed from 0mm to 30cm from each other in order to achieve activation of a target nerve and/or muscle, and/or to achieve partial or complete or tetanic or sub-tetanic activation of a desired nerve and/or muscle target. In an embodiment, an electrode may be placed at the extremes of a muscle length in order to produce activation of the entire length of that muscle in order to produce maximal airway opening and improvement of a patient’s sleep disordered breathing. For example, electrodes may placed in any delivery system on the maxillary surface of the teeth and/or hard palate, and/or soft palate, and/or oral cavity with a receiving electrode in a separate or conjoined delivery system on the retromolar trigone and/or mandibular teeth, and/or floor of mouth, and/or bone, and/or mandible, and/or submandibular region, and/or internal neck, and/or external surface of the neck, and/or inferior insertion and/or middle substance and/or any component of a palatoglossus muscle and/or palatopharyngeal muscle and/or superior constrictor muscle and/or middle constrictor muscle and/or intrinsic tongue muscle (such as a superior longitudinal muscle, or inferior longitudinal muscle, or transverse muscle or vertical muscle) and/or extrinsic tongue muscle (such as a genioglossus or hyoglossus or styloglossus muscle, and/or any combination therein), and/or strap muscle (such as a sternothyroid muscle, and/or a thyrohyoid muscle, and/or a omohyoid muscle, and/or a sternohyoid muscle, and/or any combination therein) and/or masseter muscle such that the neuromodulation signal passes to and/or through the nerve and/or muscle and produces activation of that muscle in order to produce airway opening and improvement of a patient’s sleep disordered breathing. For example and with reference to FIG. 18 an electrode may be placed at the superomedial insertion of the palatoglossus muscle to the palatine aponeurosis in a retainer and a receiving electrode placed on the retromolar trigone such that the neuromodulation signal may be sent along the length of the palatoglossus muscle. In another embodiment and with reference to FIG. 18, an electrode may be placed at the superomedial insertion of the palatoglossus muscle to the palatine aponeurosis in a retainer and a receiving electrode placed on a device component placed over the third molar tooth such that the neuromodulation signal may be sent along the length of the palatoglossus muscle to a fixed point secured on a mandibular tooth. In this embodiment, a non-conductive coating or material may be in contact with the tooth and the receiving electrode embedded into the non-conductive coating or material in order to prevent modulation of dental pulp nerves, the inferior alveolar nerve or any nerve that is not intended to be modulated. In another embodiment and with reference to FIG. 18, an electrode may be placed at the superomedial insertion of the palatoglossus muscle to the palatine aponeurosis in a retainer and a receiving electrode placed on at the glossal insertion of the palatoglossus such that the neuromodulation signal may be sent along the length of the palatoglossus muscle. In another embodiment and with reference to FIG. 19, an electrode may be placed in a retainer at in any arrangement or array or distribution or position relative to a muscle that is intended to be activated and a receiving electrode placed in any arrangement or array or distribution or position relative to a muscle that is intended to be activated such that the neuromodulation signal may be sent along the length of the those muscles, in order to activate those muscles. For example, an electrode may be positioned at the lateral aspects of the musculus uvulae muscle in order to send a neuromodulation signal across that muscle in order to activate that muscle and produce an airway opening effect. These electrodes may be placed in any orientation that affords capture of the nerve and/or muscle of interest, for example vertically or horizontally. In another embodiment and with reference to FIG. 19, electrode combinations may be placed submucosally proximate to a nerve and/or muscle target in any arrangement or array or distribution or position relative to a muscle that is intended to be activated and a receiving electrode placed in any arrangement or array or distribution or position relative to a muscle that is intended to be activated such that the neuromodulation signal may be sent along the length of the those muscles, in order to activate those muscles selectively or in combination as is desired to produce airway opening and improve a patient’s sleep disordered breathing. In an embodiment, and with reference to FIG. 20, an array of electrodes may be placed in the retainer proximate to a nerve and/or muscle target in order to deliver a wide or a narrow field in order to activate one or more muscles in that field selectively or in combination as is desired to produce airway opening and improve a patient’s sleep disordered breathing. In another embodiment and with reference to FIG. 20, electrode arrays may be placed submucosally and/or subcutaneously and/or intramuscular and/or perimuscular and/or proximate to any nerve and/or muscle target in order to deliver a wide or a narrow field in order to activate one or more muscles in that field selectively or in combination as is desired to produce airway opening and improve a patient’s sleep disordered breathing. For example, and with reference to FIG. 21, one or more electrodes and/or an electrode array may be placed submucosally and/or subcutaneously and/or intramuscular and/or perimuscular and/or proximate to the supermedial insertion of a palatopharyngeus and/or palatoglossus muscle and the inferior insertion of these muscles in order to activate a nerve and/or muscle, produce airway opening and improve a patient’s sleep disordered breathing. In all embodiments herein, neuromodulation signals may be passed in one or more directions in order to activate a nerve and/or muscle, produce airway opening and improve a patient’s sleep disordered breathing. In all embodiments herein, one or more electrodes and/or electrode arrays may be placed in any anatomical position and/or positions to afford maximal modulation of a target nerve and/or nerves and/or muscle and/or muscles in a therapy delivery system and/or device and/or appliance and/or retainer, and/or a non-invasive method and/or procedure, and/or an invasive method and/or procedure, and/or an implant, and/or a non-implant form in order to produce airway opening in order to improve a patient’s sleep disordered breathing. The foregoing are just a few examples of a therapy delivery system for sleep disordered breathing, however embodiments of the invention described hereafter are not necessarily limited to the above-described. [0097] In an embodiment, a physician and/or surgeon and/or dentist and/or nurse and/or health practitioner and/or any combination therein may select electrode positioning to target a nerve and/or nerves and/or muscle and/or muscles according to a patient’s anatomical and/or physiological characteristics in order to treat a patient’s sleep disordered breathing and/or optimize and/or titrate therapy and/or its effects. A physician and/or surgeon and/or dentist and/or nurse and/or health practitioner and/or any combination therein, may utilize anatomical data for this purpose from a clinical examination including an oral cavity examination, and/or a nasal examination, and/or a nasopharyngeal examination, and/or an oropharyngeal examination, and/or a hypopharyngeal examination and/or a laryngeal examination and/or a tongue examination, and/or a tongue base examination, and or a supraglottic examination, and/or a glottic examination, and/or subglottic examination, and/or an endoscopic and/or non-endoscopic examination of the oral cavity/ and or nasal cavity and/or nasopharynx and/or oropharynx and/or hypopharynx and/or tongue and/or tongue base and/or larynx, and/or supraglottis and/or glottis and/or subglottis, a neck examination, a craniofacial examination, a facial bone examination, an airway examination, a dental examination, and/or a radiological examination, and/or an endoscopic examination, and/or a drug induced endoscopic examination, and/or an awake endoscopic examination, and/or a laboratory examination, and/or physiologic examination, and/or any technological examination, and/or any aforementioned examination, and/or any other method used to screen for and/or diagnose sleep disordered breathing, and/or any method, and/or any combination therein. A physician and/or surgeon and/or dentist and/or nurse and/or health practitioner and/or any combination therein, may utilize physiological data for this purpose from a clinical examination, and/or a polysomnographic examination, and/or any aforementioned examination type and/or any combination therein for this purpose. The foregoing are just a few examples of a therapy delivery system for sleep disordered breathing, however embodiments of the invention described hereafter are not necessarily limited to the above-described. [0098] In an embodiment a sensing modality embedded into the device intended to improve a patient’s sleep disordered breathing may be utilized to gain data in order to inform a healthcare provider (including a physician and/or surgeon and/or dentist and/or nurse and/or health practitioner and/or any combination therein) of the efficacy, and/or effectiveness, and/or compliance, and/or adherence, and/or disease improvement, and/or symptomatic improvement, and/or quality of life improvement, and/or daytime function improvement, and/or sleep quality improvement, and/or any aforementioned health, and/or wellness metric, and/or any combination therein. In an embodiment, a healthcare provider (including a physician and/or surgeon and/or dentist and/or nurse and/or health practitioner and/or any combination therein) may use this data to optimize and/or titrate and/or monitor therapy and/or any combination therein. Data gained from these examinations and/or modalities include data pertaining to airway volume, and/or airway obstruction, and/or airway patency, and/or critical closing pressure of the pharynx and/or palate, and/or increase in a pharyngeal and/or palatal opening pressure, and/or airway tissue collapsibility, and/or airway muscle collapsibility, and/or pharyngeal airflow, and/or lung ventilation, and/or presence and/or frequency of apnea, and/or frequency and/or presence of hypopnea, and/or apnea-hypopnea index, and/or oxygen desaturation index, and/or lowest oxygen saturation, and/or hypoxic time, and/or relative hypoxic time, and/or hypercarbia and/or hypercapnia, and/or sleep quality, and/or sleep efficiency, and/or sleep quality, and/or daytime sleepiness, and/or snoring, and/or arousal frequency, and/or total sleep time, and/or wakefulness after sleep onset, and/or stage of sleep, and/or REM sleep, and/or non-REM sleep, and/or REM latency, and/or central apnea frequency, and/or mixed apnea presence and/or frequency, and/or number of respiratory events, and/or supine respiratory events, and/or lateral respiratory events, and/or prone respiratory events, and/or any sleep quality metric, and/or any sleep disturbance, and/or any sleep disorder, and/or cardiovascular risk, and/or cerebrovascular risk, and/or metabolic risk, and/or sleep onset latency, and/or respiratory effort related arousal, and/or circadian function, and/or any polysomnographic parameter, and/or any non-polysomnographic parameter, and/or any sleep quality metric, and/or nasal function, and/or sinus function, and/or sinonasal function, and/or any health benefit, and/or any combination therein. Data gained from this device may include oxygen saturation, respiratory rate and/or rhythm and/or regularity and/or irregularity and/or pattern and/or variability, airflow data including nasal and/or nasopharyngeal and/or oropharyngeal and/or oral cavity and/or hypopharyngeal and/or laryngeal and/or glottic and/or supraglottic and/or subglottic and/or external airflow, pressure data including nasal and/or nasopharyngeal and/or oropharyngeal and/or oral cavity and/or hypopharyngeal and/or laryngeal and/or glottic and/or supraglottic and/or subglottic pressure, sound including presence and/or absence and/or amplitude and/or volume and/or pitch and/or frequency and/or sound quality and/or timbre of snoring and/or sturtor and/or stridor and/or any airway noise, longitudinal compression wave data including snoring and/or sturtor and/or stridor and/or any airway noise, positional data including movement in space and/or acceleration and/or orientation, heart rate and/or rhythm and/or regularity and/or irregularity and/or pattern and/or variability, blood pressure including systolic and/or diastolic and/or mean venous and/or mean arterial blood pressure, salivary production and/or function and/or physical composition (including presence and/or function of enzymes and/or proteins and/or peptides and/or electrolytes and/or ions and/or antibodies and/or peptides and/or hormones and/or metabolites and/or microbes and/or toxins and/or drugs and or genetic material and/or lipids and/or pH), and/or chemical composition (including presence and/or function of enzymes and/or proteins and/or peptides and/or electrolytes and/or ions and/or antibodies and/or peptides and/or hormones and/or metabolites and/or microbes and/or toxins and/or drugs and or genetic material and/or lipids and/or pH), and/or salivary flow, and/or salivary pH, autonomic nervous system activity including sympathetic and/or parasympathetic activity, vasoconstriction, vasodilation, mucosal color and/or volume and/or elasticity and/or tensile strength and/or compressibility and/or viscoelasticity and/or hardness and/or softness and/or thickness and/or heat capacity and/or thermal conductivity and/or optical properties and/or transparency and/or light scattering and/or light absorption and/or cellular integrity and/or cellular content and/or permeability and/or absorption and/or gene expression and/or protein expression and/or motility and/or oxygen consumption and/or nutrient utilization and/or receptor expression, vascularization, nerve activity and/or function, muscle activity and/or function, electromyography, electrocardiography, electrooculography, electroencephalography, endothelial activity and/or function, epithelial activity and/or function, plethysmography, temperature, heat capacity, and/or any correlate to the aforementioned parameters, and/or any combination therein. The foregoing are just a few examples of a therapy delivery system and methods of monitoring and/or improving therapy of a patient’s for sleep disordered breathing, however embodiments of the invention described hereafter are not necessarily limited to the abovedescribed.

[0099] The integration of sensors into a neurostimulation oral appliance for the treatment of obstructive sleep apnea (OSA) offers the potential for significant advancements in the diagnosis, treatment, and monitoring of this condition. By embedding sensors within the appliance, real-time data can be collected on various physiological parameters, enabling personalized treatment, improved efficacy, and enhanced patient compliance. A variety of one or more sensors may be incorporated into different components of the neurostimulation oral appliance including but not limited to any of electrophysiological sensors, respiratory sensors, position and movement sensors, timing sensors, salicary sensors, breath sensors, and/or biometric sensors, among others. Examples of electrophysiological sensors include but are not limited to electromyography (EMG) sensors to measure muscle activity in the tongue, and/or palatal, and/or pharyngeal, and/or airway, and/or jaw, and/or respiratory muscles, among others; electroencephalography (EEG) sensors to monitor brain activity, particularly sleep stages and arousals; electrooculography (EOG) sensors to track eye movements, indicating sleep stages and rapid eye movement (REM) sleep; and ohmmeters to track tissue impedance, indicating tissue wetness, electrode contact quality, and resistance to stimulation, among others. Examples of respiratory sensors include but are not limited to thermistor-based airflow sensors to measure change in temperature caused by airflow, and/or piezoelectric airflow sensors to measure airflow directly and convert it into electrical signals, and/or gauge piezoresistive pressure sensors to measure air pressure or pressure differentials in the airway, and/or capacitive pressure sensor to measure air pressure or pressure differentials in the airway, and/or hot-wire anemometers to measure airflow velocity by heating a wire and measuring the cooling effects of airflow, and/or microphones to measure and record snoring and/or sturtor and/or stridor and/or airway noise in order to measure sound response during respiration, and/or thoracic and abdominal impedance sensors to measure changes in electrical impedance across the chest and abdomen during respiration, among others. These respiratory sensors may be used to determine physiological parameters including but not limited to volume and velocity of air moving through the upper airway, respiratory rate, tidal volume, respiratory rhythm, and apnea/hypopnea events, among others. Examples of position and movement sensors include but are not limited to accelerometers to measure acceleration in three axes and monitor jaw movements, head position, and appliance movement; gyroscopes to measure angular velocity and orientation to detect head movements and changes in sleep position; magnetometers to measure magnetic field strength and determine the orientation of the appliance and head in relation to the magnetic field; and strain gauges to measure strain or deformation in the appliance and monitor jaw movements and appliance flexure, among others. Examples of timing sensors include but are not limited to real-time clocks to provide accurate time keeping to measure sleep onset and duration and align other sensor data with sleep stages; event counters to count occurrences of specific events including but not limited to apneas, hypopneas, bruxism events, arousals, appliance shifting, and appliance removal, among others; interval timers to measure time intervals between events to calculate latency between entering prone position and onset of sleep, latency between stimulation and muscular and/or airflow response, length of sleep cycle phases, and duration of apnea, hypopnea, and/or bruxism events, among others; and timestamping circuits to assign precise timestamps to data points to enable correlation of data from different sensors, among others. Examples of salivary sensors include pH sensors, electrolyte sensors, and biomarker sensors to detect changes in salivary chemistry in response to apnea and/or neuromodulation. Examples of breath sensors include oxygen sensors, carbon dioxide sensors, and/or other volatile content sensors to detect changes in breath composition as a response to apnea events and/or neuromodulation. Examples of biometric sensors include heart rate sensors in order to measure heart rate and heart rate variability in order to assess cardiovascular response to sleep apnea, evaluate overall sleep quality, detect arrhythmias, and/or asses cardiovascular response to neurostimulation; blood oxygen sensors (oximeters) including infrared light-emitting diode and photoplethysmography sensors to measure blood oxygen saturation levels in order to assess the severity of oxygen saturation during apnea and/or hypopnea events, to detect and measure the frequency of apnea and/or hypopnea events, and to assess the effectiveness of neurostimulation on improving oxygen saturation, among others; blood pressure sensors to measure blood pressure including systolic and/or diastolic pressure and/or mean arterial or venous pressure and/or pressure waveform in order to assess physiological response to apnea and/or neuromodulation; temperature sensors including thermistors, resistance temperature detectors, thermocouples, semiconductor-based (IC) temperature sensors, and/or infrared thermometers, among others in order to measure patient body temperature and monitor core temperature changes related to sleep stages and apnea response; and galvanic skin response sensors to measure changes in skin conductance in order to assess stress levels and arousal patterns during sleep, among others. Sensors may be located fully encapsulated within the oral appliance; located according to positioning of specific anatomy within the oral cavity including but not limited to gum capillary vessels, airway muscles, the hard palate, the soft palate, the maxilla, the mandible, motor nerves, sympathetic nerves, parasympathetic nerves, sensory nerves, dentition, and/or brain matter, among others; and/or located according to positioning of specific anatomy outside of the oral cavity including but not limited to fingers, palms, wrists, the forehead, armpits, the rectal cavity, the neck, the chest, the mouth, the nasal cavity, earlobes, the jaw, the chin, the eyes, the scalp, and/or the head, among others. Embedded sensors allow for closed-loop feedback and control over stimulation parameters including stimulation onset delay, stimulation onset trigger, stimulation current amplitude, stimulation voltage amplitude, stimulation frequency, stimulation duty cycle, stimulation pulse width, and/or waveform shape, among others. Further, real-time data may be used to signal to the pulse generator to initiate delivery of the neuromodulation after sleep onset or in a specific phase of sleep according to the patient’s needs. This may be programmed by any healthcare practitioner or technician or person initiating and programming therapy in order to optimize therapeutic efficacy and prevent arousal from the neuromodulation therapy before or during sleep. The foregoing are just a few examples of a therapy delivery system and methods of monitoring and/or improving therapy of a patient’s sleep disordered breathing, however embodiments of the invention described hereafter are not necessarily limited to the above-described.

[0100] In an embodiment, focused neuromodulation signals may be delivered differentially to varying submucosal depths in order to modulate a nerve and/or nerves and/or a muscle and/or muscles at varying distances from the mucosal surface. This allows for precise control over the spatial and temporal parameters of neuromodulation to enable more targeted and effective therapeutic intervention. Varying depths of penetration may be achieved by modulation of pulse width, and/or current amplitude, and/or current density, and/or voltage amplitude, and/or frequency, and/or duty cycle, and/or constructive interference with intersecting waveforms and/or destructive interference with intersecting waveforms and/or physical amplification of waveforms and/or physical impedance of waveforms and/or any combination therein. Varying depths of neuromodulation may also be achieved by electrode design, and/or shape, and/or size, and/or position, and/or material, and/or differential impedance, and/or quality of contact with tissue, and/or density of array, and/or fabrication method, and/or polarity, and/or any other component of electrode design and/or any combination therein. For example, microneedle arrays may be utilized to achieve varying depth and breadth of neuromodulation, microelectrode arrays may be utilized to achieve varying depth and breadth of neuromodulation, concentric coil electrodes may be utilized to achieve varying depth and breadth of neuromodulation, concentric ring electrodes may be utilized to achieve varying depth and breadth of neuromodulation, multi-layer electrodes may be utilized to achieve varying depth and breadth of neuromodulation, flexible electrodes may be utilized to achieve varying depth and breadth of neuromodulation, penetrating electrodes may be utilized to achieve varying depth and breadth of neuromodulation, electrode arrays may be utilized to achieve varying depth and breadth of neuromodulation, monopolar electrodes may be utilized to achieve varying depth and breadth of neuromodulation, bipolar electrodes may be utilized to achieve varying depth and breadth of neuromodulation, multipolar electrodes may be utilized to achieve varying depth and breadth of neuromodulation, and/or any combination of electrode design therein may be utilized to achieve varying depth and breadth of neuromodulation. Novel electrode materials and configurations allow for precise control over the spatial and temporal parameters of neural stimulation. By carefully selecting electrode materials with distinct electrical properties and manipulating surface characteristics, it is possible to achieve varying degrees of tissue penetration and current spread, thereby enabling the modulation of neural activity at specific depths and within defined regions of the nervous system. Surface characteristics of the electrode play a crucial role in determining the interface with the neural tissue. For instance, electrode surfaces with hydrophilic properties can enhance tissue integration, biocompatibility and reduce inflammation, potentially improving stimulation efficacy and reducing adverse effects. Conversely, hydrophobic surfaces may minimize tissue adhesion and facilitate electrode removal. The roughness of the electrode surface can also influence neural cell behavior. A textured surface may promote cell attachment and growth, while a smooth surface may reduce tissue damage. Additionally, the presence of specific biofunctional molecules on the electrode surface can be utilized to target specific cell types or induce desired biological responses. The selection of electrode material is critical for achieving desired neuromodulation effects. For example, traditional metallic materials, and/or metallic alloys, and/or metal oxides, and/or conductive polymers, and/or carbon-based conductive materials, and/or conductive ceramics, and/or conductive hydrogels, and/or conductive silicon materials and/or any combination therein including combinations of materials within one category may be used for electrode material. Examples of traditional metallic materials that may be used include but are not limited to any of platinum, gold, titanium, silver, copper, nickel, zinc and tungsten, and palladium, among others. Examples of metallic alloys that may be used include but are not limited to any of stainless steel, nickel-chromium, platinum-iridium, and silver-silver chloride, among others. Examples of metal oxides include but are not limited to any of tin oxide, indium tin oxide, ruthenium oxide, and titanium oxide, among others. Examples of conductive polymers that may be used include but are not limited to any of polyaniline, polypyrrole, PEDOT (poly(3,4-ethylenedioxythiophene), and polythiophene, among others. Examples of carbon-based conductive material include but are not limited to any of carbon fiber, graphene, diamondlike carbon, graphite, carbon nanotubes, and carbon black, among others. Examples of conductive ceramics include but are not limited to any of lanthanum strontium manganite, lead oxide, ruthenium dioxide, bismuth ruthenate, bismuth iridate, indium tin oxide, lanthanum-doped strontium titanate, and ferrites, among others. Examples of conductive hydrogels include but are not limited to any of polpyrrole hydrogels, polyaniline hydrogels, PEDOT:PSS (poly(3,4-ethylenedioxythiophene:polystyrene sulfonate) hydrogels, carbon nanotube hydrogels, graphene hydrogels, silver nanoparticle hydrogels, gold nanoparticle hydrogels, ionic hydrogels, and hybrid hydrogels, among others. Examples of conductive silicone materials that may be used include but are not limited to N-type silicon, P-type silicon, silicon carbide, silicon nitride, and silicon-based conductive polymers, among others.

[0101] Without wishing to be bound by a particular embodiment, a method and system for treating sleep disordered breathing, may be designed, manufactured, built, constructed, formed, assembled, shaped, molded, fabricated or produced such that electrodes are placed according to specific patient anatomy in order to achieve airway opening and optimal improvement in a patient’s sleep disordered breathing. The method of placing these electrodes within the final device assembly may include direct embedding, surface mounting, masked thermoforming, flexible circuitry, 3D-printing, electrodeposition, laser-induced forward transfer, inkjet printing, and electrode encapsulation, among others. Direct embedding involves directly incorporating electrodes into the appliance material during the manufacturing process to enable a streamlined design and precise electrode placement. Surface mounting involves attaching electrodes to the surface of the pre-fabricated appliance using adhesives, clips, or other mechanical fasteners to allow for flexibility in electrode placement. Masked thermoforming involves thermoforming the mechanical portions of the appliance around the dental mold while masking the electrodes, enabling them to become exposed while keeping the remainder of the circuitry fully embedded and sealed. Flexible circuits involve containing embedded electrodes in the overall flexible circuitry integrated into the appliance in order to enable intricate electrode configurations and potential integration of additional components such as sensors or wireless communication components. 3D-printing technologies involve utilizing additive manufacturing to allow for the creation of complex structures with electrodes directly embedded within the printed material to enable exceptional design freedom and customization. Electrodeposition involves direct depositing of electrodes onto the appliance surface or into pre -formed molds using electrochemical processes to offer precise control over electrode geometry and material composition. Laser-induced forward transfer involves transferring electrode materials onto the appliance surface using laser energy to allow for the deposition of various materials and precise pattern formation. Inkjet printing involves deposition of conductive inks containing electrode materials onto the appliance surface in desired patterns to enable flexibility in electrode design integration with other manufacturing processes. Hybrid embedding techniques exist utilizing one or more of the techniques stated previously. For example, combination of direct embedding and surface mounting could involve embedding a base electrode structure within the appliance material and then attaching additional electrodes or components to the surface to offer a balance between integration and flexibility. Another example may include combining flexible circuits with 3D printed structures to create complex and customized electrode configurations. The flexible circuit can be integrated into the 3D printed base for improved conductivity and reliability. Additionally, electrodes may require protection from the oral environment which may be provided by materials selection, encapsulation, and/or coating, among other methods.

[0102] Without wishing to be bound by a particular embodiment, a method and system for treating sleep disordered breathing, may be designed, manufactured, built, constructed, formed, assembled, shaped, molded, fabricated or produced such that sensors are placed according to specific patient anatomy in order to measure a variety of physiological, environmental, and/or biometric data, among others. The method of placing these sensors within the final device assembly may include direct embedding, surface mounting, masked thermoforming, flexible circuitry, 3D-printing, and/or sensor encapsulation, among others. Direct embedding involves directly incorporating sensors into the appliance material during the manufacturing process to enable a streamlined design and precise sensor placement. Surface mounting involves attaching sensors to the surface of the pre-fabricated appliance using adhesives, clips, or other mechanical fasteners to allow for flexibility in sensor placement. Masked thermoforming involves thermoforming the mechanical portions of the appliance around the dental mold while masking the sensors, enabling them to become exposed while keeping the remainder of the circuitry fully embedded and sealed. Flexible circuits involve containing embedded sensors in the overall flexible circuitry integrated into the appliance in order to enable intricate sensor configurations and potential integration of additional components such as sensors or wireless communication components. 3D-printing technologies involve utilizing additive manufacturing to allow for the creation of complex structures with sensors directly embedded within the printed material to enable exceptional design freedom and customization. Hybrid embedding techniques exist utilizing one or more of the techniques stated previously. For example, combination of direct embedding and surface mounting could involve embedding a base sensor structure within the appliance material and then attaching additional sensors or components to the surface to offer a balance between integration and flexibility. Another example may include combining flexible circuits with 3D printed structures to create complex and customized sensor configurations. The flexible circuit can be integrated into the 3D printed base for improved conductivity and reliability. Additionally, sensors may require protection from the oral environment which may be provided by materials selection, encapsulation, and/or coating, among other methods.

[0103] Without wishing to be bound by a particular embodiment, a method and system for treating sleep disordered breathing, may be designed, manufactured, built, constructed, formed, assembled, shaped, molded, fabricated or produced such that circuitry components including but not limited to microcontrollers, power management ICs, wireless communication modules, sensor interface circuitry, stimulator driver circuitry, and/or batters are placed and encapsulated within the system to enable conformation of the system to patient anatomy. The method of placing this circuitry within the final device assembly may include direct embedding, surface mounting, masked thermoforming, flexible circuitry, 3D-printing, thin-film electronics, and/or circuit encapsulation, among others. Direct embedding involves directly incorporating circuitry into the appliance material during the manufacturing process to enable a streamlined design and precise sensor placement. This may include thermoforming over the circuitry to seal it within the appliance or initial attachment before sealing of the circuitry components. Surface mounting involves attaching sensors to the surface of the pre-fabricated appliance using adhesives, clips, or other mechanical fasteners to allow for flexibility in circuit placement. Circuit components may be circuit mounted before sealing, coating, or other forms of encapsulation. Masked thermoforming involves thermoforming the mechanical portions of the appliance around the dental mold while masking the circuitry, enabling them to be protected from the thermoforming temperatures and materials during the assembly process. Flexible circuits involve utilizing flexible printed circuit boards that can be integrated into the appliance's structure, allowing for complex circuit layouts and adaptability to the oral environment in order to enable intricate sensors configurations and potential integration of additional components such as sensors or wireless communication components. 3D-printing technologies involve utilizing additive manufacturing to allow for the creation of complex structures with circuitry directly embedded within the printed material to enable exceptional design freedom and customization. Thin-film electronics involve depositing electronic components directly onto the appliance material, offering miniaturization and integration benefits. Hybrid embedding techniques exist utilizing one or more of the techniques stated previously. For example, combination of direct embedding and surface mounting could involve embedding a base circuit structure within the appliance material and then attaching additional circuitry components to the surface to offer a balance between integration and flexibility. Another example may include combining flexible circuits with 3D printed structures to create complex and customized circuitry configurations. The flexible circuit can be integrated into the 3D printed base for improved conductivity and reliability. Additionally, circuitry may require protection from the oral environment which may be provided by materials selection, encapsulation, and/or coating, among other methods.

[0104] In an embodiment, energy may be delivered with varying parameters from a delivery system according to the disease state desired to be treated. In an embodiment, the energy signal may be an electrical or magnetic or ultrasound or piezoelectric or radiation or electromagnetic or radiofrequency or mechanical or chemical or optical or light or thermal or sound signal or any other signal, and/or any combination therein. In an embodiment, the signal delivered may be delivered continuously and/or in single and/or successive pulse trains. Such continuous signals and pulse trains may be in the form of square waves, sine waves, triangle waves , exponential waves, sawtooth waves, pulse waves, arbitrary waveforms, and/or any combination therein. In an embodiment, the energy delivered may be delivered to achieve electroporation and/or photodynamic therapy in assisting intracellular and/or intratumoral and/or extratumoral, and/or peritumoral, and/or topical, and/or systemic treatment of a disease such as a tumor, and/or any combination therein. In an embodiment energy may be delivered at OV/cm to lOOOkV/cm in order to induce electroporation in a benign tumor, and/or malignant tumor, and/or precancerous tumor or lesion, and/or cancer, and/or carcinoma, and/or sarcoma, and/or any lesion, and/or any tissue, and/or any combination therein. These parameters are exemplary only, and may be adjusted above or below the ranges given to achieve suitable results. In an embodiment, the electroporation may be intended to increase distribution, and/or dispersion, and/or intracellular, and/or intratumoral, and/or extratumoral, and/or peritumoral, and/or topical, and/or systemic concentration of a molecule, and/or drug, and/or nanoparticle, and/or biologic, and/or gene, and/or ion, and/or any antitumor therapy in a tumor, and/or any combination therein. In an embodiment, the electroporation signal delivered may be delivered continuously and/or in successive pulse trains. Such continuous signals and pulse trains may be in the form of square waves, sine waves, triangle waves , exponential waves, sawtooth waves, pulse waves, arbitrary waveforms, and/or any combination therein. Such pulse trains may be in the waveform of monophasic or biphasic, symmetric or asymmetrical, and/or any combination therein. Pulse trains may be delivered in repeated bursts in the range of 1 pulse per train to 1,000,000 pulses per train. Pulse trains may be delivered in intervals of 0.01 microseconds with a range of 0.01 microseconds to 600 seconds. Each burst may be delivered in a plurality of parameters including current amplitudes, voltage amplitudes, frequencies, pulse widths, duty cycles, pulse configurations and/or any combination therein. Such current amplitudes may be delivered in the range of 0.01mA to 1A, these parameters are exemplary only, and may be adjusted above or below the ranges given to achieve suitable results. Such frequencies may be delivered in the range of 0.01Hz to 10,000GHz, these parameters are exemplary only, and may be adjusted above or below the ranges given to achieve suitable results. Such pulse widths may be delivered in the range of 0.01 Ds to 600s , these parameters are exemplary only, and may be adjusted above or below the ranges given to achieve suitable results. Such duty cycles may be delivered in the range of 0% to 100% , these parameters are exemplary only, and may be adjusted above or below the ranges given to achieve suitable results. Such pulse configurations may be delivered in any configuration to achieve suitable results, including voltage amplitude ramp-up, current amplitude ramp up, voltage amplitude stepdown, current amplitude step-down, variable pulse widths, variable duty cycles, variable current amplitudes, variable voltage amplitudes, sine-wave configurations, square-wave configurations, triangle wave configuration , exponential wave configurations, sawtooth wave configurations, pulse wave configurations, arbitrary wave configurations, in temporal patterns, in temporal sequences, in random paterns, in random sequences, and/or any combination therein. Such amplitude ramps can be configured in intervals of 0.01 microseconds in the range of 0.0 to 600 seconds, these parameters are exemplary only, and may be adjusted above or below the ranges given to achieve suitable results. In an embodiment, neuromodulation may be delivered with varying modulation parameters according to the disease being treated or monitored within or above or below the aforementioned ranges. In an embodiment the electroporation may be reversible, and/or irreversible and/or thermal irreversible, and/or any combination therein. In an embodiment the electroporation may be intended to increase radiosensitivity, and/or chemosensitivity, and/or cause cell death by any mechanism of cell death of any tissue and/or tumor intended to be treated. In an embodiment the electroporation may be intended to reduce tumor volume, and/or induce tumor death, and/or facilitate radiotherapy, and/or brachytherapy, and/or chemotherapy, and/or surgery, and/or ablation, and or any therapy intended to treat a tumour, in order to improve treatment outcomes of any anti -tumor therapy or therapeutic modality or therapeutic approach, and/or any combination therein. In an embodiment, the electroporation may be intended to be delivered to a head and neck tumor in an aerodigestive tract, and/or an oral cavity, and/or an oropharynx, and/or a tonsil, and/or a hypopharynx, and/or larynx, and/or a supraglotis, and/or an epiglotis, and/or a glotis, and/or a subglotis, and/or a base of tongue, and/or a tongue, and/or a lip, and/or a nasal cavity, and/or a nasopharynx, and/or a sinus, and/or a base of skull, and/or a bone, and/or soft tissue, and/or mucosa, and/or muscle, and/or a tooth, and/or a cartilage, and/or a tendon, and/or a ligament, and/or a connective tissue, and/or a salivary gland, and/or an esophagus, and/or a lymph node, and/or a neck, and/or skin, and/or a nerve, and/or a vessel, and/or an airway, and/or any anatomical area of the head and neck, and/or any combination therein. In an embodiment, the electroporation may be intended to treat a squamous cell carcinoma, and/or a human-papilloma virus positive squamous cell carcinoma, and/or a human-papilloma virus negative squamous cell carcinoma, and/or a p-16 positive squamous cell carcinoma, and/or a p-16 negative squamous cell carcinoma, and/or a nasopharyngeal carcinoma, and/or a pleiomorphic adenoma, and/or a Warthin’s tumor, and/or a mucoepidermoid carcinoma, and/or an acinic cell carcinoma, and/or an adenoid cystic carcinoma, and/or a salivary duct carcinoma, and/or a thyroid adenoma, and/or a papillary thyroid carcinoma, and/or a follicular thyroid carcinoma, and/or a medullary thyroid carcinoma, and/or an anaplastic thyroid carcinoma, and/or a parathyroid adenoma, and/or a parathyroid carcinoma, and/or a sinonasal squamous cell carcinoma, and/or a sinonasal adenocarcinoma, and/or a sinonasal undifferentiated carcinoma, and/or a lipoma, and/or a hemangioma, and/or a sarcoma, and/or a rhabdomyosarcoma, and/or a fibrosarcoma, and/or an angiosarcoma, and/or an osteosarcoma, and/or a chondrosarcoma, and/or a liposarcoma, and/or a leiomyosarcoma, and/or a synovial sarcoma, and/or an angiosarcoma, and/or a neuroma, and/or a malignant peripheral nerve sheath tumor, and/or an epithelioid sarcoma, and/or a dermatofibrosarcoma, and/or a clear cell sarcoma, and/or an alveolar soft part sarcoma, and/or a desmoid tumor, and/or a myxofibrosarcoma, and/or an undifferentiated pleiomorphic sarcoma, and/or a gastrointestinal stromal tumor, and/or a Kaposi sarcoma, and/or a giant cell tumor of bone, and/or an adamantinoma, and/or a chordoma, and/or an Ewing sarcoma, and/or a papilloma, and/or an osteoma, and/or a chondroma, and/or a Schwannoma, and/or a neurofibroma, and/or a basal cell carcinoma, and/or a nasal tumor, and/or a nasal polyp, and/or an olfactory neuroblastoma, and/or an acoustic neuroma, and/or a melanoma, and/or a verrucous carcinoma, and/or any tumor, and/or any cancer, and/or any carcinoma, and or any combination therein. The foregoing are just a few examples of a therapy delivery system for sleep disordered breathing, however embodiments of the invention described hereafter are not necessarily limited to the above-described.

[0105] In an embodiment the electroporation energy may be delivered as and/or in combination with and/or incorporated into a retainer, and/or a non-retainer form, and/or a stent form, and/or a catheter form, and/or a cannula form, and/or a non-implant form, and/or an implant form, and/or a surgery including a nasal surgery and/or a nasopharyngeal surgery, and/or an oral cavity surgery and/or an oropharyngeal surgery and/or a palate surgery and/or a tonsil surgery and/or a lateral pharyngeal wall surgery and/or a pharyngeal surgery and/or an oropharyngeal surgery and/or a hypopharyngeal surgery and/or a tongue surgery and/or a tongue base surgery and/or a supraglottic surgery and/or an epiglottic surgery and/or a glottic surgery and/or a subglottic surgery and/or a craniofacial surgery and/or a facial bone surgery and/or a hyoid bone surgery and/or a dental surgery and/or a neck surgery and/or a thyroid surgery and/or a parathyroid surgery and/or a salivary gland surgery and/or a lymph node surgery and/or a soft tissue surgery and/or a skin surgery and/or a base of skull surgery and/or a sinus surgery and/or an orbital surgery and/or an eye surgery and/or a vascular surgery and/or a nerve surgery and/or a minimally- invasive procedure and/or non-invasive procedure, an orthodontic therapy and/or device and/or drug and/or procedure and/or surgery, a dental therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery, an endodontic therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery, a sleep disorder therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery, a mouth guard device and/or appliance and/or retainer and/or prothesis, a bruxism therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery, a nasal therapy and/or device and or prosthesis and/or drug, and/or a nasopharyngeal therapy and/or device and/or prosthesis and/or drug, a nasal airway therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery, and/or an oral cavity therapy and/or device and/or prosthesis and/or retainer and/or drug, an oropharyngeal therapy and/or device and/or prosthesis and/or drug, and/or a palate therapy and/or device and/or prosthesis and/or drug, a tonsil therapy and/or device and/or prosthesis and/or drug, a lateral pharyngeal wall therapy and/or device and/or prosthesis and/or drug, a hypopharyngeal therapy and/or device and or prosthesis and/or drug, a tongue therapy and/or device and/or prosthesis and/or drug, a tongue base therapy and/or device and/or prosthesis and/or drug, a supraglottic therapy and/or device and/or prosthesis and/or drug, an epiglottic therapy and/or device and/or prosthesis and/or drug, and/or a glottic therapy and/or device and/or prosthesis and/or drug, a subglottic therapy and/or device and/or prosthesis and/or drug, a craniofacial therapy and/or device and/or prosthesis and/or drug, a facial bone therapy and/or device and or prosthesis and/or drug, and/or a dental therapy and/or device and/or retainer and/or prosthesis and/or drug, a neck therapy and/or device and/or retainer and/or prosthesis and/or drug, and/or a non-invasive therapy and/or device and/or prosthesis and/or drug, a neuromodulation therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system, a nerve therapy and/or device and/or drug and/or procedure and/or surgery and/or method and/or system, and/or a thyroid therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery, and/or a parathyroid therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery, and/or a salivary gland therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery, and/or a lymph node therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery, and/or a soft tissue therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery, and/or a connective tissue therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery, and/or a mucosal therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery , and/or a skin therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery, and/or a base of skull therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery, and/or a sinus therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery, and/or an orbital therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery, and/or an eye therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery, and/or a vascular therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery, and/or a nerve therapy and/or device and/or retainer and/or prosthesis and/or drug and/or procedure and/or surgery, and/or any therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system that is intended to treat a tumor, and/or any combination therein. The foregoing are just a few examples of a therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system for treatment of tumors, however embodiments of the invention described hereafter are not necessarily limited to the above-described therapy and/or device and/or prosthesis and/or drug and/or procedure and/or surgery and/or method and/or system, and/or any combination therein.

3 , Methods and Systems for Neuromodulation

3, A, Neuromodulation Methods

[0106] The present disclosure provides methods and systems for treating sleep disordered breathing (SDB), a condition characterized by pauses or disturbances in breathing during sleep. One prevalent form of SDB is obstructive sleep apnea (OSA), which is characterized by repeated airway obstruction during sleep, leading to airflow limitation or cessation. This condition can lead to various health risks, including hypertension, cerebrovascular events, cardiovascular events, and metabolic disorders such as diabetes. Current treatment options, such as continuous positive airway pressure (CPAP) therapy and surgical interventions, may not be effective for all patients, and adherence to these treatments can be challenging. [0107] The disclosed methods and systems address these challenges by delivering a neuromodulation signal to specific nerves or muscles associated with the palatal and pharyngeal regions. The neuromodulation signal can activate these nerves or muscles, thereby increasing their tone and reducing or preventing airway obstruction. This approach may offer a novel and effective treatment for patients with OSA, particularly those with complete concentric collapse of the palate (CCCp), a phenotype associated with greater disease severity and a higher propensity to CPAP failure.

[0108] The neuromodulation signal can be delivered using various forms of energy, including electrical, magnetic, ultrasound, piezoelectric, radiation, electromagnetic, radiofrequency, mechanical, chemical, optical, or sound energy, or any combination thereof. The signal can be delivered continuously or in successive pulse trains, and the modulation parameters can be adjusted to optimize the treatment outcome for each patient. The disclosed methods and systems may be incorporated into various forms of devices, including oral appliances, implantable devices, and wearable devices, providing flexibility and convenience for the patient.

[0109] In some embodiments, the disclosed methods and systems may also be used to treat other conditions that may benefit from neuromodulation, including central sleep apnea, sleep disorders, hypertension, hypotension, autonomic dysfunction, heart rate regulation, blood pressure regulation, and various other conditions. Thus, the disclosed methods and systems may provide a versatile and effective approach for treating a wide range of conditions associated with neuromuscular control and function. [0110] Referring to FIG. 1, a flowchart illustrates a method 100 for treating sleep disordered breathing. The method 100 begins with block 102, which involves delivering a neuromodulation signal to a target site. The target site may be proximate to a nerve or muscle associated with the palatal and/or pharyngeal musculature. The nerve may be one or a combination of the lesser palatine nerve, the nerve to tensor veli palatini, or branches of the pharyngeal plexus that innervate the levator veli palatini, palatopharyngeus, palatoglossus, middle constrictor, and/or superior constrictor. The muscle may be one or a combination of the levator veli palatini muscle, musculus uvulae muscle, palatopharyngeus muscle, palatoglossus muscle, tensor veli palatini muscle, middle constrictor muscle, and/or superior constrictor muscle.

[0111] The neuromodulation signal may be delivered by at least one electrode placed in electrical communication with the target site. The electrode may be activated to deliver an electrical signal to the target site, as represented by block 104. The electrical signal may stimulate the motor neurons of the targeted nerves or the muscle fibers of the targeted muscles, thereby activating the palatal and pharyngeal musculature. The activation of these muscles may increase their tone, reducing or preventing airway obstruction during sleep.

[0112] The method 100 concludes with block 106, which involves improving the patient's sleep disordered breathing via the delivery of the neuromodulation signal. The improvement in sleep disordered breathing may be manifested as a reduction in the frequency and severity of apnea or hypopnea events, an increase in the quality of sleep, a decrease in daytime sleepiness, and/or other improvements in the patient's condition. The method 100 thus provides a novel and effective approach for treating sleep disordered breathing, particularly in patients with obstructive sleep apnea and other forms of sleep disordered breathing.

[0113] Referring to FIG. 2, a flowchart illustrates a method 200 for treating sleep disordered breathing. The method 200 begins with block 202, which involves delivering a neuromodulation signal to a target site. The target site may be proximate to a specific palatal muscle and/or a pharyngeal muscle. The specific muscles may include one or combinations of the levator veli palatini muscle, musculus uvulae muscle, palatopharyngeus muscle, palatoglossus muscle, tensor veli palatini muscle, middle constrictor muscle, and/or superior constrictor muscle.

[0114] The neuromodulation signal may be delivered by at least one electrode placed in electrical communication with the target site. The electrode may be activated to deliver an electrical signal to the target site, as represented by block 204. The electrical signal may stimulate the muscle fibers of the targeted muscles, thereby activating the palatal and pharyngeal musculature. The activation of these muscles may increase their tone, reducing or preventing airway obstruction during sleep.

[0115] The method 200 concludes with block 206, which involves improving the patient's sleep disordered breathing via the delivery of the neuromodulation signal. The improvement in sleep disordered breathing may be manifested as a reduction in the frequency and severity of apnea or hypopnea events, an increase in the quality of sleep, a decrease in daytime sleepiness, and/or other improvements in the patient's condition. The method 200 thus provides a novel and potentially effective approach for treating sleep disordered breathing, particularly in patients with obstructive sleep apnea and other forms of sleep disordered breathing.

[0116] Referring to FIG. 3, a flowchart illustrates a method 300 for treating sleep disordered breathing through a two-stage neuromodulation process. The method 300 begins with block 302, which involves delivering a neuromodulation signal to a target site proximate to one or combinations of nerves that innervate the palatal and/or pharyngeal musculature. The nerves may include the lesser palatine nerve, the nerve to tensor veli palatini, and branches of the pharyngeal plexus that innervate the levator veli palatini, palatopharyngeus, palatoglossus, middle constrictor, and/or superior constrictor.

[0117] Upon delivery of the neuromodulation signal, the palatal and pharyngeal musculature is activated, as represented by block 304. This activation may increase the tone of these muscles, reducing or preventing airway obstruction during sleep.

[0118] The method 300 then proceeds to block 306, which involves delivering a neuromodulation signal to a target site proximate to one or combinations of specific palatal and pharyngeal muscles. These muscles may include the levator veli palatini muscle, musculus uvulae muscle, palatopharyngeus muscle, palatoglossus muscle, tensor veli palatini muscle, middle constrictor muscle, and/or superior constrictor muscle.

[0119] Following the delivery of the neuromodulation signal, the palatal and pharyngeal musculature is again activated, as represented by block 308. This second stage of muscle activation may further increase the tone of these muscles, enhancing the reduction or prevention of airway obstruction.

[0120] The method 300 concludes with block 310, which involves improving the patient's sleep disordered breathing via the delivery of the neuromodulation signal. The improvement in sleep disordered breathing may be manifested as a reduction in the frequency and severity of apnea or hypopnea events, an increase in the quality of sleep, a decrease in daytime sleepiness, and/or other improvements in the patient's condition. The method 300 thus provides a novel and potentially effective approach for treating sleep disordered breathing, particularly in patients with obstructive sleep apnea and other forms of sleep disordered breathing.

[0121] Referring to FIG. 4, an anatomical view of the palatal and pharyngeal musculature and associated nerves is illustrated. The illustration label 400 shows various muscles and nerves involved in the upper airway. The hard palate 410 is depicted at the top of the image. The tensor veli palatini (TVP) muscle 412 and levator veli palatini (LVP) muscle 414 are shown extending from the hard palate region.

[0122] The nerve to tensor veli palatini (N to TVP) 416 branches from the mandibular division of the trigeminal nerve (V3) 418. The lesser palatine nerve (LPN) 408 is shown innervating the palatal region. The musculus uvulae (MU) 434 is depicted in the central area. The palatopharyngeus (PP) muscle 436 and palatoglossus (PG) muscle 406 are shown extending downward.

[0123] The superior constrictor (SC) muscle 432 and middle constrictor (MC) muscle 430 are illustrated in the pharyngeal region. Branches to these muscles are shown, including the branch to SC 422 and branch to MC 428. The pharyngeal plexus is represented by PhPlex-X left 404, PhPlex-IX left 402, PhPlex-X right 424, and PhPlex-IX right 426. These innervate various structures in the pharyngeal region. Additional nerve branches are depicted, including the branch to LVP 420, which innervates the levator veli palatini muscle.

[0124] In some aspects, a method for treating sleep disordered breathing may involve placing at least one electrode into electrical communication with a target site of a palatal muscle, a pharyngeal muscle, and/or a nerve that innervates the palatal muscle and/or the pharyngeal muscle. The target site may be selected to target one or combinations of: a tensor veli palatini muscle, a levator veli palatini muscle, a palatopharyngeus muscle, a palatoglossus muscle, a musculus uvulae muscle, a superior constrictor muscle, and/or a middle constrictor muscle.

[0125] In some cases, the target site may be selected to target one or combinations of: a branch of a maxillary division of a trigeminal nerve that innervates a levator veli palatini muscle including a lesser palatine nerve; a palatopharyngeus muscle including the lesser palatine nerve; a palatoglossus muscle including the lesser palatine nerve; a musculus uvulae muscle including the lesser palatine nerve; a branch of a mandibular division of the trigeminal nerve that innervates a tensor veli palatini muscle including a nerve to tensor veli palatini; a branch of a pharyngeal plexus that innervates a superior constrictor muscle including a pharyngeal plexus branch to the superior constrictor muscle; and/or a nerve to the superior constrictor muscle.

[0126] In some embodiments, activating the at least one electrode to deliver the electrical signal to the target site includes stimulating motor neurons of one or combinations of: a maxillary branch of a trigeminal nerve that innervates a levator veli palatini muscle, a palatoglossus muscle, a palatopharyngeus muscle, a musculus uvulae muscle including motor neurons of a lesser palatine nerve, a mandibular branch of the trigeminal nerve that innervates a tensor veli palatini muscle including motor neurons of a nerve to tensor veli palatini, a branch of a pharyngeal plexus that innervates a superior constrictor muscle including motor neurons of a nerve to superior constrictor muscle. [0127] In some cases, the target site is one of a plurality of target sites of nerves or muscles that are in communication with one or more palatal muscles and/or pharyngeal muscles. The plurality of target sites may be selected to target a set including one or combinations of: a tensor veli palatini muscle, a levator veli palatini muscle, a palatopharyngeus muscle, a palatoglossus muscle, a musculus uvulae muscle, a superior constrictor muscle, and/or a middle constrictor muscle.

[0128] Referring to FIG. 5, an oral cavity view 500 of the palatal and pharyngeal musculature is illustrated. The figure shows both a frontal view of the open mouth and a detailed view of the soft palate structures. The palatopharyngeus muscle 502 is depicted extending vertically along the sides of the pharynx. Adjacent to it is the tonsil 504. The palatoglossus muscle 506 is shown connecting the soft palate to the tongue.

[0129] The lesser palatine foramen 508 is indicated in the hard palate region. The levator veli palatini muscle 510 and the tensor veli palatini muscle 512 are illustrated as they extend from the skull base to the soft palate. The musculus uvulae 514 is depicted at the center of the soft palate, forming the uvula. The palatine aponeurosis 516 is shown as a fibrous sheet in the soft palate, serving as an attachment point for several muscles.

[0130] In some aspects, a method for treating sleep disordered breathing may involve placing at least one electrode into electrical communication with a target site of a palatal muscle, a pharyngeal muscle, and/or a nerve that innervates the palatal muscle and/or the pharyngeal muscle. The target site may be selected to target one or combinations of: a tensor veli palatini muscle 512, a levator veli palatini muscle 510, a palatopharyngeus muscle 502, a palatoglossus muscle 506, a musculus uvulae muscle 514, a superior constrictor muscle, and/or a middle constrictor muscle.

[0131] In some cases, the electrical signal may be delivered to the target site, where the target site is selected to target one or combinations of: the tensor veli palatini muscle 512, the superior constrictor muscle, and/or a middle constrictor muscle. The electrical signal may stimulate the muscle fibers of the targeted muscles, thereby activating the palatal and pharyngeal musculature. The activation of these muscles may increase their tone, potentially reducing or preventing airway obstruction during sleep.

[0132] Referring to FIG. 6, a flowchart illustrates a method 600 for treating sleep disordered breathing by targeting the intrinsic or extrinsic muscles of the tongue. The method 600 begins with block 602, which involves delivering a neuromodulation signal to a target site proximate to one or combinations of intrinsic or extrinsic tongue muscles. The intrinsic tongue muscles may include the superior longitudinal muscle, inferior longitudinal muscle, transverse muscle, and/or vertical muscle. The extrinsic tongue muscles may include the genioglossus muscle, hyoglossus muscle, and/or styloglossus muscle.

[0133] The neuromodulation signal may be delivered by at least one electrode placed in electrical communication with the target site. The electrode may be activated to deliver an electrical signal to the target site, as represented by block 604. The electrical signal may stimulate the muscle fibers of the targeted muscles, thereby activating the intrinsic and/or extrinsic tongue musculature. The activation of these muscles may increase their tone, reducing or preventing airway obstruction during sleep. [0134] The method 600 concludes with block 606, which involves improving the patient's sleep disordered breathing via the delivery of the neuromodulation signal. The improvement in sleep disordered breathing may be manifested as a reduction in the frequency and severity of apnea or hypopnea events, an increase in the quality of sleep, a decrease in daytime sleepiness, and/or other improvements in the patient's condition. The method 600 thus provides a novel and potentially effective approach for treating sleep disordered breathing, particularly in patients with obstructive sleep apnea and other forms of sleep disordered breathing.

[0135] Referring to FIG. 7, a tongue anatomy illustration 700 is provided, showing both sagittal and frontal views of the tongue and surrounding structures. The sagittal view on the left depicts the internal muscular structure of the tongue, while the frontal view on the right shows the extrinsic muscles of the tongue.

[0136] In the sagittal view, the superior longitudinal muscle 718, inferior longitudinal muscle, transverse muscle 720, and vertical muscle 712 are shown as intrinsic muscles of the tongue, along with the mandible 710, geniohyoid 716, and genioglossus muscle 702. These muscles are responsible for altering the shape of the tongue, allowing it to change its position and shape for various functions such as speech and swallowing. In some aspects, a method for treating sleep disordered breathing may involve delivering a neuromodulation signal to a target site proximate to one or combinations of these intrinsic tongue muscles. The neuromodulation signal may stimulate the muscle fibers of these muscles, thereby activating the intrinsic tongue musculature. The activation of these muscles may increase their tone, potentially reducing or preventing airway obstruction during sleep.

[0137] The frontal view displays the dorsal tongue surface 708 and three extrinsic muscles of the tongue: the genioglossus muscle 702, the hyoglossus muscle 704, and the styloglossus muscle 706. These muscles are shown attaching to different parts of the tongue and surrounding structures, and are responsible for the gross movements of the tongue. The genioglossus muscle 702, for instance, protrudes the tongue, while the hyoglossus muscle 704 depresses and retracts it, and the styloglossus muscle 706 draws up the sides of the tongue to assist in swallowing. In some cases, a method for treating sleep disordered breathing may involve delivering a neuromodulation signal to a target site proximate to one or combinations of these extrinsic tongue muscles. The neuromodulation signal may stimulate the muscle fibers of these muscles, thereby activating the extrinsic tongue musculature. The activation of these muscles may increase their tone, potentially reducing or preventing airway obstruction during sleep.

[0138] In some embodiments, the neuromodulation signal may be delivered by at least one electrode placed in electrical communication with the target site. The electrode may be activated to deliver an electrical signal to the target site, thereby stimulating the motor neurons of the targeted nerves or the muscle fibers of the targeted muscles. The activation of these muscles may increase their tone, reducing or preventing airway obstruction during sleep. The method thus provides a novel and potentially effective approach for treating sleep disordered breathing, particularly in patients with obstructive sleep apnea and other forms of sleep disordered breathing. [0139] Referring to FIG. 8, a flowchart illustrates a method 800 for treating sleep disordered breathing. The method 800 begins with block 802, which involves delivering a neuromodulation signal to a target site proximate to one or combinations of nerves that innervate the palatal and/or pharyngeal musculature. The nerves may include the lesser palatine nerve, the nerve to tensor veli palatini, and branches of the pharyngeal plexus that innervate the levator veli palatini, palatopharyngeus, palatoglossus, middle constrictor, and/or superior constrictor.

[0140] Upon delivery of the neuromodulation signal, the palatal and pharyngeal musculature is activated, as represented by block 804. This activation may increase the tone of these muscles, reducing or preventing airway obstruction during sleep.

[0141] The method 800 then proceeds to block 806, which involves delivering a neuromodulation signal to a target site proximate to one or combinations of specific palatal and pharyngeal muscles. These muscles may include the levator veli palatini muscle, musculus uvulae muscle, palatopharyngeus muscle, palatoglossus muscle, tensor veli palatini muscle, middle constrictor muscle, and/or superior constrictor muscle.

[0142] Following the delivery of the neuromodulation signal, the palatal and pharyngeal musculature is again activated, as represented by block 808. This second stage of muscle activation may further increase the tone of these muscles, enhancing the reduction or prevention of airway obstruction.

[0143] The method 800 then proceeds to block 810, which involves delivering a neuromodulation signal to a target site proximate to a hypoglossal nerve that innervates a genioglossus muscle, and/or an ansa cervicalis nerve that innervates a strap muscle. This leads to block 812, which involves activating the genioglossus muscle and/or strap muscle.

[0144] Finally, the method 800 concludes with block 814, which involves improving the patient's sleep disordered breathing via the delivery of the neuromodulation signal. The improvement in sleep disordered breathing may be manifested as a reduction in the frequency and severity of apnea or hypopnea events, an increase in the quality of sleep, a decrease in daytime sleepiness, and/or other improvements in the patient's condition. The method 800 thus provides a novel and effective approach for treating sleep disordered breathing, particularly in patients with obstructive sleep apnea and other forms of sleep disordered breathing.

[0145] Referring to FIG. 9, a flowchart illustrates a method 900 of treating sleep disordered breathing through a multi-stage neuromodulation process. The method 900 begins with block 902, which involves delivering a neuromodulation signal to a target site proximate to one or combinations of nerves that innervate the palatal and/or pharyngeal musculature. The nerves may include the lesser palatine nerve, the nerve to tensor veli palatini, and branches of the pharyngeal plexus that innervate the levator veli palatini, palatopharyngeus, palatoglossus, middle constrictor, and/or superior constrictor.

[0146] Upon delivery of the neuromodulation signal, the palatal and pharyngeal musculature is activated, as represented by block 904. This activation may increase the tone of these muscles, potentially reducing or preventing airway obstruction during sleep. [0147] The method 900 then proceeds to block 906, which involves delivering a neuromodulation signal to a target site proximate to one or combinations of specific palatal and pharyngeal muscles. These muscles may include the levator veli palatini muscle, musculus uvulae muscle, palatopharyngeus muscle, palatoglossus muscle, tensor veli palatini muscle, middle constrictor muscle, and/or superior constrictor muscle.

[0148] Following the delivery of the neuromodulation signal, the palatal and pharyngeal musculature is again activated, as represented by block 908. This second stage of muscle activation may further increase the tone of these muscles, enhancing the reduction or prevention of airway obstruction.

[0149] The method 900 then proceeds to block 910, which involves delivering a neuromodulation signal to a target site proximate to one or combinations of intrinsic tongue muscles (such as superior longitudinal, inferior longitudinal, transverse, or vertical muscles) and/or extrinsic tongue muscles (such as genioglossus, hyoglossus, or styloglossus). This leads to block 912, which involves activating the intrinsic and/or extrinsic tongue musculature.

[0150] Finally, the method 900 concludes with block 914, which involves improving the patient's sleep disordered breathing via the delivery of the neuromodulation signal. The improvement in sleep disordered breathing may be manifested as a reduction in the frequency and severity of apnea or hypopnea events, an increase in the quality of sleep, a decrease in daytime sleepiness, and/or other improvements in the patient's condition. The method 900 thus provides a novel and effective approach for treating sleep disordered breathing, particularly in patients with obstructive sleep apnea and other forms of sleep disordered breathing.

[0151] Referring to FIG. 10, a flowchart illustrates a method 1000 of treating sleep disordered breathing through a multi-stage neuromodulation process. The method 1000 begins with block 1002, which involves delivering a neuromodulation signal to a target site proximate to one or combinations of nerves that innervate the palatal and/or pharyngeal musculature. The nerves may include the lesser palatine nerve, the nerve to tensor veli palatini, and branches of the pharyngeal plexus that innervate the levator veli palatini, palatopharyngeus, palatoglossus, middle constrictor, and/or superior constrictor.

[0152] Upon delivery of the neuromodulation signal, the palatal and pharyngeal musculature is activated, as represented by block 1004. This activation may increase the tone of these muscles, reducing or preventing airway obstruction during sleep.

[0153] The method 1000 then proceeds to block 1006, which involves delivering a neuromodulation signal to a target site proximate to one or combinations of specific palatal and pharyngeal muscles. These muscles may include the levator veli palatini muscle, musculus uvulae muscle, palatopharyngeus muscle, palatoglossus muscle, tensor veli palatini muscle, middle constrictor muscle, and/or superior constrictor muscle.

[0154] Following the delivery of the neuromodulation signal, the palatal and pharyngeal musculature is again activated, as represented by block 1008. This second stage of muscle activation may further increase the tone of these muscles, enhancing the reduction or prevention of airway obstruction. [0155] The method 1000 then proceeds to block 1010, which involves delivering a neuromodulation signal to a target site proximate to one or combinations of intrinsic tongue muscles (such as superior longitudinal, inferior longitudinal, transverse, or vertical muscles) and/or extrinsic tongue muscles (such as genioglossus, hyoglossus, or styloglossus). This leads to block 1012, which involves activating the intrinsic and/or extrinsic tongue musculature.

[0156] The method 1000 then proceeds to block 1014, which involves delivering a neuromodulation signal to a target site proximate to a hypoglossal nerve that innervates a genioglossus muscle, and/or an ansa cervicalis nerve that innervates a strap muscle. This leads to block 1016, which involves activating the genioglossus muscle and/or strap muscle.

[0157] Finally, the method 1000 concludes with block 1018, which involves improving the patient's sleep disordered breathing via the delivery of the neuromodulation signal. The improvement in sleep disordered breathing may be manifested as a reduction in the frequency and severity of apnea or hypopnea events, an increase in the quality of sleep, a decrease in daytime sleepiness, and/or other improvements in the patient's condition. The method 1000 thus provides a novel and potentially effective approach for treating sleep disordered breathing, particularly in patients with obstructive sleep apnea and other forms of sleep disordered breathing.

[0158] Referring to FIG. 11, a flowchart illustrates a method 1100 of treating sleep disordered breathing through a multi-stage neuromodulation process. The method 1100 begins with block 1102, which involves delivering a neuromodulation signal to a target site proximate to one or combinations of nerves that innervate the palatal and/or pharyngeal musculature. The nerves may include the lesser palatine nerve, the nerve to tensor veli palatini, and branches of the pharyngeal plexus that innervate the levator veli palatini, palatopharyngeus, palatoglossus, middle constrictor, and/or superior constrictor.

[0159] Upon delivery of the neuromodulation signal, the palatal and pharyngeal musculature is activated, as represented by block 1104. This activation may increase the tone of these muscles, reducing or preventing airway obstruction during sleep.

[0160] The method 1100 then proceeds to block 1106, which involves delivering a neuromodulation signal to a target site proximate to one or combinations of specific palatal and pharyngeal muscles. These muscles may include the levator veli palatini muscle, musculus uvulae muscle, palatopharyngeus muscle, palatoglossus muscle, tensor veli palatini muscle, middle constrictor muscle, and/or superior constrictor muscle.

[0161] Following the delivery of the neuromodulation signal, the palatal and pharyngeal musculature is again activated, as represented by block 1108. This second stage of muscle activation may further increase the tone of these muscles, enhancing the reduction or prevention of airway obstruction.

[0162] The method 1100 then proceeds to block 1110, which involves delivering a neuromodulation signal to a target site proximate to one or combinations of intrinsic tongue muscles (such as superior longitudinal, inferior longitudinal, transverse, or vertical muscles) and/or extrinsic tongue muscles (such as genioglossus, hyoglossus, or styloglossus). This leads to block 1112, which involves activating the intrinsic and/or extrinsic tongue musculature. [0163] The method 1100 then proceeds to block 1114, which involves delivering a neuromodulation signal to a target site proximate to a hypoglossal nerve that innervates a genioglossus muscle, and/or an ansa cervicalis nerve that innervates a strap muscle. This leads to block 1116, which involves activating the genioglossus muscle and/or strap muscle.

[0164] Finally, the method 1100 concludes with block 1118, which involves improving the patient's sleep disordered breathing via the delivery of the neuromodulation signal. The improvement in sleep disordered breathing may be manifested as a reduction in the frequency and severity of apnea or hypopnea events, an increase in the quality of sleep, a decrease in daytime sleepiness, and/or other improvements in the patient's condition. The method 1100 thus provides a novel and potentially effective approach for treating sleep disordered breathing, particularly in patients with obstructive sleep apnea and other forms of sleep disordered breathing.

[0165] Referring to FIG. 12, a flowchart illustrates a comprehensive method 1200 of treating sleep disordered breathing. The method 1200 begins with block 1202, which involves delivering a neuromodulation signal to a target site proximate to one or combinations of nerves that innervate the palatal and/or pharyngeal musculature. The nerves may include the lesser palatine nerve, the nerve to tensor veli palatini, and branches of the pharyngeal plexus that innervate the levator veli palatini, palatopharyngeus, palatoglossus, middle constrictor, and/or superior constrictor.

[0166] Upon delivery of the neuromodulation signal, the palatal and pharyngeal musculature is activated, as represented by block 1204. This activation may increase the tone of these muscles, potentially reducing or preventing airway obstruction during sleep.

[0167] The method 1200 then proceeds to block 1206, which involves delivering a neuromodulation signal to a target site proximate to one or combinations of specific palatal and pharyngeal muscles. These muscles may include the levator veli palatini muscle, musculus uvulae muscle, palatopharyngeus muscle, palatoglossus muscle, tensor veli palatini muscle, middle constrictor muscle, and/or superior constrictor muscle.

[0168] Following the delivery of the neuromodulation signal, the palatal and pharyngeal musculature is again activated, as represented by block 1208. This second stage of muscle activation may further increase the tone of these muscles, enhancing the reduction or prevention of airway obstruction.

[0169] The method 1200 then proceeds to block 1210, which involves delivering a neuromodulation signal to a target site proximate to one or combinations of intrinsic tongue muscles (such as superior longitudinal, inferior longitudinal, transverse, or vertical muscles) and/or extrinsic tongue muscles (such as genioglossus, hyoglossus, or styloglossus). This leads to block 1212, which involves activating the intrinsic and/or extrinsic tongue musculature.

[0170] The method 1200 then proceeds to block 1214, which involves delivering a neuromodulation signal to a target site proximate to a hypoglossal nerve that innervates a genioglossus muscle, and/or an ansa cervicalis nerve that innervates a strap muscle. This leads to block 1216, which involves activating the genioglossus muscle and/or strap muscle. [0171] Finally, the method 1200 concludes with block 1218, which involves improving the patient's sleep disordered breathing via the delivery of the neuromodulation signal. The improvement in sleep disordered breathing may be manifested as a reduction in the frequency and severity of apnea or hypopnea events, an increase in the quality of sleep, a decrease in daytime sleepiness, and/or other improvements in the patient's condition. The method 1200 thus provides a comprehensive and effective approach for treating sleep disordered breathing, particularly in patients with obstructive sleep apnea and other forms of sleep disordered breathing.

[0172] In some aspects, the methods and systems for treating sleep disordered breathing may involve delivering a neuromodulation signal to the target site. The neuromodulation signal may be of various forms, including but not limited to, an electrical signal, a magnetic signal, an ultrasound signal, a piezoelectric signal, a radiation signal, an electromagnetic signal, a radiofrequency signal, a mechanical signal, a chemical signal, an optical signal, a sound signal, or any combination thereof. The choice of the form of the neuromodulation signal may depend on various factors, such as the specific anatomy of the patient, the specific type of sleep disordered breathing being treated, the specific nerves or muscles being targeted, and the desired therapeutic outcome.

[0173] In some cases, the neuromodulation signal may be delivered continuously. In other cases, the neuromodulation signal may be delivered in successive pulse trains. The pulse trains may be of various forms, including but not limited to, square waves, sine waves, triangle waves, exponential waves, sawtooth waves, pulse waves, or any other suitable waveform. The choice of the form of the pulse trains may depend on various factors, such as the specific anatomy of the patient, the specific type of sleep disordered breathing being treated, the specific nerves or muscles being targeted, and the desired therapeutic outcome.

[0174] In some embodiments, the neuromodulation signal may be delivered with varying modulation parameters. The modulation parameters may include, but are not limited to, current amplitude, voltage amplitude, frequency, pulse width, duty cycle, pulse configuration, or any combination thereof. The modulation parameters may be adjusted to optimize the treatment outcome for each patient. For example, the current amplitude may be adjusted to achieve a desired level of nerve or muscle activation, the voltage amplitude may be adjusted to achieve a desired level of nerve or muscle activation, the frequency may be adjusted to achieve a desired level of nerve or muscle activation, the pulse width may be adjusted to achieve a desired level of nerve or muscle activation, the duty cycle may be adjusted to achieve a desired level of nerve or muscle activation, and the pulse configuration may be adjusted to achieve a desired level of nerve or muscle activation.

[0175] In some embodiments, the methods and systems for treating sleep disordered breathing may be configured as a closed-loop system. In a closed-loop system, the system may include sensors for sensing, measuring, and monitoring physiologic parameters and/or surrogates for sleep and/or sleep apnea and/or breathing. The sensed, measured, and monitored data may be used to adjust the delivery of the neuromodulation signal in real-time, thereby providing a dynamic and responsive treatment for sleep disordered breathing. [0176] In other embodiments, the methods and systems for treating sleep disordered breathing may be configured as an open-loop system. In an open-loop system, the neuromodulation parameters may be configured based upon polysomnographic data and/or data from a home sleep study and/or data from another form of sleep study. The configured neuromodulation parameters may then be used to deliver the neuromodulation signal in a predetermined manner, thereby providing a consistent and predictable treatment for sleep disordered breathing.

[0177] In some aspects, the methods and systems for treating sleep disordered breathing may involve a therapy delivery system placed internally in the oral and/or nasal cavity and/or oropharynx and/or nasopharynx. The therapy delivery system may include at least one electrode configured to deliver a neuromodulation signal to a target site that is a nerve or muscle. The therapy delivery system may also include a power source in wired or wireless communication with the electrode, and a controller in communication with the electrode. The controller may be programmed to direct delivery of an electrical or other signal by the electrode to the target site.

[0178] In some cases, the therapy delivery system may be implanted within the patient's body. The implantation of the therapy delivery system may involve a permucosal/transmucosal and/or percutaneous delivery technique. The delivery technique may involve the use of a catheter, cannula, sheath, or other conduit to guide the therapy delivery system to the target site. In some embodiments, the therapy delivery system may be implanted using a surgical procedure.

[0179] In some embodiments, the therapy delivery system may include an implantable receiver in communication with one or more implanted electrodes comprising the neurostimulator subsystem. The implantable receiver may be configured to receive a signal and power from the oral appliance subsystem. The signal and power may be transmitted from the oral appliance subsystem to the implantable receiver via a wired or wireless communication link. The implantable receiver may then deliver the neuromodulation signal to the target site via the one or more implanted electrodes.

[0180] In some cases, the target site may be proximate to a nerve that innervates a palatal muscle and/or a pharyngeal muscle. The nerve may be one or a combination of the lesser palatine nerve, the nerve to tensor veli palatini, and branches of the pharyngeal plexus that innervate the levator veli palatini, palatopharyngeus, palatoglossus, middle constrictor, and/or superior constrictor. The electrode may be positioned to deliver the neuromodulation signal to the target site in a manner that activates the nerve, thereby increasing the tone of the innervated muscle and potentially reducing or preventing airway obstruction during sleep.

[0181] In other cases, the target site may be a muscle that is the palatal muscle and/or the pharyngeal muscle. The muscle may be one or a combination of the levator veli palatini muscle, musculus uvulae muscle, palatopharyngeus muscle, palatoglossus muscle, tensor veli palatini muscle, middle constrictor muscle, and/or superior constrictor muscle. The electrode may be positioned to deliver the neuromodulation signal to the target site in a manner that activates the muscle, thereby increasing its tone and potentially reducing or preventing airway obstruction during sleep. 3.B. Neuromodulation Delivery System

[0182] The present disclosure provides methods and systems for treating sleep disordered breathing (SDB) conditions, such as obstructive sleep apnea (OSA), by delivering neuromodulation signals to specific nerves or muscles associated with the airway. The disclosed methods and systems may involve the use of an oral appliance subsystem, which may include one or more electrodes, a pulse generator, and a rechargeable battery. The electrodes may be configured to deliver neuromodulation signals to target sites proximate to certain nerves or muscles in the oral cavity, nasal cavity, oropharynx, and/or nasopharynx. These target sites may include, but are not limited to, the lesser palatine nerve, the nerve to tensor veli palatini, branches of the pharyngeal plexus, and various muscles of the palate, pharynx, and tongue. The pulse generator, powered by the rechargeable battery, may be programmed to regulate the delivery of the neuromodulation signals, which may be in the form of electrical, magnetic, ultrasound, piezoelectric, radiation, electromagnetic, radiofrequency, mechanical, chemical, optical, sound signals, or any combination thereof. The delivery of these signals may activate the motor fibers of the targeted nerves and/or the muscle fibers of the targeted muscles, thereby increasing their tone and potentially improving the patient's sleep disordered breathing. The disclosed methods and systems offer a novel approach to treating SDB, particularly in patients with certain phenotypes of OSA that are not well-treated by existing therapies.

[0183] Referring to FIG. 13, a system diagram 1300 illustrates a non-implantable neurostimulation system for treating sleep disordered breathing. The system includes a remote 1302, a retainer 1304, a pulse generator 1306, an electrode 1308, a charger 1310, a battery 1312, and an optional sensor 1314. [0184] The remote 1302 is a handheld device that allows a user, such as a patient or healthcare provider, to control the operation of the pulse generator 1306. The remote 1302 may include buttons, switches, or other user interface elements for adjusting the parameters of the neuromodulation signal, such as its amplitude, frequency, pulse width, and duty cycle. The remote 1302 may communicate with the pulse generator 1306 via a wired or wireless connection.

[0185] The retainer 1304 is a device designed to be worn in the oral cavity. It may be custom-fitted to the patient's dental arch and may include features for securing it in place, such as clasps or suction elements. The retainer 1304 houses the battery 1312 and is connected to the pulse generator 1306.

[0186] The pulse generator 1306 is a device that generates the neuromodulation signal. It is powered by the battery 1312 and is in electrical communication with the electrode 1308. The pulse generator 1306 may be programmed to generate a neuromodulation signal with specific parameters, such as a particular frequency, amplitude, pulse width, and duty cycle. These parameters may be adjusted based on input from the remote 1302.

[0187] The pulse generator 1306 may comprise a sophisticated microcontroller or control unit that allows for programming, monitoring, and adjustment of various stimulation parameters. This control unit may receive inputs from sensors, controllers, and the battery to optimize the stimulation delivery. In some aspects, the microcontroller may utilize adaptive algorithms to dynamically adjust stimulation parameters based on real-time feedback from sensors or user inputs via the remote control.

[0188] The pulse generator 1306 may also include a dedicated pulse generation circuit that creates electrical pulses with specific parameters such as amplitude, pulse width, frequency, and waveform shape. This circuit may receive instructions from the microcontroller and draw power from the battery to generate the desired stimulation pulses. In some cases, the pulse generator may be capable of producing complex waveforms or multiple independent stimulation channels.

[0189] The pulse generator 1306 may further incorporate an output stage or amplifier that amplifies the generated pulses and drives the current through the electrodes. This stage may ensure that the stimulation pulses have sufficient power to effectively stimulate the target tissues while maintaining safety limits. [0190] In some aspects, the pulse generator 1306 may be a single integrated unit encompassing multiple functions (e.g., a single printed circuit board).

[0191] The electrode 1308 is a component that delivers the neuromodulation signal to the target site. The electrode 1308 may be positioned within the retainer 1304 such that when the retainer is worn, the electrode is proximate to the target site. The electrode 1308 may be in wired or wireless communication with the pulse generator 1306.

[0192] The charger 1310 is a device for recharging the battery 1312. The charger 1310 may be a separate device that is connected to the retainer 1304, or it may be integrated into the retainer. The charger 1310 may use various methods to transfer power to the battery 1312, such as inductive charging, direct electrical connection, or other suitable methods.

[0193] The battery 1312 is a power source for the pulse generator 1306. The battery 1312 may be a rechargeable battery that can be recharged using the charger 1310. The battery 1312 may be housed within the retainer 1304.

[0194] The sensor 1314 is an optional component that may be included in some embodiments of the system. The sensor 1314 may be configured to sense a physiological and/or anatomical parameter and generate a sensor signal based on the sensed parameter. The sensor 1314 may be in wired or wireless communication with the pulse generator 1306. The controller, which may be part of the pulse generator 1306, may be programmed to direct delivery of the electrical signal to the target site by the electrode 1308 based on the sensor signal.

[0195] In some cases, the system may be configured as a closed-loop system. In a closed-loop system, the sensor 1314 senses physiologic parameters related to the patient's sleep disordered breathing, such as airflow, oxygen saturation, or muscle activity. The sensor 1314 generates a sensor signal based on these parameters, and the controller adjusts the parameters of the neuromodulation signal based on the sensor signal. This allows the system to automatically adjust the neuromodulation therapy in response to changes in the patient's condition.

[0196] In other cases, the system may be configured as an open-loop system. In an open-loop system, the parameters of the neuromodulation signal are set based on data from a polysomnographic study or other sleep study. The controller directs the delivery of the neuromodulation signal based on these preset parameters. The open-loop system may be suitable for patients whose sleep disordered breathing characteristics are relatively stable and predictable.

[0197] Referring to FIG. 14, a system diagram 1400 illustrates an implantable neurostimulation system for treating sleep disordered breathing. The system includes a remote 1402, a delivery system 1404, a retainer 1406, a pulse generator 1408, an electrode 1410, a charger 1412, a battery 1414, and an optional sensor 1416.

[0198] The remote 1402 is a handheld device that allows a user, such as a patient or healthcare provider, to control the operation of the pulse generator 1408. The remote 1402 may include buttons, switches, or other user interface elements for adjusting the parameters of the neuromodulation signal, such as its amplitude, frequency, pulse width, and duty cycle. The remote 1402 may communicate with the pulse generator 1408 via a wired or wireless connection.

[0199] The delivery system 1404 is an implantable device that includes at least one electrode 1410. The electrode 1410 is a submucosally implanted electrode that is configured to deliver the neuromodulation signal to the target site. The delivery system 1404 may be implanted using a variety of methods, such as percutaneous delivery, transmucosal delivery, or surgical placement.

[0200] The retainer 1406 is a device designed to be worn in the oral cavity. It may be custom-fitted to the patient's dental arch and may include features for securing it in place, such as clasps or suction elements. The retainer 1406 houses the battery 1414, which is connected to the pulse generator 1408.

[0201] The pulse generator 1408 is a device that generates the neuromodulation signal. It is powered by the battery 1414 and is in electrical communication with the electrode 1410. The pulse generator 1408 may be programmed to generate a neuromodulation signal with specific parameters, such as a particular frequency, amplitude, pulse width, and duty cycle. These parameters may be adjusted based on input from the remote 1402.

[0202] The charger 1412 is a device for recharging the battery 1414. The charger 1412 may be a separate device that is connected to the retainer 1406, or it may be integrated into the retainer. The charger 1412 may use various methods to transfer power to the battery 1414, such as inductive charging, direct electrical connection, or other suitable methods.

[0203] The battery 1414 is a power source for the pulse generator 1408. The battery 1414 may be a rechargeable battery that can be recharged using the charger 1412. The battery 1414 may be housed within the retainer 1406.

[0204] The sensor 1416 is an optional component that may be included in some embodiments of the system. The sensor 1416 may be configured to sense a physiological and/or anatomical parameter and generate a sensor signal based on the sensed parameter. The sensor 1416 may be in wired or wireless communication with the pulse generator 1408. The controller, which may be part of the pulse generator 1408, may be programmed to direct delivery of the electrical signal to the target site by the electrode 1410 based on the sensor signal.

[0205] In some cases, the system may be configured as a closed-loop system. In a closed-loop system, the sensor 1416 senses physiologic parameters related to the patient's sleep disordered breathing, such as airflow, oxygen saturation, or muscle activity. The sensor 1416 generates a sensor signal based on these parameters, and the controller adjusts the parameters of the neuromodulation signal based on the sensor signal. This allows the system to automatically adjust the neuromodulation therapy in response to changes in the patient's condition.

[0206] In other cases, the system may be configured as an open-loop system. In an open-loop system, the parameters of the neuromodulation signal are set based on data from a polysomnographic study or other sleep study. The controller directs the delivery of the neuromodulation signal based on these preset parameters. The open-loop system may be suitable for patients whose sleep disordered breathing characteristics are relatively stable and predictable.

[0207] Referring to FIG. 15, an oral appliance 1500 is depicted, designed for use in the oral cavity. The oral appliance 1500 integrates several components into a dental prosthesis structure, providing a compact and convenient solution for delivering neurostimulation therapy in the oral cavity.

[0208] The oral appliance 1500 includes a pulse generator and electrode 1502, a battery 1504, and a prosthetic structure 1506. The pulse generator and electrode 1502 are positioned within the prosthetic structure 1506. The pulse generator and electrode 1502 are responsible for generating and delivering the neuromodulation signal to the targeted nerves or muscles. The battery 1504, which provides power to the pulse generator and electrode 1502, is also integrated into the prosthetic structure 1506.

[0209] The prosthetic structure 1506 forms the main body of the oral appliance 1500. It is designed to fit the user's dental arch, providing a comfortable and secure fit. The prosthetic structure 1506 may be custom-fitted to the patient's dental arch and may include features for securing it in place, such as clasps or suction elements.

[0210] Wiring 1508 is shown connecting the prosthetic structure 1506 to the oral cavity. The wiring 1508 provides a conduit for the neuromodulation signal from the pulse generator and electrode 1502 to the targeted nerves or muscles.

[0211] In some cases, the oral appliance 1500 may be configured as a closed-loop system. In a closed- loop system, the oral appliance 1500 may include a sensor (not shown in FIG. 15) configured to sense a physiological and/or anatomical parameter and generate a sensor signal based on the sensed parameter. The controller, which may be part of the pulse generator and electrode 1502, may be programmed to direct delivery of the electrical signal to the target site by the electrode based on the sensor signal. This allows the system to automatically adjust the neuromodulation therapy in response to changes in the patient's condition.

[0212] In other cases, the oral appliance 1500 may be configured as an open-loop system. In an openloop system, the parameters of the neuromodulation signal are set based on data from a polysomnographic study or other sleep study. The controller directs the delivery of the neuromodulation signal based on these preset parameters. The open-loop system may be suitable for patients whose sleep disordered breathing characteristics are relatively stable and predictable. [0213] In some aspects, the oral appliance 1500 may be designed to be removable, allowing the patient to easily insert and remove the appliance as needed. This may provide the patient with greater flexibility and comfort, as well as facilitating cleaning and maintenance of the appliance.

[0214] In some cases, the oral appliance 1500 may be designed to be adjustable, allowing for customization of the fit and positioning of the appliance to suit the individual patient's anatomy and comfort preferences. This may enhance the effectiveness of the neuromodulation therapy by ensuring optimal positioning of the electrode 1502 in relation to the targeted nerves or muscles.

[0215] In some aspects, the oral appliance 1500 may be designed to be worn during sleep, providing neuromodulation therapy to improve sleep disordered breathing while the patient is sleeping. This may provide a convenient and non-invasive treatment option for patients with sleep disordered breathing conditions such as obstructive sleep apnea.

[0216] In some cases, the oral appliance 1500 may be designed to be used in conjunction with other treatments for sleep disordered breathing, such as continuous positive airway pressure (CPAP) therapy, mandibular advancement devices, or surgical interventions. This may provide a comprehensive and multifaceted approach to treating sleep disordered breathing.

[0217] In some aspects, the oral appliance 1500 may be designed to be used in a variety of settings, including at home, in a sleep lab, in a hospital, or in other healthcare facilities. This may provide flexibility and convenience for the patient, allowing them to receive neuromodulation therapy wherever it is most convenient and comfortable for them.

[0218] In some cases, the oral appliance 1500 may be designed to be used by a wide range of patients, including adults, children, and individuals with varying degrees of sleep disordered breathing severity. This may provide a versatile and adaptable treatment option that can be tailored to meet the specific needs of each individual patient.

[0219] In some aspects, the oral appliance 1500 may be designed to be used for both diagnostic and therapeutic purposes. For example, the oral appliance 1500 may be used to monitor the patient's sleep disordered breathing patterns and adjust the neuromodulation therapy parameters accordingly, providing a personalized and adaptive treatment approach.

[0220] In some cases, the oral appliance 1500 may be designed to be used for long-term treatment of sleep disordered breathing. The oral appliance 1500 may be durable and designed for repeated use, providing a sustainable and long-lasting treatment option for patients with chronic sleep disordered breathing conditions.

[0221] In some aspects, the oral appliance 1500 may be designed to be used for short-term treatment of sleep disordered breathing, such as during acute episodes or exacerbations of the condition. This may provide a rapid and effective treatment option for patients experiencing acute symptoms of sleep disordered breathing.

[0222] In some cases, the oral appliance 1500 may be designed to be used as a standalone treatment for sleep disordered breathing, providing a non-invasive and convenient alternative to other treatment options such as CPAP therapy or surgery. [0223] In some aspects, the oral appliance 1500 may be designed to be used as part of a comprehensive treatment plan for sleep disordered breathing, in conjunction with other treatments such as lifestyle modifications, medication, or other therapies. This may provide a holistic and multi-faceted approach to treating sleep disordered breathing.

[0224] Referring to FIG. 15, the oral appliance 1500 may be secured within the patient's oral cavity using various attachment methods and configurations. In some cases, the oral appliance 1500 may be molded to fit the patient's upper palate, mandible, or dentition. This custom-fit design may ensure a secure and comfortable fit, allowing the oral appliance 1500 to stay in place during sleep and deliver effective neuromodulation therapy.

[0225] In other cases, the oral appliance 1500 may be mechanically attached to the patient's craniofacial anatomy. For example, the oral appliance 1500 may be attached using wiring or other mechanical fasteners. This mechanical attachment may provide a secure and stable positioning of the oral appliance 1500, ensuring consistent delivery of the neuromodulation signal to the targeted nerves or muscles.

[0226] In some aspects, the oral appliance 1500 may be attached to the oral, pharyngeal, or nasal mucosa. This may involve the use of adhesives or other suitable attachment methods. By attaching the oral appliance 1500 to the mucosa, the appliance may be positioned in close proximity to the targeted nerves or muscles, facilitating effective delivery of the neuromodulation signal.

[0227] In some cases, the oral appliance 1500 may be designed with a combination of these attachment methods. For example, the oral appliance 1500 may be custom-molded to fit the patient's dentition and also mechanically attached to the patient's craniofacial anatomy. This combination of attachment methods may provide a secure and comfortable fit, while also ensuring optimal positioning of the oral appliance 1500 for effective delivery of the neuromodulation therapy.

[0228] In some aspects, the oral appliance 1500 may be designed to be easily removable, allowing the patient to insert and remove the appliance as needed. This may provide the patient with greater flexibility and comfort, as well as facilitating cleaning and maintenance of the appliance.

[0229] In some cases, the oral appliance 1500 may be designed to be adjustable, allowing for customization of the fit and positioning of the appliance to suit the individual patient's anatomy and comfort preferences. This may enhance the effectiveness of the neuromodulation therapy by ensuring optimal positioning of the electrode 1502 in relation to the targeted nerves or muscles.

[0230] Referring to FIG. 16A, an oral appliance 1600A is depicted, designed for use in the oral cavity.

The oral appliance 1600A integrates several components into a dental prosthesis structure 1606, providing a compact and convenient solution for delivering neurostimulation therapy in the oral cavity.

[0231] The oral appliance 1600A includes a pulse generator and electrodes 1602, a battery 1604, and a prosthetic structure 1606. The pulse generator and electrodes 1602 are positioned within the prosthetic structure 1606. The pulse generator and electrodes 1602 are responsible for generating and delivering the neuromodulation signal to the targeted nerves or muscles. The battery 1604, which provides power to the pulse generator and electrodes 1602, is also integrated into the prosthetic structure 1606. [0232] The prosthetic structure 1606 forms the main body of the oral appliance 1600A. It is designed to fit the user's dental arch, providing a comfortable and secure fit. The prosthetic structure 1606 may be custom-fitted to the patient's dental arch and may include features for securing it in place, such as clasps or suction elements.

[0233] Wiring 1608 is shown connecting the prosthetic structure 1606 to the oral cavity. The wiring 1608 provides a conduit for the neuromodulation signal from the pulse generator and electrodes 1602 to the targeted nerves or muscles.

[0234] In some aspects, the oral appliance 1600A may be designed to be removable, allowing the patient to easily insert and remove the appliance as needed. This may provide the patient with greater flexibility and comfort, as well as facilitating cleaning and maintenance of the appliance.

[0235] In some cases, the oral appliance 1600A may be designed to be adjustable, allowing for customization of the fit and positioning of the appliance to suit the individual patient's anatomy and comfort preferences. This may enhance the effectiveness of the neuromodulation therapy by ensuring optimal positioning of the electrode 1602 in relation to the targeted nerves or muscles.

[0236] In some aspects, the oral appliance 1600A may be designed to deliver the neuromodulation signal through an oral approach. In this case, the electrode 1602 may be positioned within the oral cavity, in proximity to the targeted nerves or muscles. This may allow for direct delivery of the neuromodulation signal to the targeted nerves or muscles, potentially enhancing the effectiveness of the therapy.

[0237] In other cases, the oral appliance 1600A may be designed to deliver the neuromodulation signal through a nasal approach. In this case, the electrode 1602 may be positioned within the nasal cavity, in proximity to the targeted nerves or muscles. This may allow for direct delivery of the neuromodulation signal to the targeted nerves or muscles, potentially enhancing the effectiveness of the therapy.

[0238] In some aspects, the oral appliance 1600A may be designed to deliver the neuromodulation signal to a target site that is a nerve or muscle. The target site may be proximate to a nerve or muscle that is involved in maintaining upper airway patency, such as the palatoglossus muscle 1610 or the palatopharyngeus muscle 1612. By delivering the neuromodulation signal to these target sites, the oral appliance 1600A may help to improve the patient's sleep disordered breathing.

[0239] Referring to FIG. 16B, a side view of an oral appliance 1600B is depicted, designed for use in the oral cavity. The oral appliance 1600B integrates several components into a dental prosthesis structure 1606, providing a compact and convenient solution for delivering neurostimulation therapy in the oral cavity.

[0240] The oral appliance 1600B includes a pulse generator and electrodes 1602, a battery 1604, and a prosthetic structure 1606. The pulse generator and electrodes 1602 are positioned within the prosthetic structure 1606. The pulse generator and electrodes 1602 are responsible for generating and delivering the neuromodulation signal to the targeted nerves or muscles. The battery 1604, which provides power to the pulse generator and electrodes 1602, is also integrated into the prosthetic structure 1606.

[0241] The prosthetic structure 1606 forms the main body of the oral appliance 1600B. It is designed to fit the user's dental arch, providing a comfortable and secure fit. The prosthetic structure 1606 may be custom-fited to the patient's dental arch and may include features for securing it in place, such as clasps or suction elements.

[0242] Wiring 1608 is shown connecting the prosthetic structure 1606 to the oral cavity. The wiring 1608 provides a conduit for the neuromodulation signal from the pulse generator and electrodes 1602 to the targeted nerves or muscles.

[0243] In some aspects, the oral appliance 1600B may be designed to be removable, allowing the patient to easily insert and remove the appliance as needed. This may provide the patient with greater flexibility and comfort, as well as facilitating cleaning and maintenance of the appliance.

[0244] In some cases, the oral appliance 1600B may be designed to be adjustable, allowing for customization of the fit and positioning of the appliance to suit the individual patient's anatomy and comfort preferences. This may enhance the effectiveness of the neuromodulation therapy by ensuring optimal positioning of the electrode 1602 in relation to the targeted nerves or muscles.

[0245] In some aspects, the oral appliance 1600B may be designed to deliver the neuromodulation signal through an oral approach. In this case, the electrode 1602 may be positioned within the oral cavity, in proximity to the targeted nerves or muscles. This may allow for direct delivery of the neuromodulation signal to the targeted nerves or muscles, potentially enhancing the effectiveness of the therapy.

[0246] In other cases, the oral appliance 1600B may be designed to deliver the neuromodulation signal through a nasal approach. In this case, the electrode 1602 may be positioned within the nasal cavity, in proximity to the targeted nerves or muscles. This may allow for direct delivery of the neuromodulation signal to the targeted nerves or muscles, potentially enhancing the effectiveness of the therapy.

[0247] In some aspects, the oral appliance 1600B may be designed to deliver the neuromodulation signal to a target site that is a nerve or muscle. The target site may be proximate to a nerve or muscle that is involved in maintaining upper airway patency, such as the palatoglossus muscle 1610 or the palatopharyngeus muscle 1612. By delivering the neuromodulation signal to these target sites, the oral appliance 1600B may help to improve the patient's sleep disordered breathing. The application of the delivery system used to improve upper airway patency may involve the use of an oral appliance subsystem, which may include one or more electrodes, a pulse generator, and a rechargeable batery. The electrodes may be configured to deliver neuromodulation signals to target sites proximate to certain nerves or muscles in the oral cavity, nasal cavity, oropharynx, and/or nasopharynx. These target sites may include, but are not limited to, the lesser palatine nerve, the nerve to tensor veli palatini, branches of the pharyngeal plexus, and various muscles of the palate, pharynx, and tongue. The pulse generator, powered by the rechargeable batery, may be programmed to regulate the delivery of the neuromodulation signals, which may be in the form of electrical, magnetic, ultrasound, piezoelectric, radiation, electromagnetic, radiofrequency, mechanical, chemical, optical, sound signals, or any combination thereof. The delivery of these signals may activate the motor fibers of the targeted nerves and/or the muscle fibers of the targeted muscles, thereby increasing their tone and potentially improving the patient's sleep disordered breathing. The disclosed methods and systems may offer a novel approach to treating SDB, particularly in patients with certain phenotypes of OSA that are not well-treated by existing therapies. [0248] Referring to FIG. 17, a perspective view of a charging and control system 1700 for an oral appliance is illustrated. The system comprises a charging case 1702 and a remote control 1704. The charging case 1702 has a hinged lid design and contains a compartment sized to accommodate an oral appliance 1700. The oral appliance 1700 is shown placed inside the open charging case 1702. On the charging case 1702 is the remote control 1704, which is integrated into the lid of the charging case. The remote control 1704 includes control buttons for operating the oral appliance system. This compact design allows for convenient storage, charging, and control of the oral appliance 1700 in a single integrated unit. [0249] In some aspects, the charging case 1702 may include charging pads or bowls for wireless charging of the oral appliance 1700. The charging pads or bowls may use tightly coupled electromagnetic resonant inductive or non-radiative charging, loosely coupled or radiative electromagnetic resonant charging, uncoupled radio frequency (RF) wireless charging, or any combination thereof to transfer energy from the charging case 1702 to the oral appliance 1700. This wireless charging feature may provide a convenient and efficient way to recharge the battery of the oral appliance 1700, eliminating the need for direct electrical connections and facilitating the use of the oral appliance 1700 in various settings. [0250] The remote control 1704 can be used to initiate, terminate, regulate, optimize, and modulate therapy delivered by the oral appliance 1700. The remote control 1704 may communicate with the oral appliance 1700 via a wired or wireless connection, allowing the user to control the operation of the oral appliance 1700 from a distance. The remote control 1704 may include buttons, switches, or other user interface elements for adjusting the parameters of the neuromodulation signal, such as its amplitude, frequency, pulse width, and duty cycle. The remote control 1704 may also include display elements, such as LEDs or an LCD screen, to provide visual feedback to the user about the status of the oral appliance 1700 and the neuromodulation therapy.

[0251] In some cases, the delivery of the electrical signal by the oral appliance 1700 may be initiated by removing the oral appliance 1700 from the charging case 1702 and/or pressing an activation button with a timer on the remote control 1704. This feature may provide a convenient and intuitive way for the user to start the neuromodulation therapy, and the timer function may allow the user to schedule the start of the therapy to coincide with their sleep schedule.

[0252] In some aspects, the charging case 1702 and the remote control 1704 may also function as a data management system for the oral appliance 1700. The charging case 1702 and the remote control 1704 may include memory for storing data related to the use of the oral appliance 1700, such as usage times, neuromodulation parameters, sensor data, and battery charge levels. The charging case 1702 and the remote control 1704 may also include data communication interfaces, such as USB ports or wireless communication modules, for transferring the stored data to a computer or other device for further analysis or reporting. This data management feature may provide valuable information to the user and their healthcare provider about the effectiveness of the neuromodulation therapy and the usage patterns of the oral appliance 1700.

[0253] In some aspects, the neuromodulation signal delivered by the oral appliance may comprise successive pulse trains. The pulse generator, which may be integrated into the oral appliance, can be programmed to deliver varying modulation parameters, including current amplitude, voltage amplitude, frequency, pulse width, duty cycle, and pulse configuration. These parameters may be adjusted based on input from the remote control, allowing for customization of the neuromodulation therapy to suit the individual patient's needs and condition.

[0254] The electrical signal delivered by the oral appliance may be continuous or in the form of successive pulse trains. These pulse trains may take various forms, including square waves, sine waves, triangle waves, exponential waves, sawtooth waves, pulse waves, or arbitrary waveforms. The choice of waveform may depend on the specific characteristics of the targeted nerves or muscles, the patient's condition, and the desired therapeutic effect.

[0255] In some cases, the initiation of the delivery of the electrical signal may be triggered by various mechanisms. For example, the delivery of the electrical signal may be initiated by optical sensing of device placement, proprioceptive sensing of device placement, mechanical sensing of device placement, moisture sensing, chemical sensing, physical patient orientation, stillness of body, and/or time of day. These initiation mechanisms may provide a convenient and intuitive way for the user to start the neuromodulation therapy, and may also allow for automatic adjustment of the therapy based on changes in the patient's condition or environment. For instance, the delivery of the electrical signal may be automatically initiated when the patient lies down to sleep, based on the detected change in physical patient orientation.

[0256] In some aspects, the oral appliance 1500, 1600A, 1600B, or 1700 may include a sensor 1314, 1416 configured to sense a physiological and/or anatomical parameter associated with sleep disordered breathing. The sensor 1314, 1416 may be in wired or wireless communication with the pulse generator 1306, 1408. The physiological and/or anatomical parameters that may be sensed by the sensor 1314, 1416 may include, but are not limited to, acoustic vibration, mechanical vibration, airflow parameters, blood flow parameters, heart rate, oxygen saturation, muscle activity, and/or nerve activity. These parameters may provide valuable information about the patient's sleep disordered breathing condition, and may be used to adjust the parameters of the neuromodulation signal to optimize the effectiveness of the therapy. [0257] In some cases, the sensor 1314, 1416 may be located within or near to the airway, vasculature, musculature, nerve pathways, and/or mucosa. The specific location of the sensor 1314, 1416 may depend on the specific physiological and/or anatomical parameter being sensed, as well as the specific nerve or muscle being targeted by the neuromodulation signal. For example, if the sensor 1314, 1416 is configured to sense airflow parameters, it may be located within the airway. If the sensor 1314, 1416 is configured to sense muscle activity, it may be located near to the targeted muscle. The sensor 1314, 1416 may be positioned in such a way as to provide accurate and reliable sensing of the physiological and/or anatomical parameter, while also minimizing discomfort or interference with the patient's normal activities.

[0258] In some aspects, the controller, which may be part of the pulse generator 1306, 1408, may be programmed to direct delivery of the electrical signal to the target site by the electrode 1308, 1410 based on the sensor signal. The controller may include software configured to analyze the sensor signal and adjust the parameters of the neuromodulation signal accordingly. For example, the controller may adjust the amplitude, frequency, pulse width, and/or duty cycle of the neuromodulation signal based on changes in the sensed physiological and/or anatomical parameter. This may allow the system to automatically adjust the neuromodulation therapy in response to changes in the patient's condition, potentially enhancing the effectiveness of the therapy.

[0259] In some cases, the controller may be configured to analyze the sensor signal in real-time, allowing for immediate adjustment of the neuromodulation signal based on changes in the sensed physiological and/or anatomical parameter. In other cases, the controller may be configured to store the sensor signal for later analysis, allowing for retrospective adjustment of the neuromodulation signal based on trends or patterns in the sensed physiological and/or anatomical parameter. The specific configuration of the controller and its software may depend on the specific requirements of the neuromodulation therapy, as well as the specific characteristics of the patient's sleep disordered breathing condition.

[0260] The present disclosure relates to methods and systems for treating sleep disordered breathing, such as obstructive sleep apnea. The methods and systems may involve the delivery of a neuromodulation signal to specific nerves or muscles associated with airway obstruction during sleep. The neuromodulation signal may be delivered via an electrode or electrodes configured to target specific sites within the oral and/or nasal cavity, oropharynx, and/or nasopharynx. The delivery system may include a power source and a controller, which may be programmed to direct the delivery of the neuromodulation signal. The system may also include sensors for monitoring various physiological parameters, enabling personalized treatment and improved patient compliance. The disclosure further encompasses methods and systems for treating sleep disordered breathing by delivering a neuromodulation signal to a target site where that target site is a palatal muscle and/or pharyngeal muscle, or nerve that innervates a palatal muscle and/or a pharyngeal muscle. The disclosure also provides methods and systems for improving sleep disordered breathing in a patient suffering therefrom by activating the palatal and pharyngeal musculature by neuromodulation. The methods and systems may be designed, manufactured, built, constructed, formed, assembled, shaped, molded, fabricated or produced such that electrodes are placed according to specific patient anatomy in order to achieve airway opening and optimal improvement in a patient’s sleep disordered breathing.

[0261] Referring to FIG. 18, the figure illustrates a neuromodulation therapy system 1800 for treating sleep disordered breathing. The system 1800 includes a first electrode 1802 and a second electrode 1810. The first electrode 1802 is positioned on or near the palatoglossus muscle 1806 and the palatopharyngeus muscle 1808. The second electrode 1810 is positioned near a third molar tooth 1820. The electrodes 1802 and 1810 are configured to deliver a neuromodulation signal, as indicated by the neuromodulation flow direction 1804.

[0262] In some aspects, the second electrode 1810 may be positioned at the superomedial insertion 1812 of the palatoglossus muscle 1806, while the first electrode 1802 may be positioned on the retromolar trigone. This configuration allows the neuromodulation signal to be sent along the length of the palatoglossus muscle 1806, improving the patient's sleep disordered breathing. [0263] In other cases, the second electrode 1810 may be positioned at the superomedial insertion 1814 of the palatopharyngeus muscle 1808, while the first electrode 1802 may be positioned on a device component placed over the third molar tooth 1820. This configuration allows the neuromodulation signal to be sent along the length of the palatoglossus muscle 1806 to a fixed point secured on a mandibular tooth. In this embodiment, a non-conductive coating 1840 may be in contact with the tooth, and the second electrode 1810 may be embedded into the non-conductive coating 1840. This arrangement may prevent modulation of dental pulp nerves, the inferior alveolar nerve, or any nerve that is not intended to be modulated.

[0264] In yet another aspect, the first electrode 1802 may be positioned at the superomedial insertion of the palatoglossus muscle 1806, while the second electrode 1810 may be positioned at the glossal insertion of the palatoglossus muscle 1806. This configuration allows the neuromodulation signal to be sent along the length of the palatoglossus muscle 1806, potentially improving the patient's sleep disordered breathing.

[0265] The neuromodulation therapy system 1800 may be part of a larger system that includes a power source and a controller. The power source may be in wired or wireless communication with the electrodes 1802 and 1810, and the controller may be in communication with the electrodes 1802 and 1810. The controller may be programmed to direct the delivery of the neuromodulation signal by the electrodes 1802 and 1810 to the target site, which may be a nerve or muscle. The delivery of the neuromodulation signal may improve the patient's sleep disordered breathing.

[0266] Referring to FIG. 19, the figure illustrates a neuromodulation therapy system 1900 for treating sleep disordered breathing. The system 1900 includes electrodes 1912 and 1924 positioned in relation to various muscles and structures of the soft palate and pharynx. The electrodes 1912 and 1924 are configured to deliver a neuromodulation signal to specific target sites, as indicated by the direction of neuromodulation flow 1922.

[0267] In some aspects, the electrode 1912 may be positioned near the tensor veli palatini muscle 1914. The tensor veli palatini muscle 1914 is a broad, thin, ribbon-like muscle in the soft palate, which plays a role in opening the Eustachian tube to allow equalization of pressure between the middle ear and the atmosphere. By delivering a neuromodulation signal to this muscle, the system 1900 may improve airway patency during sleep.

[0268] The electrode 1924 is positioned on or near the third molar tooth 1926. This placement allows for the delivery of a neuromodulation signal in close proximity to the oral and pharyngeal muscles, potentially improving the patient's sleep disordered breathing.

[0269] The system 1900 also depicts various muscles and structures of the soft palate and pharynx, including the musculus uvulae 1902, levator veli palatini muscle 1904, palatine aponeurosis 1906, superomedial insertion of palatopharyngeus 1908, and superomedial insertion of palatoglossus 1910. These structures are potential targets for the neuromodulation signal, and their activation may contribute to maintaining airway patency during sleep. [0270] In some cases, the electrodes 1912 and 1924 may be configured to deliver a neuromodulation signal to the palatopharyngeus muscle 1916 and the palatoglossus muscle 1920. These muscles play a crucial role in the function of the soft palate and the pharynx, and their activation may potentially improve airway function in patients with sleep disordered breathing.

[0271] In other aspects, the system 1900 may be configured to deliver a neuromodulation signal to the levator veli palatini muscle 1904. This muscle is the primary elevator of the soft palate and plays a key role in preventing nasopharyngeal reflux during swallowing. By delivering a neuromodulation signal to this muscle, the system 1900 may potentially improve the patient's sleep disordered breathing.

[0272] The arrangement of the electrodes 1912 and 1924 allows for targeted stimulation of the palatal and pharyngeal muscles. This configuration is designed to activate the muscles and potentially improve airway function in patients with sleep disordered breathing. The system 1900 may be part of a larger system that includes a power source and a controller, which may be programmed to direct the delivery of the neuromodulation signal. The delivery of the neuromodulation signal may improve the patient's sleep disordered breathing.

[0273] Referring to FIG. 20, the figure illustrates a neuromodulation therapy system 2000 for treating sleep disordered breathing. The system 2000 includes electrode arrays 2004 positioned along the soft palate, extending laterally from the center. The levator veli palatini muscles 2006 are depicted on either side of the soft palate, connecting to the palatine aponeurosis 2008. The superomedial insertion of the palatopharyngeus 2010 and the superomedial insertion of the palatoglossus 2012 are indicated at the lateral edges of the soft palate. An electrode array 2014 is positioned near these insertions.

[0274] In some aspects, the electrode arrays 2004 may be positioned along the soft palate, extending laterally from the center. This configuration allows for the delivery of a neuromodulation signal across a broad area of the soft palate, potentially improving the patient's sleep disordered breathing by activating multiple muscles simultaneously.

[0275] The tensor veli palatini muscle 2016 is shown lateral to the soft palate. The palatopharyngeus muscle 2018 and the palatoglossus muscle 2020 are depicted extending downward from the soft palate. Arrows indicating the direction of neuromodulation flow 2022 are shown emanating from the electrode arrays 2004 and 2014, indicating the path of electrical stimulation through the surrounding tissues.

[0276] The neuromodulation therapy system 2000 may be part of a larger system that includes a power source and a controller. The power source may be in wired or wireless communication with the electrode arrays 2004 and 2014, and the controller may be in communication with the electrode arrays 2004 and 2014. The controller may be programmed to direct the delivery of the neuromodulation signal by the electrode arrays 2004 and 2014 to the target site, which may be a nerve or muscle. The delivery of the neuromodulation signal may improve the patient's sleep disordered breathing.

[0277] Referring to FIG. 21, the figure illustrates a sagittal view of a neuromodulation therapy system 2100 implemented in the oral and pharyngeal regions. The system 2100 includes multiple electrodes 2106 and 2116 positioned in relation to various muscles and structures of the soft palate and pharynx. The electrodes 2106 and 2116 are configured to deliver a neuromodulation signal to specific target sites, as indicated by the direction of the neuromodulation signal 2108.

[0278] In some aspects, the electrodes 2106 may be positioned near the tongue base 2104. This placement allows for the delivery of a neuromodulation signal in close proximity to the oral and pharyngeal muscles, potentially improving the patient's sleep disordered breathing. The electrode 2116 is positioned near the junction of the hard palate 2118 and the soft palate . This placement allows for the delivery of a neuromodulation signal to the palatopharyngeus muscle 2112 and the palatoglossus muscle 2110, which are potential targets for the neuromodulation signal. These muscles, along with the uvula 2114, play a crucial role in the function of the soft palate and the pharynx, and their activation may potentially improve airway function in patients with sleep disordered breathing.

[0279] In other cases, the system 2100 may be configured to deliver a neuromodulation signal to the levator veli palatini muscle 1904. This muscle is the primary elevator of the soft palate and plays a key role in preventing nasopharyngeal reflux during swallowing. By delivering a neuromodulation signal to this muscle, the system 2100 may improve the patient's sleep disordered breathing.

[0280] The arrangement of the electrodes 2106 and 2116 allows for targeted stimulation of the palatal and pharyngeal muscles. This configuration is designed to activate the muscles and potentially improve airway function in patients with sleep disordered breathing. The system 2100 may be part of a larger system that includes a power source and a controller, which may be programmed to direct the delivery of the neuromodulation signal. The delivery of the neuromodulation signal may improve the patient's sleep disordered breathing.

[0281] Referring to FIG. 22, the figure illustrates an exploded view of a neuromodulation therapy system 2200. The system 2200 includes a retainer 2202, an electrode 2210, an electronics module 2212, and a cover 2214. The retainer 2202 is designed to fit within a patient's oral cavity and may be custom-molded to the patient's dentition for a secure and comfortable fit. The retainer 2202 includes an electrode hole 2204, which is positioned to allow the electrode 2210 to contact the patient at a specific location.

[0282] The electrode 2210 is configured to deliver a neuromodulation signal to a target site that is a nerve or muscle. The electrode 2210 is connected to the electronics module 2212, which contains a power source and a pulse generator. The power source may be a rechargeable battery, and it may be in wired or wireless communication with the electrode 2210. The pulse generator is configured to generate the neuromodulation signal based on programmed parameters.

[0283] The electronics module 2212 is enclosed within the retainer 2202 and is protected by the cover 2214. The cover 2214 is designed to fit securely over the electronics module 2212, protecting it from damage and exposure to the oral environment.

[0284] On the surface of the electronics module 2212 is a status LED 2206 that serves as an on/off button and indicator. Adjacent to the status LED 2206 is a charging contact 2208 for powering the device. The charging contact 2208 allows for the transfer of energy from an external power source to the power source within the electronics module 2212. [0285] In some aspects, the neuromodulation therapy system 2200 may be part of a larger system that includes a charging case and remote subsystem. The charging case and remote subsystem may be configured to transfer energy to the oral appliance subsystem while the oral appliance subsystem is docked within and/or on top of and/or proximal to the electromagnetic field of the charging case and remote subsystem. The case and remote subsystem may also function as a programming device that may be used to initiate, terminate, regulate, optimize, and/or modulate therapy delivered by the oral appliance and neurostimulator subsystems via a bidirectional wired or wireless telemetry link.

[0286] In some cases, the neuromodulation therapy system 2200 may be delivered in a retainer, nonretainer form, stent form, non-implant form, or implant form. The specific form may be selected based on the patient's anatomy, the specific target site for neuromodulation, and other factors. The system 2200 may be designed, manufactured, built, constructed, formed, assembled, shaped, molded, fabricated, or produced such that the electrode 2210 is placed according to specific patient anatomy in order to achieve airway opening and optimal improvement in a patient’s sleep disordered breathing.

[0287] Referring to FIG. 23, the figure illustrates a top view of a neuromodulation therapy system 2300. The system 2300 comprises a retainer 2304 shaped to fit over a dental arch. The retainer 2304 includes an electrode array 2306 positioned on its inner surface. The electrode array 2306 consists of multiple circular electrodes arranged in a grid pattern. Two batteries 2302 are integrated into the retainer 2304, one on each side of the electrode array 2306. The batteries 2302 are depicted as circular components embedded within the structure of the retainer 2304.

[0288] In some aspects, the retainer 2304 may be custom-molded to fit the patient's dentition for a secure and comfortable fit. The retainer 2304 may be designed to conform to the shape of the upper teeth and palate, with indentations visible for accommodating individual teeth. The retainer 2304 may be made of a biocompatible material that is durable, flexible, and resistant to the oral environment.

[0289] The electrode array 2306 may be configured to deliver a neuromodulation signal to specific target sites within the oral and/or nasal cavity, oropharynx, and/or nasopharynx. The electrode array 2306 may include multiple electrodes arranged in a specific pattern to optimize the delivery of the neuromodulation signal. The electrodes in the array 2306 may be independently controlled to deliver a neuromodulation signal to specific target sites, allowing for targeted stimulation of the palatal and pharyngeal muscles.

[0290] The batteries 2302 may be rechargeable and may provide power to the electrode array 2306. The batteries 2302 may be positioned on either side of the electrode array 2306 to balance the weight of the retainer 2304 and to optimize the distribution of power to the electrodes.

[0291] In some cases, the neuromodulation therapy system 2300 may be part of a larger system that includes a power source and a controller. The power source may be in wired or wireless communication with the electrode array 2306, and the controller may be in communication with the electrode array 2306. The controller may be programmed to direct the delivery of the neuromodulation signal by the electrode array 2306 to the target site, which may be a nerve or muscle. The delivery of the neuromodulation signal may improve the patient's sleep disordered breathing. [0292] In other aspects, the neuromodulation therapy system 2300 may be delivered in a retainer, nonretainer form, stent form, non-implant form, or implant form. The specific form may be selected based on the patient's anatomy, the specific target site for neuromodulation, and other factors. The system 2300 may be designed, manufactured, built, constructed, formed, assembled, shaped, molded, fabricated, or produced such that the electrode array 2306 is placed according to specific patient anatomy in order to achieve airway opening and optimal improvement in a patient’s sleep disordered breathing.

[0293] In some aspects, the neuromodulation therapy system 1800, 1900, 2000, 2100, 2200, 2300 may deliver a neuromodulation signal that can be of various types. The neuromodulation signal may be an electrical signal, a magnetic signal, an ultrasound signal, a piezoelectric signal, a radiation signal, an electromagnetic signal, a radiofrequency signal, a mechanical signal, a chemical signal, an optical signal, a sound signal, or any combination thereof. The type of neuromodulation signal used may depend on the specific requirements of the patient's condition, the target site, and the desired therapeutic effect.

[0294] In some cases, the electrode or electrodes of the neuromodulation therapy system 1800, 1900, 2000, 2100, 2200, 2300 may be placed in various locations within the patient's body to deliver the neuromodulation signal. The electrode or electrodes may be placed internally in the head and/or neck, at or beneath or within a mucosal layer, at or beneath or within skin and/or a skin layer, at or beneath or within a muscle, at or in contact with a nerve or nerve fibers, at or within a blood vessel, at or within or in contact with soft tissue including a tendon and/or ligament and/or fascia and/or lymph node and/or adipose tissue. The specific placement of the electrode or electrodes may depend on the target site for neuromodulation and the specific requirements of the patient's condition.

[0295] In other aspects, the neuromodulation therapy system 1800, 1900, 2000, 2100, 2200, 2300 may deliver the neuromodulation signal via various delivery methods. The neuromodulation signal may be delivered via permucosal/transmucosal and/or percutaneous delivery, via a needle delivery system, catheter delivery system, introducer delivery system, sheath delivery system, dilator delivery system, guidewire delivery system, balloon catheter delivery system, stent delivery system, microcatheter delivery system, image guided delivery system, endoscopic delivery system, or optical delivery system. The specific delivery method used may depend on the target site for neuromodulation, the type of neuromodulation signal used, and the specific requirements of the patient's condition.

[0296] In yet other cases, the neuromodulation therapy system 1800, 1900, 2000, 2100, 2200, 2300 may deliver the neuromodulation signal with varying signal parameters. The signal parameters may include current amplitude, voltage amplitude, frequency, pulse width, duty cycle, and pulse configuration. The current amplitude may be delivered in the range of 0.01mA to 1A. The voltage amplitude may be delivered in the range of 0.0 IV to 250V. The frequency may be delivered in the range of 0.01Hz to 10kHz. The pulse width may be delivered in the range of O.Olps to 600s. The duty cycle may be delivered in the range of 0% to 100%. The pulse configuration may be delivered in any configuration to achieve suitable results, including voltage amplitude ramp-up, current amplitude ramp up, voltage amplitude stepdown, current amplitude step-down, variable pulse widths, variable duty cycles, variable current amplitudes, variable voltage amplitudes, sine-wave configurations, square-wave configurations, triangle wave configuration, exponential wave configurations, sawtooth wave configurations, pulse wave configurations, arbitrary wave configurations, in temporal patterns, in temporal sequences, in random patterns, in random sequences, and/or any combination therein. The specific signal parameters used may depend on the target site for neuromodulation, the type of neuromodulation signal used, and the specific requirements of the patient's condition.

[0297] In some aspects, the neuromodulation therapy system 1800, 1900, 2000, 2100, 2200, 2300 may operate in a closed-loop configuration. In this configuration, the system may include one or more sensors for sensing and monitoring various physiologic parameters related to sleep and breathing. These parameters may include, but are not limited to, respiratory rate, heart rate, blood oxygen levels, and muscle activity. The sensed data may be processed by a processor within the system, which may then control the delivery of the neuromodulation signal based on the processed data. For example, the processor may adjust the neuromodulation signal parameters, such as current amplitude, voltage amplitude, frequency, pulse width, duty cycle, and pulse configuration, in response to changes in the sensed physiologic parameters. This closed-loop configuration allows for real-time adjustment of the neuromodulation therapy, potentially improving the efficacy of the therapy and the patient's sleep disordered breathing.

[0298] In other cases, the neuromodulation therapy system 1800, 1900, 2000, 2100, 2200, 2300 may operate in an open-loop configuration. In this configuration, the neuromodulation signal parameters may be pre-configured based on data obtained from polysomnographic studies, home sleep studies, or other forms of sleep study or anatomical assessment. For example, the neuromodulation signal parameters may be set to target specific nerves or muscles identified as contributing to the patient's sleep disordered breathing based on the study or assessment data. The open-loop configuration allows for personalized treatment of the patient's sleep disordered breathing based on their specific condition and needs.

[0299] In some aspects, the neuromodulation therapy system 1800, 1900, 2000, 2100, 2200, 2300 may be incorporated into or combined with other therapies for treating sleep disordered breathing. For example, the system may be used in conjunction with continuous positive airway pressure (CPAP) therapy, where the CPAP therapy provides a constant flow of air to keep the patient's airway open during sleep, and the neuromodulation therapy system provides targeted stimulation to specific nerves or muscles to further improve airway patency. In another example, the system may be used in conjunction with a mandibular advancement device, which repositions the lower jaw forward to open up the airway, with the neuromodulation therapy system providing additional stimulation to the palatal and pharyngeal muscles to further improve airway patency. In yet another example, the system may be used as an adjunct to surgical interventions for sleep disordered breathing, providing neuromodulation therapy to enhance the effects of the surgical intervention and potentially improve the patient's sleep disordered breathing. The combination of the neuromodulation therapy system with other therapies allows for a comprehensive and personalized approach to treating sleep disordered breathing. 4, Computer System

[0300] FIG. 24 depicts an example system that may execute techniques presented herein. FIG. 24 is a simplified functional block diagram of a computer that may be configured to execute techniques described herein, according to exemplary cases of the present disclosure. Specifically, the computer (or “platform” as it may not be a single physical computer infrastructure) may include a data communication interface 2460 for packet data communication. The platform may also include a central processing unit (“CPU”) 2420, in the form of one or more processors, for executing program instructions. The platform may include an internal communication bus 2410, and the platform may also include a program storage and/or a data storage for various data files to be processed and/or communicated by the platform such as ROM 2430 and RAM 2440, although the system 2400 may receive programming and data via network communications. The system 2400 also may include input and output ports 2450 to connect with input and output devices such as keyboards, mice, touchscreens, monitors, displays, etc. Of course, the various system functions may be implemented in a distributed fashion on a number of similar platforms, to distribute the processing load. Alternatively, the systems may be implemented by appropriate programming of one computer hardware platform.

[0301] The general discussion of this disclosure provides a brief, general description of a suitable computing environment in which the present disclosure may be implemented. In some cases, any of the disclosed systems, methods, and/or graphical user interfaces may be executed by or implemented by a computing system consistent with or similar to that depicted and/or explained in this disclosure. Although not required, aspects of the present disclosure are described in the context of computer-executable instructions, such as routines executed by a data processing device, e.g., a server computer, wireless device, and/or personal computer. Those skilled in the relevant art will appreciate that aspects of the present disclosure can be practiced with other communications, data processing, or computer system configurations, including: Internet appliances, hand-held devices (including personal digital assistants (“PDAs”)), wearable computers, all manner of cellular or mobile phones (including Voice over IP (“VoIP”) phones), dumb terminals, media players, gaming devices, virtual reality devices, multi-processor systems, microprocessor-based or programmable consumer electronics, set-top boxes, network PCs, minicomputers, mainframe computers, and the like. Indeed, the terms “computer,” “server,” and the like, are generally used interchangeably herein, and refer to any of the above devices and systems, as well as any data processor.

[0302] Aspects of the present disclosure may be embodied in a special purpose computer and/or data processor that is specifically programmed, configured, and/or constructed to perform one or more of the computer-executable instructions explained in detail herein. While aspects of the present disclosure, such as certain functions, are described as being performed exclusively on a single device, the present disclosure may also be practiced in distributed environments where functions or modules are shared among disparate processing devices, which are linked through a communications network, such as a Local Area Network (“LAN”), Wide Area Network (“WAN”), and/or the Internet. Similarly, techniques presented herein as involving multiple devices may be implemented in a single device. In a distributed computing environment, program modules may be located in both local and/or remote memory storage devices.

[0303] Aspects of the present disclosure may be stored and/or distributed on non-transitory computer- readable media, including magnetically or optically readable computer discs, hard-wired or preprogrammed chips (e.g., EEPROM semiconductor chips), nanotechnology memory, biological memory, or other data storage media. Alternatively, computer implemented instructions, data structures, screen displays, and other data under aspects of the present disclosure may be distributed over the Internet and/or over other networks (including wireless networks), on a propagated signal on a propagation medium (e.g., an electromagnetic wave(s), a sound wave, etc.) over a period of time, and/or they may be provided on any analog or digital network (packet switched, circuit switched, or other scheme).

[0304] Program aspects of the technology may be thought of as “products” or “articles of manufacture” typically in the form of executable code and/or associated data that is carried on or embodied in a type of machine-readable medium. “Storage” type media include any or all of the tangible memory of the computers, processors or the like, or associated modules thereof, such as various semiconductor memories, tape drives, disk drives and the like, which may provide non-transitory storage at any time for the software programming. All or portions of the software may at times be communicated through the Internet or various other telecommunication networks. Such communications, for example, may enable loading of the software from one computer or processor into another, for example, from a management server or host computer of the mobile communication network into the computer platform of a server and/or from a server to the mobile device. Thus, another type of media that may bear the software elements includes optical, electrical and electromagnetic waves, such as used across physical interfaces between local devices, through wired and optical landline networks and over various air-links. The physical elements that carry such waves, such as wired or wireless links, optical links, or the like, also may be considered as media bearing the software. As used herein, unless restricted to non-transitory, tangible “storage” media, terms such as computer or machine “readable medium” refer to any medium that participates in providing instructions to a processor for execution.

5, Terminology

[0305] The terminology used above may be interpreted in its broadest reasonable manner, even though it is being used in conjunction with a detailed description of certain specific examples of the present disclosure. Indeed, certain terms may even be emphasized above; however, any terminology intended to be interpreted in any restricted manner will be overtly and specifically defined as such in this Detailed Description section. Both the foregoing general description and the detailed description are exemplary and explanatory only and are not restrictive of the features, as claimed.

[0306] As used herein, the terms “comprises,” “comprising,” “having,” including,” or other variations thereof, are intended to cover a non-exclusive inclusion such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements, but may include other elements not expressly listed or inherent to such a process, method, article, or apparatus.

[0307] In this disclosure, relative terms, such as, for example, “about,” “substantially,” “generally,” and “approximately” are used to indicate a possible variation of ±10% in a stated value.

[0308] The term “exemplary” is used in the sense of “example” rather than “ideal.” As used herein, the singular forms “a,” “an,” and “the” include plural reference unless the context dictates otherwise.

6, Examples

[0309] Exemplary embodiments of the systems and methods disclosed herein are described in the numbered paragraphs below.

[0310] Al. A method for maintaining upper airway patency, the method comprising :

[0311] placing, for a patient, at least one electrode into electrical communication with a target site of a palatal muscle, a pharyngeal muscle, and/or a nerve that innervates the palatal muscle and/or the pharyngeal muscle; and

[0312] activating the at least one electrode to deliver an electrical signal to the target site.

[0313] A2. The method of Al, wherein the target site is selected to target one or combinations of: a tensor veli palatini muscle, a levator veli palatini muscle, a palatopharyngeus muscle, a palatoglossus muscle, a musculus uvulae muscle, a superior constrictor muscle, and/or a middle constrictor muscle.

[0314] A3. The method of any of A1-A2, wherein the target site selected to target one or combinations of: (a) a branch of a maxillary division of a trigeminal nerve that innervates a levator veli palatini muscle including a lesser palatine nerve, a palatopharyngeus muscle including the lesser palatine nerve, a palatoglossus muscle including the lesser palatine nerve, a musculus uvulae muscle including the lesser palatine nerve; (b) a branch of a mandibular division of the trigeminal nerve that innervates a tensor veli palatini muscle including a nerve to tensor veli palatini; and (c) a branch of a pharyngeal plexus that innervates a superior constrictor muscle including a pharyngeal plexus branch to the superior constrictor muscle; and/or a nerve to the superior constrictor muscle.

[0315] A4. The method of A3, further comprising delivering the electrical signal to the target site, and the target site is selected to target one or combinations of: the tensor veli palatini muscle of the patient, the superior constrictor muscle of the patient, and/or a middle constrictor muscle of the patient. [0316] A5. The method of any of A 1 -A4, wherein the target site is selected to target one or combinations of: a nerve that innervates a levator veli palatini muscle, a palatopharyngeus muscle, a palatoglossus muscle, a musculus uvulae muscle, a tensor veli palatini muscle, and/or a superior constrictor muscle.

[0317] A6. The method of any of A1-A5, wherein activating the at least one electrode to deliver the electrical signal to the target site includes: stimulating motor neurons of one or combinations of: (a) a maxillary branch of a trigeminal nerve that innervates a levator veli palatini muscle, a palatoglossus muscle, a palatopharyngeus muscle, a musculus uvulae muscle including motor neurons of a lesser palatine nerve; (b) a mandibular branch of the trigeminal nerve that innervates a tensor veli palatini muscle including motor neurons of a nerve to tensor veli palatini; and/or (c) a branch of a pharyngeal plexus that innervates a superior constrictor muscle including motor neurons of a nerve to superior constrictor muscle.

[0318] A7. The method of any of A1-A6, wherein the target site is a muscle that is the palatal muscle and/or the pharyngeal muscle, including one or combinations of: a tensor veli palatini muscle, a levator veli palatini muscle, a palatopharyngeus muscle, a palatoglossus muscle, a musculus uvulae muscle, a superior constrictor muscle, and/or a middle constrictor muscle.

[0319] A8. The method of any of A1-A7, wherein activating the at least one electrode to deliver the electrical signal to the target site of the palatal muscle and/the or pharyngeal muscle includes stimulating motor fibres to cause partial or full, or tetanic or sub-tetanic contraction of the palatal muscle and/or the pharyngeal muscle including contraction of one or combinations of: a tensor veli palatini muscle, a levator veli palatini muscle, a palatopharyngeus muscle, a palatoglossus muscle, a musculus uvulae muscle, a superior constrictor muscle, and/or a middle constrictor muscle.

[0320] A9. The method of any of A1-A8, wherein the target site is one of a plurality of target sites of nerves or muscles that are in communication with one or more palatal muscles and/or pharyngeal muscles, and the plurality of target sites are selected to target a set including one or combinations of: a tensor veli palatini muscle, a levator veli palatini muscle, a palatopharyngeus muscle, a palatoglossus muscle, a musculus uvulae muscle, a superior constrictor muscle, and/or a middle constrictor muscle.

[0321] A10. The method of any of A1-A9, further comprising delivering the electrical signal to the target site of one or combinations of: a hypoglossal nerve, an ansa cervicalis nerve, a branch of a pharyngeal plexus to a palatopharyngeus muscle, a branch of the pharyngeal plexus to a palatoglossus muscle, a branch of the pharyngeal plexus to a middle constrictor muscle, a longitudinal tongue muscle, a transverse tongue muscle, a vertical tongue muscle, a genioglossus muscle, a hyoglossus muscle, and/or a styloglossus muscle.

[0322] Bl. A delivery system placed internally in an oral cavity, nasal cavity, oropharynx, and/or nasopharynx, the delivery system comprising:

[0323] at least one electrode configured to deliver an electrical signal to a target site that is a nerve or muscle;

[0324] a power source in wired or wireless communication with the at least one electrode; and [0325] a controller in communication with the at least one electrode and programmed to direct delivery of the electrical signal by the at least one electrode to the target site.

[0326] B2. The delivery system of B 1, wherein application of the delivery system is used to improve upper airway patency.

[0327] B3. The delivery system of any of B1-B2, wherein the electrical signal comprises of successive pulse trains.

[0328] B4. The delivery system of any of B 1-B3, wherein delivery of the electrical signal comprises of placing at least one electrode into electrical communication with the target site of the nerve or the muscle through one or combinations of: an oral approach, and/or a nasal approach. [0329] B5. The delivery system of any of B 1 -B4, wherein the controller and the power source are enclosed within an oral and/or nasal appliance in wireless and/or wired communication with the at least one electrode.

[0330] B6. The delivery system of any of B 1-B5, wherein the at least one electrode is a submucosally implanted electrode in wireless and/or wired communication with the controller and the power source. [0331] B7. The delivery system of any of B 1-B6, wherein the at least one electrode is an enclosed electrode within an oral and/or nasal appliance placed in wired and/or wireless communication with the controller and the power source.

[0332] B8. The delivery system of any of B 1-B7, wherein delivery of the electrical signal by the at least one electrode to the target site is initiated by removing the delivery system from a charging system and/or pressing an activation button with a timer.

[0333] B9. The delivery system of any of B 1-B8, wherein delivery of the electrical signal by the at least one electrode to the target site is initiated by one or combinations of: optical sensing of device placement, proprioceptive sensing of device placement, mechanical sensing of device placement, moisture sensing, chemical sensing, physical patient orientation, stillness of body, and/or time of day.

[0334] B10. The delivery system of any of B 1-B9, further comprising of a sensor in wired and/or wireless communication with the at least one electrode, the sensor is configured to sense a physiological and/or anatomical parameter and generate a sensor signal based on the physiological and/or anatomical parameter, the controller in wired and/or wireless communication with the sensor, the controller is programmed to direct delivery of the electrical signal to the target site by the at least one electrode based on the sensor signal.

[0335] Bl l. The delivery system of BIO, wherein the physiological and/or anatomical parameter that is being sensed by the sensor is associated with sleep disordered breathing including one or combinations of: acoustic vibration, mechanical vibration, airflow parameters, blood flow parameters, heart rate, oxygen saturation, muscle activity, and/or nerve activity.

[0336] B 12. The delivery system of B 10, wherein the sensor is located within or near to one or combinations of: airway, vasculature, musculature, nerve pathways, and/or mucosa.

[0337] B 13. The delivery system of B 10, wherein the controller includes software configured to analyze the sensor signal.

[0338] Other aspects of the disclosure will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the invention being indicated by the following claims.

Claims

Claims What is claimed is:

1. A method for maintaining upper airway patency, the method comprising: placing, for a patient, at least one electrode into electrical communication with a target site of a palatal muscle, a pharyngeal muscle, and/or a nerve that innervates the palatal muscle and/or the pharyngeal muscle; and activating the at least one electrode to deliver an electrical signal to the target site.

2. The method of claim 1, wherein the target site is selected to target one or combinations of: a tensor veli palatini muscle, a levator veli palatini muscle, a palatopharyngeus muscle, a palatoglossus muscle, a musculus uvulae muscle, a superior constrictor muscle, and/or a middle constrictor muscle.

3. The method of claim 1, wherein the target site selected to target one or combinations of: (a) a branch of a maxillary division of a trigeminal nerve that innervates a levator veli palatini muscle including a lesser palatine nerve, a palatopharyngeus muscle including the lesser palatine nerve, a palatoglossus muscle including the lesser palatine nerve, a musculus uvulae muscle including the lesser palatine nerve; (b) a branch of a mandibular division of the trigeminal nerve that innervates a tensor veli palatini muscle including a nerve to tensor veli palatini; and (c) a branch of a pharyngeal plexus that innervates a superior constrictor muscle including a pharyngeal plexus branch to the superior constrictor muscle; and/or a nerve to the superior constrictor muscle.

4. The method of claim 3, further comprising delivering the electrical signal to the target site, and the target site is selected to target one or combinations of: the tensor veli palatini muscle of the patient, the superior constrictor muscle of the patient, and/or a middle constrictor muscle of the patient.

5. The method of claim 1, wherein the target site is selected to target one or combinations of: a nerve that innervates a levator veli palatini muscle, a palatopharyngeus muscle, a palatoglossus muscle, a musculus uvulae muscle, a tensor veli palatini muscle, and/or a superior constrictor muscle.

6. The method of claim 1, wherein activating the at least one electrode to deliver the electrical signal to the target site includes : stimulating motor neurons of one or combinations of: (a) a maxillary branch of a trigeminal nerve that innervates a levator veli palatini muscle, a palatoglossus muscle, a palatopharyngeus muscle, a musculus uvulae muscle including motor neurons of a lesser palatine nerve; (b) a mandibular branch of the trigeminal nerve that innervates a tensor veli palatini muscle including motor neurons of a nerve to tensor veli palatini; and/or (c) a branch of a pharyngeal plexus that innervates a superior constrictor muscle including motor neurons of a nerve to superior constrictor muscle.

7. The method of claim 1, wherein the target site is a muscle that is the palatal muscle and/or the pharyngeal muscle, including one or combinations of: a tensor veli palatini muscle, a levator veli palatini muscle, a palatopharyngeus muscle, a palatoglossus muscle, a musculus uvulae muscle, a superior constrictor muscle, and/or a middle constrictor muscle.

8. The method of claim 1, wherein activating the at least one electrode to deliver the electrical signal to the target site of the palatal muscle and/the or pharyngeal muscle includes stimulating motor fibres to cause partial or full, or tetanic or sub-tetanic contraction of the palatal muscle and/or the pharyngeal muscle including contraction of one or combinations of: a tensor veli palatini muscle, a levator veli palatini muscle, a palatopharyngeus muscle, a palatoglossus muscle, a musculus uvulae muscle, a superior constrictor muscle, and/or a middle constrictor muscle.

9. The method of claim 1, wherein the target site is one of a plurality of target sites of nerves or muscles that are in communication with one or more palatal muscles and/or pharyngeal muscles, and the plurality of target sites are selected to target a set including one or combinations of: a tensor veli palatini muscle, a levator veli palatini muscle, a palatopharyngeus muscle, a palatoglossus muscle, a musculus uvulae muscle, a superior constrictor muscle, and/or a middle constrictor muscle.

10. The method of claim 1, further comprising delivering the electrical signal to the target site of one or combinations of: a hypoglossal nerve, an ansa cervicalis nerve, a branch of a pharyngeal plexus to a palatopharyngeus muscle, a branch of the pharyngeal plexus to a palatoglossus muscle, a branch of the pharyngeal plexus to a middle constrictor muscle, a longitudinal tongue muscle, a transverse tongue muscle, a vertical tongue muscle, a genioglossus muscle, a hyoglossus muscle, and/or a styloglossus muscle.

11. A delivery system placed internally in an oral cavity, nasal cavity, oropharynx, and/or nasopharynx, the delivery system comprising: at least one electrode configured to deliver an electrical signal to a target site that is a nerve or muscle; a power source in wired or wireless communication with the at least one electrode; and a controller in communication with the at least one electrode and programmed to direct delivery of the electrical signal by the at least one electrode to the target site.

12. The delivery system of claim 11, wherein application of the delivery system is used to improve upper airway patency.

13. The delivery system of claim 11, wherein the electrical signal comprises of successive pulse trains.

14. The delivery system of claim 11, wherein delivery of the electrical signal comprises of placing at least one electrode into electrical communication with the target site of the nerve or the muscle through one or combinations of: an oral approach, and/or a nasal approach.

15. The delivery system of claim 11, wherein the controller and the power source are enclosed within an oral and/or nasal appliance in wireless and/or wired communication with the at least one electrode.

16. The delivery system of claim 11, wherein the at least one electrode is a submucosally implanted electrode in wireless and/or wired communication with the controller and the power source.

17. The delivery system of claim 11, wherein the at least one electrode is an enclosed electrode within an oral and/or nasal appliance placed in wired and/or wireless communication with the controller and the power source.

18. The delivery system of claim 11, wherein delivery of the electrical signal by the at least one electrode to the target site is initiated by removing the delivery system from a charging system and/or pressing an activation button with a timer.

19. The delivery system of claim 11, wherein delivery of the electrical signal by the at least one electrode to the target site is initiated by one or combinations of: optical sensing of device placement, proprioceptive sensing of device placement, mechanical sensing of device placement, moisture sensing, chemical sensing, physical patient orientation, stillness of body, and/or time of day.

20. The delivery system of claim 11, further comprising of a sensor in wired and/or wireless communication with the at least one electrode, the sensor is configured to sense a physiological and/or anatomical parameter and generate a sensor signal based on the physiological and/or anatomical parameter, the controller in wired and/or wireless communication with the sensor, the controller is programmed to direct delivery of the electrical signal to the target site by the at least one electrode based on the sensor signal.

21. The delivery system of claim 20, wherein the physiological and/or anatomical parameter that is being sensed by the sensor is associated with sleep disordered breathing including one or combinations of: acoustic vibration, mechanical vibration, airflow parameters, blood flow parameters, heart rate, oxygen saturation, muscle activity, and/or nerve activity.

22. The delivery system of claim 20, wherein the sensor is located within or near to one or combinations of: airway, vasculature, musculature, nerve pathways, and/or mucosa.

23. The delivery system of claim 20, wherein the controller includes software configured to analyze the sensor signal.