WO2025199246A1 - Systems and methods for controlling e-field intensity for a scalp region and a brain region using a multichannel tms coil array - Google Patents

Abstract

A method for controlling E-field intensity for a scalp region and a target brain region of a subject using a multichannel transcranial magnetic stimulation (TMS) coil array having a plurality of TMS coils and a plurality of coil elements includes calculating an electric field (E- field) for each coil element in the mTMS coil array and combining the E-field of two or more coil elements to create a predetermined E-field intensity for the scalp region and a predetermined E-field intensity for the target brain region. The method further includes determining an electrical signal for each coil element based on the calculated E-field corresponding to each coil element, applying the electrical signals determined for the two or more coil elements with combined E-fields simultaneously to the two or more coil elements, and applying the electrical signals determined for each coil element without combined E-fields to the corresponding coil element.

Description

SYSTEMS AND METHODS FOR CONTROLLING E-FIELD INTENSITY FORA SCALP REGION AND A BRAIN REGION USING A MULTICHANNEL TMS COIL ARRAY

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is based on, claims priority to, and incorporates herein by reference in its entirety U.S. Serial No. 63/567,362 fded March 19, 2024, and entitled “Multi-Coil System to Mitigate Muscle and Nerve Activation for Transcranial Magnetic Stimulation."

FIELD

[0002] The present disclosure relates generally to transcranial magnetic stimulation (TMS) and, more particularly, to systems and methods for controlling E-field intensity for a scalp region and a target brain region of a subject using a multichannel transcranial magnetic stimulation (TMS) coil array.

BACKGROUND

[0003] Transcranial magnetic stimulation (TMS) is a noninvasive neuromodulation technique used for basic neuroscience and clinical applications, including diagnostic (e.g., motor system biomarkers, pre-surgical mapping) and therapeutic (e.g., major depression disorder, obsessive compulsive disorder, migraines). TMS uses magnetic fields to stimulate nerve cells in the brain of the subject. The magnetic fields are generated by an electromagnetic coil that is placed over the scalp of the subject to induce electric currents in the underlying brain tissue. The magnetic fields are generated by electric pulses applied to and flowing though the electromagnetic coil. The magnetic fields pass through the skull and into the brain. The position of the coil over the scalp of the subject can be selected to focus on and target a specific area or site of the brain for stimulation. The target region of the brain can be determined by the structure or function of the brain estimated using neuroimaging techniques such as anatomical or functional magnetic resonance imaging (MRI/fMRI). The brain target is typically selected on the surface of the brain. The goal of TMS is to generate sufficiently strong electromagnetic fields in a specific region of the brain of the patient to stimulate the appropriate brain network based on the diagnostic or therapeutic application. It is desirable to place the TMS coil in a selected position so that, for example, the target region in the brain has the strongest possible electric field.

[0004] TMS can be employed to stimulate the human brain with clearly suprathreshold intensities. However, based on physical principles of low frequency electromagnetic fields, the maximum of the stimulating electric field (E-field) is always closest to the coil and results in an activation of scalp and sensory nerves that lie between the brain and the coil. This is problematic in several ways as muscle and nerve activation may cause discomfort to the subject and it can also confound concurrent recording of electrical or hemodynamic measurements of brain activity using for instance electroencephalography (EEG) or functional MRI (fMRI). For example, muscle and nerve activation can cause artifacts in EEG and fMRI measurements. Current solutions to reduce muscle artifacts include, for example, changing the coil location and orientation, reducing the TMS intensity, using smaller and more focal coils, and offline artifact removal techniques.

SUMMARY

[0005] In accordance with an embodiment, a method for controlling E-field intensity for a scalp region and a target brain region of a subject using a multichannel transcranial magnetic stimulation (TMS) coil array having a plurality of TMS coils and a plurality of coil elements includes calculating, using a processor device, an electric field (E-field) for each coil element in the mTMS coil array, combining, using the processor device, the E-field of two or more coil elements to create a predetermined E-field intensity for the scalp region and a predetermined E- field intensity for the target brain region, determining, using the processor device, an electrical signal for each coil element based on the calculated E-field corresponding to each coil element, applying, using a signal generator, the electrical signals determined for the two or more coil elements with combined E-fields simultaneously to the two or more coil elements, and applying, using the signal generator, the electrical signals determined for each coil element without combined E-fields to the corresponding coil element.

[0006] In accordance with another embodiment, a system for controlling E-field intensity for a scalp region and a target brain region of a subject using a multichannel transcranial magnetic stimulation (TMS) coil array having a plurality of TMS coils and a plurality of coil elements includes a memory that stores one or more computer readable media that includes instructions and one or more processor devices configured to execute the instructions of the computer readable media to calculate an electric field (E-field) for each coil element in the mTMS coil array, combine the E-field of two or more coil elements to create a predetermined E-field intensity for the scalp region and a predetermined E-field intensity for the target brain region, determine an electrical signal for each coil element based on the calculated E-field corresponding to each coil element, apply the electrical signals determined for the two or more coil elements with combined E-fields simultaneously to the two or more coil elements, and apply the electrical signals determined for each coil element without combined E-fields to the corresponding coil element.

BRIEF DESCRIPTION OF THE DRAWINGS

[0007] The present disclosure will hereafter be described with reference to the accompanying drawings, wherein like reference numerals denote like elements.

[0008] FIG. l is a block diagram of an example transcranial magnetic stimulation (TMS) system in accordance with an embodiment;

[0009] FIGs. 2A and 2B are perspective views of an example multichannel TMS (mTMS) coil array in accordance with an embodiment;

[0010] FIG. 3 is a perspective view of an example multichannel TMS (mTMS) coil array in accordance with an embodiment;

[0011] FIG. 4 is a perspective view of an example 3-axis TMS coil in accordance with an embodiment;

[0012] FIG. 5 illustrates a method for controlling E-field intensity for a scalp region and a target brain region of a subject using a multichannel transcranial magnetic stimulation (TMS) coil array in accordance with an embodiment;

[0013] FIG. 6 is a block diagram of an example computer system in accordance with an embodiment;

[0014] FIG. 7 is a block diagram of an example electroencephalography system in accordance with an embodiment; and

[0015] FIG. 8 is a block diagram of an example magnetic resonance imaging (MRI) system in accordance with an embodiment. DETAILED DESCRIPTION

[0016] FIG. 1 is a block diagram of an example transcranial magnetic stimulation (TMS) system in accordance with an embodiment. A TMS system 100 may include an input 102, a controller 104, a signal generator 106 (e.g., a signal stimulator) and an electromagnetic coil 108. The controller 104 is in communication with the signal generator 106 and is configured to direct the signal generator 106 to provide various signals to the electromagnetic coil 108. In some implementations, the controller 104 may be any general-purpose computing system or device, such as a personal computer, workstation, cellular phone, smartphone, laptop, tablet, or the like. As such, the controller 104 may include any suitable hardware and components designed or capable of carrying out a variety of processing and control tasks, including steps for optimizing and directing the signal generator 106 to provide various signals to the electromagnetic coil 108. For example, the controller 104 may include a programmable processor or combination of programmable processors, such as central processing units (CPUs), graphics processing units (GPUs), and the like. In some implementations, the controller 104 may be configured to execute instructions stored in a non-transitory computer readable-media. In this regard, the controller 104 may be any device or system designed to integrate a variety of software, hardware, capabilities and functionalities. Alternatively, and by way of particular configurations and programming, the controller 104 may be a special -purpose system or device. For instance, such special-purpose system or device may include one or more dedicated processing units or modules that may be configured (e.g., hardwired, or pre-programmed) to carry out steps, in accordance with aspects of the present disclosure.

[0017] The electromagnetic coil 108 is positioned proximate to and over the head, for example, the scalp 118, of a subject 112. In some embodiments, the electromagnetic coil 108 can include a plurality of TMS coils arranged in a TMS coil array such as a multichannel TMS (mTMS) array as described further below with respect to FIGs. 2A, 2B, 3 and 4 below. The electromagnetic coil 108 may be insulated using known methods and materials. In some embodiments, the electromagnetic coil 108 may be positioned and held in place over the scalp 118 by an operator or using a mechanical arm (not shown). The position of the coil 108 over the scalp 118 is selected to target and stimulate a specific area of the brain (e.g., a region, site or target in the brain). Accordingly, the electromagnetic coil 108 may be positioned over the region to be stimulated in the brain. Signal generator 106 can be configured to generate and deliver electrical signals (e.g., electric current or voltage signals) to the electromagnetic coil 108. In some embodiments, the signal generator 106 may be based on capacitor banks, power amplifiers, or H- bridge type designs. The electric current delivered from the signal generator 106 and flowing through the electromagnetic coil 108 generates a magnetic field 114. The magnetic field 114 (e.g., magnetic pulses) passes through the skull 110 and into the brain 120 of the subject 112 and cause or induce electrical currents 116 that stimulate nerve cells in the targeted brain region. Different coil types may be used for electromagnetic coil 108 to elicit different magnetic field patterns. The strength and distribution of the time-varying magnetic fields 114 may be dependent on both the geometry and the amount of current traveling through the electromagnetic coil 108. The induced electric field 114 may also be dependent on fixed variables unique to individual subjects such as the geometry and electrical properties of anatomies in and around the brain. The induced electric field may also be triggered by the user or by the controller 104 based on external data such as magnetic resonance imaging (MRI) data, functional MRI (fMRI) data, electroencephalography (EEG) data, or the like.

[0018] In some embodiments, the signals generated by the signal generator 106 and provided to the electromagnetic coil 108 may be in the form of a pulse sequence having a plurality of pulses. The power, amplitude, duration, shape, and frequency of the pulses may be selected to achieve a desired level of or depth of stimulation, as well as to optimize heat or magnetic forces induced in the electromagnetic coil 108. An operator may select the specific type and characteristics of the electric pulses to be generated by the signal generator 106 using an input 102 coupled to the controller 104. The input 102 can be, for example, a keyboard, a mouse, a touch screen, etc. [0019] As mentioned above, the TMS system 100 can include a TMS coil array having a plurality of TMS coils such as a multichannel TMS (mTMS) array. FIGs. 2A and 2B are perspective views of an example multichannel TMS (mTMS) coil array in accordance with an embodiment. Multichannel TMS coil arrays can be configured to enable multiple sites to be stimulated simultaneously or sequentially under electronic control (e.g., controller 104 and signal generator 106 shown in FIG. 1) without moving the TMS coils. In FIG. 2A, an mTMS coil array 202 is shown that includes a first TMS coil 204 and a second TMS coil 206. FIG. 2B illustrates the two coil mTMS coil array 202 positioned on a subject’s head. As discussed above, the mTMS coil array 202 may be positioned and held in place over the scalp of the subject 208 by an operator (not shown) or using a mechanical arm (not shown). [0020] While a two coil mTMS coil array 202 is illustrated in FIGs. 2A and 2B, in some embodiments an mTMS coil array may include any number of TMS coils, for example, 4 TMS coils, 16 TMS coils, n TMS coils, etc. FIG. 3 is a perspective view of an example multichannel TMS (mTMS) coil array in accordance with an embodiment. The mTMS coil array 302 in FIG. 3 is a four coil array and includes a first TMS coil 304, a second TMS coil 306, a third TMS coil 310 and a fourth TMS coil 312. In FIG. 3, the four coil mTMS coil array 302 is illustrated positioned on a subject’s head. As discussed above, the mTMS coil array 302 may be positioned and held in place over the scalp of the subject 308 by an operator (not shown) or using a mechanical arm (not shown).

[0021] In some embodiments, each TMS coil (e.g., coils 204 and 206 in FIG 2A and coils 304, 306, 310, 312 in FIG. 3) in an mTMS coil array can include a single coil element (e.g., a circular coil element. In some embodiments, each TMS coil (e.g., coils 204 and 206 in FIG 2A and coils 304, 306, 310, 312 in FIG. 3) in an mTMS coil array can include a plurality of coils elements, for example, a 3-axis TMS coil. FIG. 4 is a perspective view of an example 3-axis TMS coil in accordance with an embodiment. In FIG. 4, a 3-axis TMs coil 402 includes three orthogonal separate solenoid elements: 1) an x-element 404; 2) a y-element 406; and 3) a z-element 408. Each of the three coil elements, x-element 404, y-element 406, z-element 408, can be, for example, a circular coil element. In the embodiment illustrated in FIG. 4, the z-element 408 can be oriented parallel to the scalp surface and combined with the x-element 404 and the y-element 406 that can be wound on a spherically symmetric coil form in an interleaved fashion (e.g., with interleaved windings). The x-element 404 and y-element 406 advantageously add degrees of freedom to the overall field shaping capabilities of an mTMS coil array (e.g., mTMS coil array shown in FIG. 2A and mTMS coil array 302 shown in FIG. 3). In some embodiments, the winding pattern of the z-element 408 can be designed to allow positioning of the x-element 404 and the y-element 406 as close to the bottom of the entire 3-axis TMS coil assembly 402 as possible. A 3-axis TMS coil 402 can, for example, advantageously provide simple and effective decoupling between the elements 404, 406, 408, offer a compact footprint that can be used to increase the degrees of freedom (e.g., number of elements), and permit conformal positioning of each individual TMS coil in the mTMS coil array tangential to the scalp for available head sizes. In some embodiments, each coil element 404, 406, 408 in the 3-axis TMS coil can be independently activated (e.g., using controller 104 and signal generator 106 shown in FIG. 1) to, for example, enable simultaneous and sequential stimulation of multiple areas or regions of the brain.

[0022] TMS can be used in both clinical and research settings. As mentioned above, TMS can be used in the clinical setting for diagnostic (e.g., motor system biomarkers, pre-surgical mapping) and therapeutic (e.g., major depression disorder, obsessive compulsive disorder, migraines) applications. In some embodiments, TMS can be performed concurrently with EEG measurements of brain activity. In some embodiments, a TMS-EEG system may be a closed- loop system. Electroencephalography (EEG) is a non-invasive neurophysiological technique, which measures signals that reflect the summation of postsynaptic potentials of relatively large groups of neurons firing synchronously. This synchronous activity can be monitored with millisecond temporal resolution allowing accurate tracking of the rapidly changing electrical dynamics of neuronal populations. In some embodiments, in a TMS-EEG system, EEG electrodes or sensors (e.g., EEG electrodes 702 shown in FIG. 7) can be coupled to the subject’s scalp and a TMS coil or TMS coil array can be positioned proximate to and over the scalp and EEG electrodes. In some embodiments, TMS can be performed concurrently with functional magnetic resonance imaging (fMRI). In some embodiments, a TMS-fMRI system may be a closed-loop system. fMRI is a widely used method for non-invasive mapping of brain activity. It reveals the whole-brain hemodynamic response to tasks or stimuli with millimeter spatial resolution based on the BOLD effect. fMRI provides an indirect measure of neuronal activity that is characterized by the underlying neurovascular coupling mechanism. When integrating fMRI with TMS, the RF coil arrays used for fMRI acquisition and the TMS coils must both be placed in close proximity of the head. In an example, a TMS coil or TMS coil array may be positioned proximate to and over the scalp of the subject and within a bore of an MRI system (e.g., MRI system 800 described below with respect to FIG. 8). In an example of concurrent TMS-fMRI, TMS pulses can be delivered to a target brain region in between volume acquisition in an echo planar imaging (EPI) time series, which enables a depiction of blood-oxygen level dependent changes caused by the TMS stimulus. As mentioned, muscle and nerve activation in the scalp caused by the stimulating E-fields during TMS can cause artifacts in EEG or fMRI measurements acquired concurrently with the TMS.

[0023] In the research setting, studies, e.g., clinical trials, can be performed to evaluate the efficacy and safety of TMS techniques and protocols for various applications. The TMS coil or TMS coil array can be controlled to generate different stimulation conditions, for example, active TMS or sham TMS. As discussed above, active TMS involves using a TMS coil or a TMS coil array to apply magnetic field to stimulate the brain (e.g., one or more target regions) and induce electric fields in the target region(s). Sham TMS reduces stimulation so there is no activation of brain regions (or no suprathreshold response) or eliminates stimulation of the brain. Sham TMS is a crucial component of TMS studies as it can be used to isolate neural effects by controlling “placebo” responses, minimize sensory confounds, ensure blinding integrity, and assure that observed effects are genuinely due to the stimulation itself rather than psychological or other non-specific factors. Commonly, it can be desirable to perform double blind (i.e., where neither the participants nor the researchers know which treatment (active TMS or sham TMS) is being administered). Current sham TMS methods include, for example, coil tilting or displacement, inactive coil systems that have electrodes to mimic sensory stimuli, active-sham pulse integration and spacing the TMS coil from the scalp. However, existing sham TMS techniques present challenges such as difficulty in accurately replicating the sensory experience of real TMS, lack of controlling brain activation versus scalp activation, and maintaining double-blinding in longterm studies. Additionally, the effectiveness of sham TMS can vary by target region and stimulation intensity, leading to inconsistencies in control conditions across studies.

[0024] The present disclosure describes systems and methods for controlling E-field intensity for a scalp region and a target brain region of a subject using a multichannel TMS (mTMS) coil array. In some embodiments, the E-field intensity for the scalp region and the E-field intensity for the target brain region can be controlled by calculating an E-field for each coil element in the mTMS coil array and combining the E-fields of different coil elements. In some embodiments, the calculated E-fields of different coil elements in the mTMS coil can be combined to maximize the E-field intensity in the target brain region and to minimize the E-field intensity in the scalp region. In some embodiments, during TMS activation, the coil elements in a set of coil elements with combined E-fields can be activated simultaneously. Accordingly, an mTMS coil array can be used to mitigate scalp artifacts (e.g., caused by muscle and nerve activation in the scalp region) in EEG and fMRI measurements by the minimization of the E-field in the scalp region. In addition, reduced scalp activation can significantly increase the comfort of the subject during therapeutic and diagnostic TMS applications. In some embodiments, the calculated E-fields of different coil elements in the mTMS coil can be combined to maximize the E-field intensity in the scalp region and minimize the E-field intensity in the target brain region. Accordingly, an mTMS coil array can be used to control the E-field intensity in the scalp region and the E-field intensity in the target brain region to generate sham conditions where the muscles and nerves in the scalp may be activated by the E-field intensity in the scalp region to provide similar sensation as with active TMS (or real TMS) while the reduced E-field intensity in the target brain region can be configured to minimize the effect on the target brain region (e.g., preventing activation of the target brain region). Advantageously, the disclosed systems and methods can be used to generate any combination of scalp E-field intensity and brain E-field intensity (or degrees of stimulation), for example, different sham conditions (or blinding levels), and enables adjustment of the E-field intensities to different scalp/brain E-field intensity combinations (also referred to herein as continuously adjustable sham (CASh) TMS system).

[0025] FIG. 5 illustrates a method for controlling E-field intensity for a scalp region and a target brain region of a subject using a multichannel transcranial magnetic stimulation (TMS) coil array in accordance with an embodiment. Although the blocks of the process are illustrated in a particular order, in some embodiments, one or more blocks may be executed in a different order than illustrated in FIG. 5 or may be bypassed. One or more aspects of the method may be performed by a processing system including at least one electronic processor, where the at least one electronic processor may be or include a processor as described herein. One or more aspects of the method may be performed using a signal generator (or signal stimulator) in communication with the processing system.

[0026] At block 502, an E-field for each coil element in an mTMS coil array of a TMS system (e.g., TMS system 100 shown in FIG. 1, electromagnetic coil 108 shown in FIG. 1, TMS coils arrays 202, 302 shown in FIGs. 2A and 3) can be calculated. For example, for a TMS coil array with two TMS coils where each coil has a single element, an E-field can be calculated for each of the two coil elements (e.g., one in each coil). In another example, for a TMS coil array with two TMS coils where each coil has three coil elements (e.g., a 3-axis TMS coil 402 shown in FIG. 4), an E-field can be calculated for each of the twelve coil elements (e.g., three in each coil). In some embodiments, the E-field of each coil is calculated for a brain region of interest (ROI), a scalp ROI, a brain region of avoidance (ROA), and a scalp ROA. The E-fields generated by each transcranial TMS element in an mTMS array can be computed using various methods, each tailored to account for the complex electromagnetic interactions within the system. Generally, the E-field at a given point in the brain is derived from the time-varying magnetic fields produced by the TMS coils, following Maxwell’s equations including Faraday’s law of induction. Finite element methods (FEM) can provide a numerical approach by simulating coil geometry, tissue conductivity, and boundary conditions to yield subject-specific E-field distributions. Additionally, the boundary element method accelerated by the fast multipole method (BEM-FMM) can offer an efficient alternative for solving large-scale bioelectromagnetic problems, significantly reducing computational complexity while maintaining accuracy. For multi-element arrays, superposition principles can be applied, where individual coil E-fields are computed separately and then combined to account for constructive and destructive interference. Analytical and computational models, including the quasi-static approximation of Maxwell’s equations, can be used to further refine predictions, optimizing stimulation parameters for precise neuromodulation.

[0027] At block 504, the calculated E-fields of at least two different coil elements can be combined to create a predetermined E-field intensity for a scalp region of the subject and a predetermined E-field intensity for a target brain region of the subject. In some embodiments, there can be a plurality of sets of two or more coil elements where in each set the E-field of the coil elements can be combined. In some embodiments, the E-fields of two or more coil elements can be combined by applying an optimization technique to create the predetermined E-field intensity for the scalp region and the predetermined E-field for the target brain region. For example, in some embodiments, a cost function and/or a target E-field pattern can be defined that is configured to encourage stronger combined E-fields at the brain and/or scalp ROIs while resulting in smaller E-fields at the brain and/or scalp RO As using all available coil elements. In some embodiments, the optimization technique may be stochastic or deterministic depending on the type of cost function (e.g., non-convex versus convex) that will result in the current rate-of- change amplitudes for all available coil elements that will result in the best possible “match” of the target E-field pattern. In some embodiments, the combination of E-fields for two or more coil elements can be performed empirically by measuring electromyographic or electroencephalographic signals from the scalp under the mTMS coil array and varying the E- field patterns on the scalp while keeping the E-field intensity in the target brain region fixed. [0028] In an example, the predetermined E-field intensity for the scalp region can be a minimized E-field intensity (e.g., to mitigate scalp artifacts during active TMS) and the predetermined E-field intensity can be a maximized E-field intensity or an E-field intensity that will provide a suprathreshold response in the target region of the brain. Accordingly, the E-field intensity for the scalp region and the E-field intensity for the target brain region can be controlled to mitigate scalp artifacts (e.g., to reduce or cancel the muscle and nerve activation in the scalp) and increase patient comfort. In another example, the predetermined E-field intensity in the scalp region can be a maximized E-field intensity and the predetermined E-field in the target brain region can be a minimized E-field intensity or an E-field intensity that will not provide a subthreshold response in the target region of the brain. Accordingly, the E-field intensity in the scalp region and the E-field intensity in the target brain region can be controlled using the mTMS coil array to provide sham TMS conditions. In some embodiments, the scalp and target brain region E-field intensity can be adjusted to different combinations of scalp and brain E-field intensities (e.g., different sham conditions or blinding levels) based on the combination of coil element E-fields to help make a subject more blind to different conditions. As mentioned above, the disclosed system and method advantageously enables the adjustment of the scalp E-field intensity and the target brain region E-field intensity to any combination of scalp and brain E- field intensity and provides a continuously adjustable sham (CASh) TMS system. The specific sham condition (or blinding level) used can be selected based on, for example, the stimulation protocol, task requirements, target brain region, and overall experimental consideration.

[0029] In some embodiments, the predetermined E-field intensity in the scalp region and the predetermine E-field intensity in the target brain region can be selected to produce a predetermined ratio (%). In some embodiments, the ratio can be a ratio of the E-field intensity on the scalp versus the E-field intensity in the brain, for example, as given by:

In some embodiments, the predetermined E-field intensity of the scalp region and the predetermined E-field intensity of the target brain region can be selected to reduce the ratio Rsb to, for example, reduce muscle artifacts during active TMS. In some embodiments, the ratio can be a ratio of the E-field intensity in the brain versus the E-field intensity on the scalp, for example, as given by:

R_a = ^E^Brain) _% (₂) In some embodiments, the predetermined E-field intensity of the scalp region and the predetermined E-filed intensity of the target brain region can be selected to create different sham conditions (or blinding levels).

[0030] At block 506, electrical signal or signals to be applied to each coil element in the mTMS coil array can be determined based on the calculated E-fields from block 502. As mentioned above, the E-field for each TMS element can be computed using established methods such as the finite element method (FEM) or the boundary element method accelerated by the fast multipole method (BEM-FMM). Once the E-field is calculated, its intensity can be modulated by adjusting a key parameter: the rate of change of current (dlldf). Since the induced E-field is directly proportional to dlldt, the required electrical signal (e.g., a current waveform) can be determined to achieve the desired stimulation intensity. The corresponding dlldt values can then be converted into maximum stimulator output (MSO) values, which represent the stimulator’s output intensity as a percentage of its maximum capacity. This conversion is based on a predefined relationship between dlldt and MSO, which can be derived through experimental calibration or computational modeling. The computed MSO values are then fed into the TMS stimulator (e.g., signal generator 106 shown in FIG. 1), which can precisely drive each TMS coil; element with the appropriate current waveform to achieve the desired E-field intensity.

[0031] At block 508, the determined electrical signals can be applied to each coil element including simultaneous application of the electrical signals to the two of more coil elements with combined E-fields. As mentioned above, in some embodiments, there can be a plurality of sets of two or more coil elements where in each set the E-field of the coil elements can be combined. In some embodiments, during TMS activation, the coil elements in a set of coil elements with combined E-fields can be activated simultaneously. As discussed above, by combining the E- fields of different coil elements and activating the coil elements simultaneously during TMS application, the E-field intensities of the scalp region and the E-field intensity of the target brain region can be adjusted to, for example, mitigate scalp artifacts or create sham TMS conditions. As discussed above with respect to FIG. 1, coil elements in an mTMS coil array can be activated (i.e., electrical signals applied to the coil element) using a controller 104 and a signal generator 106 of a TMS system 100.

[0032] In some embodiments, the systems and methods described herein can be used to create sham TMS conditions which can then be used to remove muscle artifacts from acquired EEG or fMRI measurements to determine the real brain response during the active TMS. The EEG or fMRI measurements can be acquired concurrently with TMS in, for example, a research study or a clinical application. In this embodiment, first an active TMS application is performed with concurrent EEG or fMRI measurements. Second, the mTMS coil array can be controlled to generate a sham TMS condition which is performed with concurrent EEG or fMRI measurements. The EEG or fMRI measurements from the sham TMS condition measure the noise generated by the TMS system such as, for example, scalp artifacts. In some embodiments, the EEG measurement acquired during the active TMS can be compared to the EEG measurements acquired during the sham TMS condition to identify the data representing the real brain response (e.g., the artifacts can be removed from the active TMS EEG measurement). In some embodiments, the fMRI measurements acquired during the active TMS can be compared to the fMRI measurements acquired during the sham TMS condition to identify the data representing the real brain response (e.g., the artifacts can be removed from the active TMS fMRI measurement). The data representing the real brain response can be used, for example, to adapt the TMS therapy protocol.

[0033] FIG. 6 is a block diagram of an example computer system in accordance with an embodiment. Computer system 600 may be used to implement the systems and methods described herein. In some embodiments, the computer system 600 may be a workstation, a notebook computer, a tablet device, a mobile device, a multimedia device, a network server, a mainframe, one or more controllers, one or more microcontrollers, or any other general-purpose or application-specific computing device. The computer system 600 may operate autonomously or semi-autonomously, or may read executable software instructions from the memory or storage device 616 or a computer-readable medium (e.g., a hard drive, a CD-ROM, flash memory), or may receive instructions via the input device 620 from a user, or any other source logically connected to a computer or device, such as another networked computer or server. Thus, in some embodiments, the computer system 600 can also include any suitable device for reading computer-readable storage media.

[0034] Data, such as data acquired with an imaging system (e.g., a magnetic resonance imaging (MRI) system) may be provided to the computer system 600 from a data storage device 616, and these data are received in a processing unit 602. In some embodiment, the processing unit 602 includes one or more processors. For example, the processing unit 602 may include one or more of a digital signal processor (DSP) 604, a microprocessor unit (MPU) 606, and a graphics processing unit (GPU) 608. The processing unit 602 also includes a data acquisition unit 610 that is configured to electronically receive data to be processed. The DSP 604, MPU 606, GPU 608, and data acquisition unit 610 are all coupled to a communication bus 612. The communication bus 612 may be, for example, a group of wires, or a hardware used for switching data between the peripherals or between any components in the processing unit 602.

[0035] The processing unit 602 may also include a communication port 614 in electronic communication with other devices, which may include a storage device 616, a display 618, and one or more input devices 620. Examples of an input device 620 include, but are not limited to, a keyboard, a mouse, and a touch screen through which a user can provide an input. The storage device 616 may be configured to store data, which may include data such as, for example, E- field data, combined E-fields of at least two different coil elements, EEG data, fMRI data, etc. whether these data are provided to, or processed by, the processing unit 602. The display 618 may be used to display images and other information, such as magnetic resonance images, patient health data, and so on.

[0036] The processing unit 602 can also be in electronic communication with a network 622 to transmit and receive data and other information. The communication port 614 can also be coupled to the processing unit 602 through a switched central resource, for example the communication bus 612. The processing unit can also include temporary storage 624 and a display controller 626. The temporary storage 624 is configured to store temporary information. For example, the temporary storage 624 can be a random access memory.

[0037] FIG. 7 is a block diagram of an example electroencephalography (EEG) system in accordance with an embodiment. EEG system 700 can be configured to acquire electrophysiological signals indicative of neuronal activity. The electrophysiological signals measured and acquired with the EEG system 700 are acquired on a number of EEG electrodes 702, or sensors, for example, of the 10-20 international electrode placement system.

[0038] During measurement of neuronal activity with the EEG system 700, a continuous stream of voltage data representative of an electrophysiological signal can be detected by the electrodes 702, which are coupled to the subject’s scalp, and the acquired signals can be sampled and digitized. Specifically, an amplifier 704 in communication with the electrodes 702 can be used to amplify the acquired signals, after which the amplified signals are sent to an analog-to-digital (A/D) converter 706 that converts the signals from analog to digital format. The acquired signals can also undergo additional preprocessing in order to remove artifacts, such as those due to data collection and physiological causes. The digital signals can be sent to a processor 708 that processes the signals. The processor 708 is also configured to store the processed or unprocessed signals in a memory 710, and to display the signals on a display 712.

[0039] FIG. 8 is a block diagram of an example magnetic resonance imaging (MRI) system in accordance with an embodiment. MRI system 800 that may be used to perform the methods described herein, for example, fMRI scans. The MRI system 800 includes an operator workstation 802, which may include a display 804, one or more input devices 806 (e.g., a keyboard and mouse), and a processor 808. The processor 808 may include a commercially available programmable machine running a commercially available operating system. The operator workstation 802 provides the operator interface that facilitates entering scan parameters (e g., a scan prescription) into the MRI system 800. The operator workstation 802 may be coupled to different servers, including, for example, a pulse sequence server 810, a data acquisition server 812, a data processing server 814, and a data store server 816. The operator workstation 802 and the servers 810, 812, 814, and 816 may be connected via a communication system 840, which may include any suitable network connection, whether wired, wireless, or a combination of both.

[0040] The pulse sequence server 810 functions in response to instructions provided by the operator workstation 802 to operate a gradient system 818 and a radiofrequency (“RF”) system 820. Gradient waveforms for performing a prescribed scan are produced and applied to the gradient system 818, which excites gradient coils in an assembly 822 to produce the magnetic field gradients G_x, G_y, and G_z that are used for spatially encoding magnetic resonance signals. The gradient coil assembly 822 forms part of a magnet assembly 824 that includes a polarizing magnet 826 and a whole-body RF coil 828 and/or a local coil (not shown).

[0041] RF waveforms are applied by the RF system 120 to the RF coil 128, or a separate local coil, to perform the prescribed magnetic resonance pulse sequence. Responsive magnetic resonance signals detected by the RF coil 828, or a separate local coil, are received by the RF system 820. The responsive magnetic resonance signals may be amplified, demodulated, filtered, and digitized under direction of commands produced by the pulse sequence server 810. The RF system 820 includes an RF transmitter for producing a wide variety of RF pulses used in MRI pulse sequences. The RF transmitter is responsive to the prescribed scan and direction from the pulse sequence server 810 to produce RF pulses of the desired frequency, phase, and pulse amplitude waveform. The generated RF pulses may be applied to the whole-body RF coil 828 or to one or more local coils or coil arrays.

[0042] The RF system 820 also includes one or more RF receiver channels. Each RF receiver channel includes an RF preamplifier that amplifies the magnetic resonance signal received by the coil 828,829 to which it is connected, and a detector that detects and digitizes the I and Q quadrature components of the received magnetic resonance signal. The magnitude of the received magnetic resonance signal may, therefore, be determined at any sampled point by the square root of the sum of the squares of the I and Q components:

M = l² + Q² (3) and the phase of the received magnetic resonance signal may also be determined according to the following relationship:

<P = tan-¹ ) (4)

[0043] The pulse sequence server 810 may receive patient data from a physiological acquisition controller 830. By way of example, the physiological acquisition controller 830 may receive signals from a number of different sensors connected to the patient, such as electrocardiograph (“ECG”) signals from electrodes, or respiratory signals from a respiratory bellows or other respiratory monitoring device. Such signals are typically used by the pulse sequence server 810 to synchronize, or “gate,” the performance of the scan with the subject’s heartbeat or respiration. [0044] The pulse sequence server 810 may also connect to a scan room interface circuit 832 that receives signals from various sensors associated with the condition of the patient and the magnet system. Through the scan room interface circuit 832, a patient positioning system 834 can receive commands to move the patient to desired positions during the scan.

[0045] The digitized magnetic resonance signal samples produced by the RF system 820 are received by the data acquisition server 812. The data acquisition server 812 operates in response to instructions downloaded from the operator workstation 802 to receive the real-time magnetic resonance data and provide buffer storage, such that no data is lost by data overrun. In some scans, the data acquisition server 812 passes the acquired magnetic resonance data to the data processor server 814. In scans that require information derived from acquired magnetic resonance data to control the further performance of the scan, the data acquisition server 812 may be programmed to produce such information and convey it to the pulse sequence server 810. For example, during pre-scans, magnetic resonance data may be acquired and used to calibrate the pulse sequence performed by the pulse sequence server 810. As another example, navigator signals may be acquired and used to adjust the operating parameters of the RF system 820 or the gradient system 818, or to control the view order in which k-space is sampled. In still another example, the data acquisition server 812 may also process magnetic resonance signals used to detect the arrival of a contrast agent in a magnetic resonance angiography (“MRA”) scan. For example, the data acquisition server 812 may acquire magnetic resonance data and process it in real-time to produce information that is used to control the scan.

[0046] The data processing server 814 receives magnetic resonance data from the data acquisition server 812 and processes it in accordance with instructions downloaded from the operator workstation 802. Such processing may include, for example, reconstructing two- dimensional or three-dimensional images by performing a Fourier transformation of raw k-space data, performing other image reconstruction algorithms (e.g., iterative or back-projection reconstruction algorithms), applying filters to raw k-space data or to reconstructed images, generating functional magnetic resonance images, or calculating motion or flow images.

[0047] Images reconstructed by the data processing server 814 are conveyed back to the operator workstation 802 for storage. Real-time images may be stored in a data base memory cache (not shown in FIG. 8), from which they may be output to operator display 804 or a display 836. Batch mode images or selected real time images may be stored in a host database on disc storage 838. When such images have been reconstructed and transferred to storage, the data processing server 814 notifies the data store server 816 on the operator workstation 802. The operator workstation 802 may be used by an operator to archive the images, produce films, or send the images via a network to other facilities.

[0048] The MRI system 800 may also include one or more networked workstations 842. By way of example, a networked workstation 842 may include a display 844, one or more input devices 846 (e.g., a keyboard and mouse), and a processor 848. The networked workstation 842 may be located within the same facility as the operator workstation 802, or in a different facility, such as a different healthcare institution or clinic. [0049] The networked workstation 842 may gain remote access to the data processing server 814 or data store server 816 via the communication system 840. Accordingly, multiple networked workstations 842 may have access to the data processing server 814 and the data store server 816. In this manner, magnetic resonance data, reconstructed images, or other data may be exchanged between the data processing server 814 or the data store server 816 and the networked workstations 842, such that the data or images may be remotely processed by a networked workstation 842. This data may be exchanged in any suitable format, such as in accordance with the transmission control protocol (TCP), the internet protocol (IP), or other known or suitable protocols.

[0050] Computer-executable instructions for constructing an epileptogenic network (e.g., SEEN or MEEN) using non-invasive sensor data or invasive sensor data and calculating node criticality according to the above-described methods may be stored on a form of computer readable media. Computer readable media includes volatile and nonvolatile, removable, and non-removable media implemented in any method or technology for storage of information such as computer readable instructions, data structures, program modules or other data. Computer readable media includes, but is not limited to, random access memory (RAM), read-only memory (ROM), electrically erasable programmable ROM (EEPROM), flash memory or other memory technology, compact disk ROM (CD-ROM), digital volatile disks (DVD) or other optical storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other medium which can be used to store the desired instructions and which may be accessed by a system (e g., a computer), including by internet or other computer network form of access.

[0051] The present technology has been described in terms of one or more preferred embodiments, and it should be appreciated that many equivalents, alternatives, variations, and modifications, aside from those expressly stated, are possible and within the scope of the invention.

Claims

1 . A method for controlling E-field intensity for a scalp region and a target brain region of a subject using a multichannel transcranial magnetic stimulation (TMS) coil array having a plurality of TMS coils and a plurality of coil elements, the method comprising: calculating, using a processor device, an electric field (E-field) for each coil element in the mTMS coil array; combining, using the processor device, the E-field of two or more coil elements to create a predetermined E-field intensity for the scalp region and a predetermined E-field intensity for the target brain region; determining, using the processor device, an electrical signal for each coil element based on the calculated E-field corresponding to each coil element; applying, using a signal generator, the electrical signals determined for the two or more coil elements with combined E-fields simultaneously to the two or more coil elements; and applying, using the signal generator, the electrical signals determined for each coil element without combined E-fields to the corresponding coil element.

2. The method according to claim 1, wherein each TMS coil in the mTMS coil array comprises a single coil element.

3. The method according to claim 1, wherein each TMS coil in the mTMS coil array comprises three coil elements.

4. The method according to claim 3, wherein each TMS coil is a 3-axis TMS coil.

5. The method according to claim 1, wherein the E-fields of the two or more coil elements are combined using an optimization method to minimize one of the E-field intensity for the scalp region or the E-field intensity for the target brain region.

6. The method according to claim 1, wherein the predetermined E-field intensity for the scalp region and the predetermined E-field intensity for the target brain region are configured to mitigate scalp artifacts during an active TMS application for one or more of a concurrent electroencephalography (EEG) measurement or a concurrent functional magnetic resonance imaging (fMRI) measurement.

7. The method according to claim 6, wherein the predetermine E-field for the scalp region is a minimized E-field intensity and the predetermined E-field intensity for the target brain region is a maximized E-field intensity.

8. The method according to claim 1, wherein the predetermined E-field intensity for the scalp region and the predetermined E-field intensity for the target brain region are configured to generate a sham TMS condition.

9. The method according to claim 8, wherein the predetermined E-field intensity for the target brain region is a minimized E-field intensity and the predetermined E-field intensity for the scalp region is a maximized E-field intensity.

10. The method according to claim 1, wherein the predetermined E-field intensity for the scalp region and the predetermined E-field intensity for the target brain region are configured to reduce muscle and nerve activation in the scalp region during an active TMS application.

11. A system for controlling E-field intensity for a scalp region and a target brain region of a subject using a multichannel transcranial magnetic stimulation (TMS) coil array having a plurality of TMS coils and a plurality of coil elements, the system comprising: a memory that stores one or more computer readable media that includes instructions; and one or more processor devices configured to execute the instructions of the computer readable media to: calculate an electric field (E-field) for each coil element in the mTMS coil array; combine the E-field of two or more coil elements to create a predetermined E-field intensity for the scalp region and a predetermined E-field intensity for the target brain region; determine an electrical signal for each coil element based on the calculated E-field corresponding to each coil element; apply the electrical signals determined for the two or more coil elements with combined E-fields simultaneously to the two or more coil elements; and apply the electrical signals determined for each coil element without combined E-fields to the corresponding coil element.

12. The system according to claim 11, wherein each TMS coil in the mTMS coil array comprises a single coil element .

13. The system according to claim 11, wherein each TMS coil in the mTMS coil array comprises three coil elements.

14. The system according to claim 13, wherein each TMS coil is a 3-axis TMS coil.

15. The system according to claim 11, wherein the E-fields of the two or more coil elements are combined using an optimization method to minimize one of the E-field intensity for the scalp region or the E-field intensity for the target brain region.

16. The system according to claim 11, wherein the predetermined E-field intensity for the scalp region and the predetermined E-field intensity for the target brain region are configured to mitigate scalp artifacts during an active TMS application for one or more of a concurrent electroencephalography (EEG) measurement or a concurrent functional magnetic resonance imaging (fMRI) measurement.

17. The system according to claim 16, wherein the predetermine E-field for the scalp region is a minimized E-field intensity and the predetermined E-field intensity for the target brain region is a maximized E-field intensity.

18. The system according to claim 11, wherein the predetermined E-field intensity for the scalp region and the predetermined E-field intensity for the target brain region are configured to generate a sham TMS condition.

19. The system according to claim 18, wherein the predetermined E-field intensity for the target brain region is a minimized E-field intensity and the predetermined E-field intensity for the scalp region is a maximized E-field intensity.

20. The system according to claim 11, wherein the predetermined E-field intensity for the scalp region and the predetermined E-field intensity for the target brain region are configured to reduce muscle and nerve activation in the scalp region during an active TMS application.