CN119455253A - Closed-loop feedback transcranial alternating current stimulation system and method - Google Patents
Closed-loop feedback transcranial alternating current stimulation system and method Download PDFInfo
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Abstract
本申请涉及一种闭环反馈经颅交流电刺激系统及方法。闭环反馈经颅交流电刺激系统包括：相位刺激系统，用于生成多种电刺激信号，并基于电刺激信号对大脑中不同脑区进行刺激；各电刺激信号之间具有预设相位差；脑电采集系统，用于在相位刺激系统对大脑进行刺激预设时间后，采集大脑的脑电信号；评估反馈系统，与相位刺激系统及脑电采集系统均相连接，用于对脑电采集系统采集的脑电信号进行评估，并基于评估结果对电刺激信号进行调整。上述闭环反馈经颅交流电刺激系统可以基于大脑的实时振荡信号对波形信号进行灵活调整，解决了现有技术中存在的激波形单一，难以精确匹配个体差异，无法适应动态脑网络状态变化等问题。
The present application relates to a closed-loop feedback transcranial alternating current stimulation system and method. The closed-loop feedback transcranial alternating current stimulation system includes: a phase stimulation system for generating a variety of electrical stimulation signals, and stimulating different brain regions in the brain based on the electrical stimulation signals; each electrical stimulation signal has a preset phase difference; an EEG acquisition system for collecting EEG signals of the brain after the phase stimulation system stimulates the brain for a preset time; an evaluation feedback system connected to both the phase stimulation system and the EEG acquisition system, for evaluating the EEG signals collected by the EEG acquisition system, and adjusting the electrical stimulation signals based on the evaluation results. The above-mentioned closed-loop feedback transcranial alternating current stimulation system can flexibly adjust the waveform signal based on the real-time oscillation signal of the brain, solving the problems existing in the prior art such as the single stimulation waveform, the difficulty in accurately matching individual differences, and the inability to adapt to changes in dynamic brain network states.
Description
Technical Field
The application relates to the technical field of medical equipment, in particular to a closed-loop feedback transcranial alternating current stimulation system and method.
Background
Transcranial alternating current stimulation (TRANSCRANIAL ALTERNATING current stimulation, tcacs) is a non-invasive effective treatment for brain cognitive function regulation, and the existing tcacs stimulation modes are various, for example, cognitive dysfunction and cognitive function impairment are particularly common in patients suffering from Alzheimer's Disease (AD), craniocerebral injury (traumatic brain injury, TBI) and cerebral stroke, and tcacs are expected to improve cognitive dysfunction or cognitive function impairment by directly interfering with ongoing oscillatory activity of the brain by applying sinusoidal current to the intact scalp. The conventional tACS still has some defects and limitations, and particularly has the problems that the stimulation waveform is single, the individual difference is difficult to be matched accurately, the dynamic brain network state change cannot be adapted and the like in the application of multi-brain-area stimulation.
Disclosure of Invention
Based on this, there is a need to provide a closed-loop feedback transcranial alternating current stimulation system and method that address the problems in the related art.
To achieve the above object, in a first aspect, the present application provides a closed-loop feedback transcranial alternating current stimulation system, comprising:
The phase stimulation system is used for generating a plurality of electric stimulation signals and stimulating different brain areas in the brain based on the electric stimulation signals, wherein a preset phase difference exists between the electric stimulation signals;
the brain electrical acquisition system is used for acquiring brain electrical signals of the brain after the phase stimulation system stimulates the brain for a preset time;
And the evaluation feedback system is connected with the phase stimulation system and the electroencephalogram acquisition system, and is used for evaluating the electroencephalogram signals acquired by the electroencephalogram acquisition system and adjusting the electric stimulation signals based on an evaluation result.
In some of these embodiments, the phase stimulation system comprises:
A parameter input device for setting parameters for generating a voltage waveform signal, wherein the setting parameters comprise peak current for generating the voltage waveform signal, waveform mode of the voltage waveform signal, frequency of the voltage waveform signal, phase difference of different voltage waveform signals and duration time of the voltage waveform signal;
The voltage-controlled waveform generating device is connected with the parameter input device and is used for generating a voltage waveform signal based on the setting parameter;
the Howland constant current source is connected with the voltage-controlled waveform generating device and is used for generating the electric stimulation signal based on the voltage waveform signal;
and the electric stimulation signal output device is connected with the Howland constant current source and is used for stimulating different brain areas in the brain based on the electric stimulation signal.
In some of these embodiments, the phase stimulation system further comprises:
And the waveform measuring device is connected with the voltage-controlled waveform generating device and the electric stimulation signal output device and is used for sampling and detecting the voltage waveform signal and controlling the electric stimulation signal output device to stop outputting the electric stimulation signal when the detection result is abnormal.
In some embodiments, the electrical stimulation signal output device comprises a brain nail, the brain electrical acquisition system comprises the brain nail and an brain electrical signal collection device, and the closed-loop feedback transcranial alternating current stimulation system further comprises:
the single-pole double-throw relay is connected with the brain nail, the electroencephalogram signal collecting device and the Howland constant current source.
In some embodiments, the electroencephalogram signal comprises a first electroencephalogram signal of a first brain region and a second electroencephalogram signal of a second brain region, and the assessment feedback system comprises:
The preprocessing module is connected with the electroencephalogram acquisition system and is used for preprocessing and band-pass filtering the electroencephalogram signals to obtain nerve oscillation signals, wherein the nerve oscillation signals comprise first nerve oscillation signals corresponding to the first electroencephalogram signals and second nerve oscillation signals corresponding to the second electroencephalogram signals;
The conversion module is connected with the preprocessing module and is used for carrying out Hilbert conversion on the nerve oscillation signal to obtain instant phase information, and the instant phase information comprises a first instant phase and a second instant phase;
The processing module is connected with the transformation module and is used for obtaining the phase difference between the first electroencephalogram signal and the second electroencephalogram signal based on the instant phase information;
the judging module is connected with the processing module and is used for comparing and evaluating the phase difference with a target phase difference to obtain an evaluation result;
And the parameter adjustment module is connected with the judgment module and is used for adjusting the electric stimulation signal based on the evaluation result.
In a second aspect, the present application also provides a closed-loop feedback transcranial alternating current stimulation method, the closed-loop feedback transcranial alternating current stimulation method comprising:
Generating a plurality of electric stimulation signals, and stimulating different brain areas in the brain based on the electric stimulation signals, wherein a preset phase difference exists between the electric stimulation signals;
After the electrical stimulation signals stimulate the brain for a preset time, acquiring brain electrical signals of the brain;
and evaluating the electroencephalogram signals, and adjusting the electric stimulation signals based on the evaluation result.
In some embodiments, after the electrical stimulation signal is adjusted based on the evaluation result, the method further comprises repeating the above steps at least once, wherein the generated multiple electrical stimulation signals are all electrical stimulation signals adjusted based on the evaluation result of the previous step.
In some of these embodiments, the generating the plurality of electrical stimulation signals includes:
Setting parameters for generating a voltage waveform signal, wherein the setting parameters comprise peak current of the voltage waveform signal, waveform mode of the voltage waveform signal, frequency of the voltage waveform signal, phase difference of different voltage waveform signals and duration time of the voltage waveform signal;
generating a voltage waveform signal based on the set parameter;
The electrical stimulation signal is generated based on the voltage waveform signal.
In some embodiments, the electroencephalogram signal comprises a first electroencephalogram signal of a first brain region and a second electroencephalogram signal of a second brain region, the evaluating the electroencephalogram signal and adjusting the electrical stimulation signal based on the evaluation result comprises:
Preprocessing and band-pass filtering the electroencephalogram signals to obtain nerve oscillation signals, wherein the nerve oscillation signals comprise first nerve oscillation signals corresponding to the first electroencephalogram signals and second nerve oscillation signals corresponding to the second electroencephalogram signals;
Performing Hilbert transformation on the neural oscillation signal to obtain instant phase information, wherein the instant phase information comprises a first instant phase and a second instant phase;
processing the phase information to obtain a phase difference between the first electroencephalogram signal and the second electroencephalogram signal;
Comparing and evaluating the phase difference with a target phase difference to obtain an evaluation result;
and adjusting the electrical stimulation signal based on the evaluation result.
In one embodiment, the neural oscillation signal is Hilbert transformed based on the following formula to obtain the instantaneous phase information:
Wherein, Is the first instantaneous phase; is in a second instant phase, x 1 (t) is a first nerve oscillation signal at the moment of t of a first brain region, x 2 (t) is a second nerve oscillation signal at the moment of t of a second brain region, P and V are cauchy main values, tau is an integral variable, x 1 (t) is a nerve oscillation signal of the integral variable tau corresponding to the first brain region, and x 2 (tau) is a nerve oscillation signal of the integral variable tau corresponding to the second brain region;
processing the phase information based on the following formula to obtain a phase difference between the first electroencephalogram signal and the second electroencephalogram signal:
Wherein, A phase difference between the first electroencephalogram signal and the second electroencephalogram signal; an instantaneous phase of a first neural oscillating signal at a time t n for the first brain region; The method comprises the steps of obtaining a first brain region, obtaining a first nerve oscillation signal of the first brain region, obtaining a second brain region, obtaining a first brain signal of the first brain region, obtaining a second brain signal of the second brain region, obtaining an instant phase of the second nerve oscillation signal of the second brain region at a time t n, wherein n=1, 2.
The adjusting the electric stimulation signal based on the evaluation result comprises adjusting and reducing the stimulation time of the electric stimulation signal and reducing the stimulation intensity of the electric stimulation signal if the difference between the phase difference and the target phase difference is smaller than a preset phase, and adjusting and increasing the stimulation time of the electric stimulation signal and enhancing the stimulation intensity of the electric stimulation signal if the difference between the phase difference and the target phase difference is larger than or equal to the preset phase.
According to the closed-loop feedback transcranial alternating current stimulation system and method, by arranging the phase stimulation system, the electroencephalogram acquisition system and the evaluation feedback system, the phase stimulation system can generate electric stimulation signals with preset phase differences, coupling of cross-brain-region and multi-channel neural oscillation can be achieved, the electric stimulation signals can be flexibly adjusted based on real-time brain electrical signals of a brain, and the problems that shock waveforms are single, individual differences are difficult to match accurately, dynamic brain network state changes cannot be adapted and the like in the prior art are solved.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments or the conventional techniques of the present application, the drawings required for the descriptions of the embodiments or the conventional techniques will be briefly described below, and it is apparent that the drawings in the following description are only some embodiments of the present application, and other drawings may be obtained according to the drawings without inventive effort for those skilled in the art.
FIG. 1 is a block diagram of a closed loop feedback transcranial AC stimulation system according to one embodiment of the present application;
FIG. 2 is a block diagram of a phase stimulation system in a closed loop feedback transcranial AC stimulation system according to one embodiment of the present application;
FIG. 3 is a block diagram of an evaluation feedback system in a closed-loop feedback transcranial AC stimulation system according to one embodiment of the present application;
fig. 4 and 5 are flowcharts of a closed-loop feedback transcranial alternating current stimulation method according to another embodiment of the present application.
The reference numerals indicate 10, a phase stimulation system, 101, a parameter input device, 102, a voltage-controlled waveform generating device, 103, a Howland constant current source, 104, an electric stimulation signal output device, 20, an electroencephalogram acquisition system, 30, an evaluation feedback system, 301, a preprocessing module, 302, a conversion module, 303, a processing module, 304, a judging module, 305, a parameter adjusting module and 40, a brain area to be tested.
Detailed Description
The present application will be described in further detail with reference to the drawings and examples, in order to make the objects, technical solutions and advantages of the present application more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the application.
Transcranial alternating current stimulation (tpacs) is a non-invasive effective treatment for brain cognitive function regulation, and the existing tpacs are various in stimulation mode, for example, cognitive dysfunction and cognitive function impairment are particularly common in patients suffering from Alzheimer's Disease (AD), craniocerebral injury (traumatic brain injury, TBI) and cerebral stroke, and the tpacs directly interfere with ongoing oscillatory activity of the brain by applying sinusoidal current to the intact scalp, thereby hopefully improving cognitive dysfunction or cognitive function impairment. there are still some drawbacks and limitations to tcacs, especially in the application of stimulation to the brain regions. Because of the complex design of the personalized stimulation scheme of the multiple brain regions, different functions and nerve loops of regulation need to be considered, although a high-precision and high-strength tACS scheme exists, a regulation scheme for coordinating the activity mode between the brain regions based on different tasks (such as movement, memory, decision, and the like) is still lacking.
Neural oscillation coupling refers to a synchronous activity between different populations of neurons in the brain, which typically exhibits an oscillation pattern of a particular frequency. In advanced cognitive functions such as attention, memory coding and information transfer, neuronal populations in different regions of the brain oscillate at the same frequency and their phase relationship is often expressed as a stable coupled relationship with a fixed phase difference. The neural oscillation coupling phase difference refers to the phase relation between two or more neural oscillators, has important significance in neuroscience, can reflect the synchronization degree between different neuron groups or brain areas, and reveals the information transmission direction. The phase-coupling differences for different frequency ranges may be related to different neural functions. For example, gamma wave phase coupling may be associated with perception and attention, while theta wave phase coupling may be associated with memory and navigation. A particular phase relationship may also be associated with a particular cognitive or behavioral state, indicating cooperative activity of a particular brain region under certain tasks or states. At present, a transcranial alternating current stimulation system based on phase difference does not exist. For example, during working memory, the coupling between the prefrontal cortex (prefrontal cortex, PFC) and the hippocampus (hippocampus, HPC) is predominantly represented by the theta band phase coupling of PFC and HPC waves.
In one embodiment, referring to fig. 1, the present application provides a closed-loop feedback transcranial alternating current stimulation system, which may include a phase stimulation system 10, an electroencephalogram acquisition system 20 and an evaluation feedback system 30, where the phase stimulation system 10 is configured to generate a plurality of electrical stimulation signals, and to stimulate different brain regions in the brain based on the electrical stimulation signals, each electrical stimulation signal has a preset phase difference, the electroencephalogram acquisition system 20 is configured to acquire brain electrical signals after the phase stimulation system stimulates the brain (i.e. the brain region 40 to be tested in fig. 1) for a preset time, and the evaluation feedback system 30 is connected with the phase stimulation system 10 and the electroencephalogram acquisition system 20, and is configured to evaluate the brain electrical signals acquired by the electroencephalogram acquisition system 20 and adjust the electrical stimulation signals based on the evaluation results.
In the closed-loop feedback transcranial alternating current stimulation system, by arranging the phase stimulation system 10, the electroencephalogram acquisition system 20 and the evaluation feedback system 30, the phase stimulation system 10 can generate electric stimulation signals with preset phase differences, can realize coupling of cross-brain-area and multi-channel neural oscillation, can flexibly adjust the electric stimulation signals based on real-time brain electrical signals of the brain, and solves the problems that shock waveforms are single, individual differences are difficult to match accurately, dynamic brain network state change cannot be adapted and the like in the prior art.
As an example, referring to fig. 2, the phase stimulation system may include a parameter input device 101, a voltage-controlled waveform generating device 102, a howlan constant current source 103, and an electrical stimulation signal output device 104, where the parameter input device 101 is configured to set setting parameters for generating a voltage waveform signal, the setting parameters include a peak current for generating the voltage waveform signal, a waveform manner of the voltage waveform signal, a frequency of the voltage waveform signal, a phase difference of different voltage waveform signals, and a duration of the voltage waveform signal, the voltage-controlled waveform generating device 102 is connected to the parameter input device 101 and is configured to generate a voltage waveform signal based on the setting parameters, the howlan constant current source 103 is connected to the voltage-controlled waveform generating device 102 and is configured to generate the electrical stimulation signal based on the voltage waveform signal, and the electrical stimulation signal output device 104 is connected to the howlan constant current source 103 and is configured to stimulate different brain regions in the brain based on the electrical stimulation signal.
As an example, the parameter input device 101 is configured to set a peak current used to generate the voltage waveform signal, a waveform mode of the voltage waveform signal (including but not limited to sine wave, square wave, triangular wave, and a mixed waveform thereof), a frequency of the voltage waveform signal, a phase difference of different voltage waveform signals, and a duration of the voltage waveform signal.
Specifically, the frequency of each voltage waveform signal can be freely adjusted within a specified frequency band, for example, the voltage waveform signals can be adjusted to oscillate such as delta oscillation (the frequency is 0.5-4 Hz), theta oscillation (4-8 Hz), alpha oscillation (8-12 Hz), beta oscillation (13-30 Hz) and low frequency and high frequency gamma oscillation (30-150 Hz, wherein the low frequency is 30-70Hz and the high frequency is 70-150 Hz) so as to match different brain regions, different nerve oscillation modes and specific phase difference requirements. The high sensitivity can enable the closed-loop feedback transcranial alternating current stimulation system to be customized according to the specific type, degree and brain network state of the nerve dysfunction of a patient, and the treatment effect can be remarkably improved.
The phase stimulation system 10 of the present application can apply electrical stimulation signals corresponding to functional rhythms in a specific brain region, and can trigger or adjust specific neural activity rhythms in a specific region of the brain as required to simulate or enhance a natural brain wave pattern, thereby realizing regulation or optimization of brain functions. These rhythmic waveform signals generally correspond to various cognitive or physiological states of the brain, such as concentration, relaxation, sleep or memory processes, and can be precisely matched to the physiological characteristics and needs of the target brain region, thereby effectively supporting the exertion and promotion of related functions.
As an example, the voltage-controlled waveform generating means 102 may generate the voltage waveform signal that meets the requirements through a DAC (digital-to-analog converter) circuit according to the setting parameters set by the parameter input means 101.
As an example, the howlan constant current source 103 may obtain the electrical stimulation signal based on the voltage waveform signal according to a calculation formula of Howland model and according to a proportional relationship between current and voltage, and the electrical stimulation signal may be a current signal.
As an example, the electrical stimulation signal output device 104 may include, but is not limited to, brain nails (not shown) or electrodes (not shown), and in this embodiment, the electrical stimulation signal output device 104 may include brain nails, where the number of the brain nails may be plural, and each brain nail is disposed in a different brain region.
As an example, the phase stimulation system may further include a waveform measuring device (not shown) connected to the voltage-controlled waveform generating device 102 and the electrical stimulation signal output device 104, where the waveform measuring device is configured to sample and detect the voltage waveform signal, and control the electrical stimulation signal output device 104 to stop outputting the electrical stimulation signal when the detection result is abnormal. By the waveform measuring device determining the quality of the voltage waveform signal generated by the voltage-controlled waveform generating device 102 in real time, it is possible to determine whether or not an abnormality has occurred in the electrical stimulation output device 104 (for example, to determine whether or not the electrical stimulation output device is detached, etc.).
As an example, the brain electrical collection system may include the brain nail and brain electrical signal collection device (not shown), and the closed loop feedback transcranial alternating current stimulation system may further include a single pole double throw relay (not shown) connected to the brain nail, the brain electrical signal collection device, and the Howland constant current source 103. That is, in this embodiment, the brain nail is shared by the electroencephalogram acquisition system 20 and the phase stimulation system 10, that is, the electrical stimulation output device 104 of the phase stimulation system 10 and the acquisition device of the electroencephalogram acquisition system 20 acquire brain electrical signals are the same device. However, since the signals of the phase stimulation system 10 and the electroencephalogram acquisition system 20 have a huge difference, protection of the closed-loop feedback transcranial alternating current stimulation system is required, and no influence of the electric stimulation part on electroencephalogram acquisition is ensured. Based on this, by setting the single-pole double-throw relay, the electroencephalogram acquisition system 20 can be disconnected from acquiring the electroencephalogram signals when the phase stimulation system 10 performs electric stimulation on the brain region, and the phase stimulation system 10 can be disconnected from performing electric stimulation on the brain region when the electroencephalogram signals are acquired by the electroencephalogram stimulation system 20, so that the accuracy and the safety of the electroencephalogram signals acquired by the electroencephalogram acquisition system 20 are ensured.
The electroencephalogram signals comprise a first electroencephalogram signal of a first brain region and a second electroencephalogram signal of a second brain region by way of example, the evaluation feedback system 30 can comprise a preprocessing module 301, a transformation module 302, a processing module 303, a judging module 304 and a parameter adjusting module 305, wherein the preprocessing module 301 is connected with the electroencephalogram acquisition system 20 and is used for preprocessing and band-pass filtering the electroencephalogram signals to obtain nerve oscillation signals, the nerve oscillation signals comprise a first nerve oscillation signal corresponding to the first electroencephalogram signal and a second nerve oscillation signal corresponding to the second electroencephalogram signal, the transformation module 302 is connected with the preprocessing module 301 and is used for carrying out Hilbert transformation on the nerve oscillation signals to obtain instant phase information comprising a first instant phase and a second instant phase, the processing module 303 is connected with the transformation module 302 and is used for obtaining the phase difference between the first electroencephalogram signal and the second electroencephalogram signal based on the instant phase information, the judging module 303 is connected with the processing module and is used for carrying out evaluation on the phase difference adjustment to obtain the evaluation result, and the evaluation result is used for carrying out the adjustment on the phase difference adjustment module 304.
As an example, the transforming module 302 performs Hilbert transformation on the neural oscillation signal based on the following formula to obtain the first instantaneous phase and the second instantaneous phase:
Wherein, Is the first instantaneous phase; Is a second instant phase, x 1 (t) is a first nerve oscillation signal at the moment of t of a first brain region, x 2 (t) is a second nerve oscillation signal at the moment of t of a second brain region, P and V are cauchy main values, tau is an integral variable, x 1 (tau) is a nerve oscillation signal of the integral variable tau corresponding to the first brain region, and x 2 (tau) is a nerve oscillation signal of the integral variable tau corresponding to the second brain region.
As an example, the processing module 303 obtains the phase difference between the first electroencephalogram signal and the second electroencephalogram signal based on the following formula:
Wherein, A phase difference between the first electroencephalogram signal and the second electroencephalogram signal; an instantaneous phase of a first neural oscillating signal at a time t n for the first brain region; The method comprises the steps of obtaining a first brain region, obtaining a first nerve oscillation signal of the first brain region, obtaining a second brain region, obtaining a first brain signal of the first brain region, obtaining a second brain signal of the second brain region, obtaining an instant phase of the second nerve oscillation signal of the second brain region at a time t n, wherein n=1, 2.
As an example, the parameter adjustment module 305 adjusts the electrical stimulation signal based on the evaluation result by adjusting to decrease the stimulation time of the electrical stimulation signal and decrease the stimulation intensity of the electrical stimulation signal if the difference between the phase difference and the target phase difference is smaller than a preset phase, and adjusting to increase the stimulation time of the electrical stimulation signal and increase the stimulation intensity of the electrical stimulation signal if the difference between the phase difference and the target phase difference is greater than or equal to a preset phase.
As an example, the closed loop feedback transcranial alternating current stimulation system may further include a safety module (not shown) connected to the parameter adjustment module 305 and the phase stimulation system 10, where the safety module is configured to determine whether the current intensity of the electrical stimulation signal adjusted by the parameter adjustment module 305 is 0 or whether the current intensity is greater than a safety threshold, if so, stopping electrical stimulation, and if not, performing electrical stimulation on different brain regions based on the adjusted electrical stimulation signal.
In a specific example, a mouse may be subjected to craniotomy, 4 brain nails are implanted in the brain of the mouse, the 4 brain nails may be arranged according to a preset arrangement rule, and the evaluation feedback system 30 is a software running on a PC. The assessment feedback system 30 is connected to the phase stimulation system 10 via a USB CDC or serial port. The evaluation feedback system 30 requires the phase stimulation system 10 to generate two sine wave current signals with a maximum peak current of 5ma, the phase difference between the two signals being 90 degrees. The phase stimulation system 10 generates two output tables of sine waves according to the parameters, and the phase difference of the output tables is 90 degrees. The voltage controlled waveform generation means 102 converts the output table into a sinusoidal voltage signal using the circuitry of the DAC. A circuit waveform (i.e., the electrical stimulation signal) is generated using the Howland constant current source, e.g., using a power op-amp of TI, e.g., OPA462, OPA455, OPA445, OPA452, in combination with a high voltage positive and negative power source, e.g., + -75V. Such high voltages are used because electrical stimulation is a current stimulus, and the impedance between the two stimulus electrodes varies, and the magnitude of the impedance is greater, so that the peak is calculated to be the required driving voltage.
As an example, the time of one stimulation of the phase stimulation system 10 may be 5 seconds, and the interval time between the stimulation and the acquisition of the brain electrical signal, that is, the preset time may be 15 seconds, and the time for continuously acquiring the brain electrical signal of the brain area 40 may be 30 seconds.
In another embodiment, referring to fig. 4 in conjunction with fig. 1 to 3, the present application further provides a closed-loop feedback transcranial ac stimulation method, which may include the steps of:
s10, generating a plurality of electric stimulation signals, and stimulating different brain areas in the brain based on the electric stimulation signals, wherein a preset phase difference exists between the electric stimulation signals;
s20, after the brain is stimulated by the electrical stimulation signals for a preset time, acquiring brain electrical signals of the brain;
and S30, evaluating the electroencephalogram signals and adjusting the electric stimulation signals based on the evaluation result.
As an example, the closed-loop feedback transcranial alternating current stimulation method in the present embodiment may be performed based on a closed-loop feedback transcranial alternating current stimulation system as in fig. 1-3.
After step S30, that is, after the electrical stimulation signal is adjusted based on the evaluation result, the method may further include repeating the above steps (that is, steps S10 to S30) at least once, where the generated multiple electrical stimulation signals are all electrical stimulation signals adjusted based on the evaluation result of the previous step.
As an example, in step S10, the generating a plurality of electrical stimulation signals may include the following steps:
s101, setting parameters for generating a voltage waveform signal, wherein the setting parameters comprise peak current for generating the voltage waveform signal, waveform mode of the voltage waveform signal, frequency of the voltage waveform signal, phase difference of different voltage waveform signals and duration time of the voltage waveform signal;
s102, generating a voltage waveform signal based on the setting parameters;
And S103, generating the electric stimulation signal based on the voltage waveform signal.
As an example, in step S10, the duration of one stimulation of different brain regions in the brain based on the electrical stimulation signal may be 5 seconds.
As an example, the interval time between step S10 and step S20 may be 15 seconds. In step S20, the duration of one time of acquiring brain electrical signals of the brain may be 30 seconds.
As an example, the brain electrical signals include a first brain electrical signal of a first brain region and a second brain electrical signal of a second brain region; in step S30, the evaluating the electroencephalogram signal and adjusting the electrical stimulation signal based on the evaluation result may include the following steps:
S301, preprocessing and band-pass filtering are carried out on the electroencephalogram signals to obtain nerve oscillation signals, wherein the nerve oscillation signals comprise first nerve oscillation signals corresponding to the first electroencephalogram signals and second nerve oscillation signals corresponding to the second electroencephalogram signals;
S302, carrying out Hilbert transformation on the nerve oscillation signal to obtain instant phase information, wherein the instant phase information comprises a first instant phase and a second instant phase;
S303, processing the phase information to obtain a phase difference between the first electroencephalogram signal and the second electroencephalogram signal;
s304, comparing and evaluating the phase difference with a target phase difference to obtain an evaluation result;
and S305, adjusting the electric stimulation signal based on the evaluation result.
As an example, in step S302, the neural oscillation signal is Hilbert transformed based on the following formula to obtain the instantaneous phase information:
Wherein, Is the first instantaneous phase; Is a second instant phase, x 1 (t) is a first nerve oscillation signal at the moment of t of a first brain region, x 2 (t) is a second nerve oscillation signal at the moment of t of a second brain region, P and V are cauchy main values, tau is an integral variable, x 1 (tau) is a nerve oscillation signal of the integral variable tau corresponding to the first brain region, and x 2 (tau) is a nerve oscillation signal of the integral variable tau corresponding to the second brain region.
As an example, in step S303, the phase information is processed based on the following formula to obtain a phase difference between the first electroencephalogram signal and the second electroencephalogram signal:
Wherein, A phase difference between the first electroencephalogram signal and the second electroencephalogram signal; an instantaneous phase of a first neural oscillating signal at a time t n for the first brain region; The method comprises the steps of obtaining a first brain region, obtaining a first nerve oscillation signal of the first brain region, obtaining a second brain region, obtaining a first brain signal of the first brain region, obtaining a second brain signal of the second brain region, obtaining an instant phase of the second nerve oscillation signal of the second brain region at a time t n, wherein n=1, 2.
As an example, in step S305, the adjusting the electrical stimulation signal based on the evaluation result includes adjusting to decrease the stimulation time of the electrical stimulation signal and decrease the stimulation intensity of the electrical stimulation signal if the difference between the phase difference and the target phase difference is smaller than a preset phase, and adjusting to increase the stimulation time of the electrical stimulation signal and increase the stimulation intensity of the electrical stimulation signal if the difference between the phase difference and the target phase difference is greater than or equal to a preset phase.
For example, referring to FIG. 5, the closed-loop feedback transcranial AC stimulation method of the present application may be as follows, the current intensity of the electrical stimulation signal is A, and the phase difference isThe first brain region (i.e., brain region 1) and the second brain region (i.e., brain region 2) are electrically stimulated, which may be 5 seconds in duration. After an electrical stimulation interval of 10 seconds, the brain electrical signals of each brain region (i.e. the original brain electrical signals of brain region 1 and brain region 2) are recorded. Preprocessing the recorded electroencephalogram signals, and carrying out band-pass filtering processing to obtain nerve oscillation signals with specified frequency bands. Deriving instantaneous phase information using a Hilbert transform, the instantaneous phase information comprising a first instantaneous phase informationAnd a second instant phaseSolving to obtain a phase difference based on the following formula:
Wherein, A phase difference between the first electroencephalogram signal and the second electroencephalogram signal; an instantaneous phase of a first neural oscillating signal at a time t n for the first brain region; The method comprises the steps of obtaining a first brain region, obtaining a first nerve oscillation signal of the first brain region, obtaining a second brain region, obtaining a first brain signal of the first brain region, obtaining a second brain signal of the second brain region, obtaining an instant phase of the second nerve oscillation signal of the second brain region at a time t n, wherein n=1, 2. The phase difference is compared with a target phase difference A comparison is made. If the phase differencePhase difference from the targetThe difference of (2) is smaller than the preset phaseThe stimulation time of the electric stimulation signal is reduced, the stimulation intensity of the electric stimulation signal is reduced, the stimulation time can be reduced by 1 second, the stimulation intensity is reduced by 20%, and if the phase difference is the phase differencePhase difference from the targetThe difference of (2) is greater than or equal to the preset phaseThe stimulation time of the electric stimulation signal is adjusted to be increased, and the stimulation intensity of the electric stimulation signal is enhanced, specifically, the stimulation time is increased by 1 second, and the stimulation intensity is enhanced by 20%. Preset phaseMay be 0.1 deg., i.e., about 0.174532 deg..
As an example, referring to fig. 5, after the electric stimulation signal is adjusted, the method may further include the step of determining whether the current intensity a of the adjusted electric stimulation signal is 0 or whether the current intensity a is greater than a safety threshold, if so, stopping electric stimulation, and if not, electrically stimulating different brain regions based on the adjusted electric stimulation signal.
The closed-loop feedback transcranial alternating current stimulation system and method of the application can have the following beneficial effects:
1) The brain region is subjected to compound stimulation through cross-brain region and multi-frequency band coupling, and different functions of nerve regulation and control are simultaneously carried out through a plurality of output electrodes, so that the nerve activity of the brain region is monitored in real time by combining a closed loop feedback system, and a nerve regulation mechanism and an effective plastic nerve path related to movement, cognition, learning, memory and the like can be further improved, thereby helping healthy old people and dysfunctional people to improve the movement, the memory and the cognitive ability;
2) The brain function network is dynamically changed, the roles and the correlations of the areas in the network are changed along with the functions, and the phase difference of the neural oscillation coupling can reveal complex phase difference interaction and information transmission mechanisms between the brains. Based on the specific phase relation of brain regions with different functions, two paths of waveforms are adopted, an independent phase stimulation system 10 is adopted, the independent adjustment of parameters such as waveforms and the like is convenient, the neural activity of the brain region 40 to be tested is monitored in real time by combining with the evaluation feedback system 30, and the beginning and the end of stimulation are automatically adjusted according to feedback information. By flexibly adjusting the phase difference parameters of different brain regions, more accurate stimulation of tACS is realized, and the functions are more effectively improved. For example, by applying theta wave stimulation at different phases to the frontal cortex and hippocampus, the neural oscillating coupling between the two brain regions can be modulated, thereby improving cognitive dysfunction or impairment.
The closed-loop feedback transcranial alternating current stimulation system provided by the application is expected to play an important role in the treatment of cognitive dysfunction diseases such as Alzheimer's disease, craniocerebral injury and cerebral apoplexy by virtue of high personalized customization capability, accurate nerve regulation and control effect and perfect safety guarantee measures. In addition, the method can be used in the fields of brain function optimization in athlete training, cognitive function improvement of healthy elderly people and the like, contributes important strength to improving the overall health level of human beings, and has wide application prospect and social value.
The technical features of the above embodiments may be arbitrarily combined, and for brevity of description, all possible combinations of the technical features of the above embodiments are not described, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope described in the present specification.
The foregoing examples illustrate only a few embodiments of the application, which are described in detail and are not to be construed as limiting the scope of the claims. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the application, which are all within the scope of the application. Accordingly, the scope of protection of the present application is to be determined by the appended claims.
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