Closed-loop feedback transcranial alternating current stimulation system and method

Abstract

The invention relates to a closed-loop feedback transcranial alternating current stimulation system and method. The closed-loop feedback transcranial alternating current stimulation system comprises a phase stimulation system used for generating a plurality of electrical stimulation signals and stimulating different brain areas in the brain based on the electrical stimulation signals; a preset phase difference exists between the electrical stimulation signals; the electroencephalogram acquisition system is used for acquiring electroencephalogram 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 electrical stimulation signals based on an evaluation result. According to the closed-loop feedback transcranial alternating current stimulation system, the waveform signal can be flexibly adjusted based on the real-time oscillation signal of the brain, and the problems that in the prior art, the shock wave form is single, individual differences cannot be accurately matched, and dynamic brain network state changes cannot be adapted are solved.

Description

Technical Field

[0001] The present application relates to the field of medical equipment technology, and in particular to a closed-loop feedback transcranial alternating current stimulation system and method. Background Art

[0002] Transcranial alternating current stimulation (tACS) is a non-invasive and effective treatment for regulating brain cognitive function. There are various tACS stimulation methods. For example, cognitive dysfunction and cognitive impairment are particularly common in patients with Alzheimer's disease (AD), traumatic brain injury (TBI) and stroke. tACS directly interferes with the ongoing oscillation activity of the brain by applying sinusoidal current to the intact scalp, which is expected to improve cognitive dysfunction or cognitive impairment. At present, tACS still has some shortcomings and limitations, especially in the application of multi-brain region stimulation, there are problems such as single stimulation waveform, difficulty in accurately matching individual differences, and inability to adapt to changes in dynamic brain network states. Summary of the invention

[0003] Based on this, it is necessary to provide a closed-loop feedback transcranial alternating current stimulation system and method to address the problems in the related technology.

[0004] In order to achieve the above objectives, in a first aspect, the present application provides a closed-loop feedback transcranial alternating current stimulation system, the closed-loop feedback transcranial alternating current stimulation system comprising:

[0005] A phase stimulation system, for generating a plurality of electrical stimulation signals, and stimulating different brain regions in the brain based on the electrical stimulation signals; each of the electrical stimulation signals has a preset phase difference;

[0006] An electroencephalogram (EEG) acquisition system, used to acquire EEG signals of the brain after the phase stimulation system stimulates the brain for a preset time;

[0007] The evaluation feedback system is connected to both the phase stimulation system and the EEG acquisition system, and is used to evaluate the EEG signals acquired by the EEG acquisition system and adjust the electrical stimulation signals based on the evaluation results.

[0008] In some embodiments, the phasic stimulation system comprises:

[0009] A parameter input device, used to set the setting parameters for generating the voltage waveform signal, the setting parameters including: the peak current for generating the voltage waveform signal, the waveform mode of the voltage waveform signal, the frequency of the voltage waveform signal, the phase difference between different voltage waveform signals and the duration of the voltage waveform signal;

[0010] A voltage-controlled waveform generating device, connected to the parameter input device, for generating a voltage waveform signal based on the setting parameters;

[0011] A Howland constant current source, connected to the voltage-controlled waveform generating device, for generating the electrical stimulation signal based on the voltage waveform signal;

[0012] The electrical stimulation signal output device is connected to the Howland constant current source and is used to stimulate different brain regions in the brain based on the electrical stimulation signal.

[0013] In some embodiments, the phasic stimulation system further comprises:

[0014] The waveform measuring device is connected to the voltage-controlled waveform generating device and the electrical stimulation signal output device, and is used to sample and detect the voltage waveform signal, and when the detection result is abnormal, control the electrical stimulation signal output device to stop outputting the electrical stimulation signal.

[0015] In some embodiments, the electrical stimulation signal output device includes a brain nail, and the EEG acquisition system includes the brain nail and the EEG signal collection device; the closed-loop feedback transcranial alternating current stimulation system also includes:

[0016] A single-pole double-throw relay is connected to the brain nail, the electroencephalogram signal collection device and the Howland constant current source.

[0017] In some embodiments, the EEG signal includes a first EEG signal of a first brain region and a second EEG signal of a second brain region; and the evaluation feedback system includes:

[0018] A preprocessing module, connected to the EEG acquisition system, for preprocessing and bandpass filtering the EEG signal to obtain a neural oscillation signal; the neural oscillation signal includes a first neural oscillation signal corresponding to the first EEG signal and a second neural oscillation signal corresponding to the second EEG signal;

[0019] A transformation module, connected to the preprocessing module, for performing Hilbert transformation on the neural oscillation signal to obtain instantaneous phase information, wherein the instantaneous phase information includes a first instantaneous phase and a second instantaneous phase;

[0020] a processing module, connected to the transformation module, and configured to obtain a phase difference between the first EEG signal and the second EEG signal based on the instantaneous phase information;

[0021] A judgment module, connected to the processing module, for comparing and evaluating the phase difference with a target phase difference to obtain an evaluation result;

[0022] A parameter adjustment module is connected to the judgment module and is used to adjust the electrical stimulation signal based on the evaluation result.

[0023] In a second aspect, the present application further provides a closed-loop feedback transcranial alternating current stimulation method, the closed-loop feedback transcranial alternating current stimulation method comprising:

[0024] Generate multiple electrical stimulation signals, and stimulate different brain regions in the brain based on the electrical stimulation signals; each of the electrical stimulation signals has a preset phase difference;

[0025] After the electrical stimulation signal stimulates the brain for a preset time, collecting an electroencephalogram signal of the brain;

[0026] The electroencephalogram signal is evaluated, and the electrical stimulation signal is adjusted based on the evaluation result.

[0027] In some of the embodiments, after adjusting the electrical stimulation signal based on the evaluation result, the method further includes: repeating the above steps at least once; in the repeated steps, the multiple electrical stimulation signals generated are all electrical stimulation signals adjusted based on the evaluation result of the previous step.

[0028] In some embodiments, the generating of multiple electrical stimulation signals comprises:

[0029] Setting parameters for generating a voltage waveform signal, the setting parameters including: a peak current for generating the voltage waveform signal, a waveform mode of the voltage waveform signal, a frequency of the voltage waveform signal, a phase difference between different voltage waveform signals, and a duration of the voltage waveform signal;

[0030] generating a voltage waveform signal based on the setting parameters;

[0031] The electrical stimulation signal is generated based on the voltage waveform signal.

[0032] In some embodiments, the EEG signal includes a first EEG signal of a first brain region and a second EEG signal of a second brain region; and the evaluating the EEG signal and adjusting the electrical stimulation signal based on the evaluation result include:

[0033] Preprocessing and bandpass filtering the EEG signal to obtain a neural oscillation signal; the neural oscillation signal includes a first neural oscillation signal corresponding to the first EEG signal and a second neural oscillation signal corresponding to the second EEG signal;

[0034] Performing Hilbert transformation on the neural oscillation signal to obtain instantaneous phase information, wherein the instantaneous phase information includes a first instantaneous phase and a second instantaneous phase;

[0035] Processing the phase information to obtain a phase difference between the first EEG signal and the second EEG signal;

[0036] Comparing and evaluating the phase difference with a target phase difference to obtain an evaluation result;

[0037] The electrical stimulation signal is adjusted based on the evaluation result.

[0038] In one embodiment, the neural oscillation signal is subjected to Hilbert transformation based on the following formula to obtain instantaneous phase information:

[0039]

[0040] in, It is the first instantaneous phase; is the second instantaneous phase; x 1 (t) is the first neural oscillation signal of the first brain region at time t; x 2 (t) is the second neural oscillation signal of the second brain area at time t; P and V are the Cauchy principal values; τ is the integral variable; x 1 (t) is the neural oscillation signal of the first brain area corresponding to the integral variable τ; x 2 (τ) is the neural oscillation signal of the second brain area corresponding to the integral variable τ;

[0041] The phase information is processed based on the following formula to obtain the phase difference between the first EEG signal and the second EEG signal:

[0042]

[0043] in, is the phase difference between the first EEG signal and the second EEG signal; The first brain area at t n The instantaneous phase of the first neural oscillation signal at the moment; The second brain area is nThe instantaneous phase of the second neural oscillation signal at the moment; n = 1, 2 ... N, N is the total length of the data samples of the first EEG signal and the second EEG signal recorded after stimulation; the horizontal line at the top of the expression to the right of the equal sign in the formula represents averaging.

[0044] The adjusting of the electrical stimulation signal based on the evaluation result includes: if the difference between the phase difference and the target phase difference is less than a preset phase, adjusting to reduce the stimulation time of the electrical stimulation signal and reducing 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 the preset phase, adjusting to increase the stimulation time of the electrical stimulation signal and enhancing the stimulation intensity of the electrical stimulation signal.

[0045] In the above-mentioned closed-loop feedback transcranial alternating current stimulation system and method, by setting the phase stimulation system, the EEG acquisition system and the evaluation feedback system, the phase stimulation system can generate an electrical stimulation signal with a preset phase difference, can achieve coupling of cross-brain region and multi-channel neural oscillations, and can flexibly adjust the electrical stimulation signal based on the real-time EEG signal of the brain, thereby solving the problems existing in the prior art such as the single stimulation waveform, difficulty in accurately matching individual differences, and inability to adapt to changes in dynamic brain network states. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the conventional technology, the drawings required for use in the embodiments or the conventional technology descriptions are briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0047] Figure 1 It is a structural block diagram of a closed-loop feedback transcranial alternating current stimulation system provided in one embodiment of the present application;

[0048] Figure 2 It is a structural block diagram of a phase stimulation system in a closed-loop feedback transcranial alternating current stimulation system provided in one embodiment of the present application;

[0049] Figure 3 It is a structural block diagram of an evaluation feedback system in a closed-loop feedback transcranial alternating current stimulation system provided in one embodiment of the present application;

[0050] Figure 4 and Figure 5 This is a flow chart of a closed-loop feedback transcranial alternating current stimulation method provided in another embodiment of the present application.

[0051] Explanation of the accompanying drawings: 10, phase stimulation system; 101, parameter input device; 102, voltage-controlled waveform generating device; 103, Howland constant current source; 104, electrical stimulation signal output device; 20, EEG acquisition system; 30, evaluation feedback system; 301, preprocessing module; 302, transformation module; 303, processing module; 304, judgment module; 305, parameter adjustment module; 40, test brain area. DETAILED DESCRIPTION

[0052] In order to make the purpose, technical solution and advantages of the present application more clearly understood, the present application is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present application and are not used to limit the present application.

[0053] Transcranial alternating current stimulation (tACS) is a non-invasive and effective treatment for regulating brain cognitive function. There are various tACS stimulation methods available. For example, cognitive dysfunction and cognitive impairment are particularly common in patients with Alzheimer's disease (AD), traumatic brain injury (TBI), and stroke. tACS directly interferes with the ongoing oscillatory activity of the brain by applying sinusoidal current to the intact scalp, which is expected to improve cognitive dysfunction or cognitive impairment. tACS still has some shortcomings and limitations, especially in the application of multi-brain region stimulation. Due to the complexity of designing individualized stimulation schemes for multiple brain regions, different functions and neural circuits need to be considered. Although high-precision and high-intensity tACS schemes already exist, there is still a lack of regulation schemes for coordinated activity patterns between brain regions based on different tasks (such as movement, memory, decision-making, etc.).

[0054] Neural oscillatory coupling refers to the synchronous activity between different neuronal populations in the brain, which is usually manifested as an oscillation pattern of a specific frequency. In high-level cognitive functions such as attention, memory encoding, and information transfer, neuronal populations in different brain regions oscillate at the same frequency, and their phase relationship is usually expressed as a stable coupling relationship with a fixed phase difference. Neural oscillatory coupling phase difference refers to the phase relationship between two or more neural oscillators, which is of great significance in neuroscience. It can reflect the degree of synchronization between different neuronal populations or brain regions and reveal the direction of information transfer. Phase coupling differences in different frequency ranges may be associated with different neural functions. For example, the phase coupling of gamma waves may be associated with perception and attention, while the phase coupling of theta waves may be associated with memory and navigation. Specific phase relationships may also be associated with specific cognitive or behavioral states, indicating the coordinated activity of specific brain regions in certain tasks or states. At present, there is no transcranial alternating current stimulation system based on phase difference. For example, during working memory, the coupling between the prefrontal cortex (PFC) and the hippocampus (HPC) is mainly manifested as the theta frequency phase coupling of the PFC and HPC waves.

[0055] In one embodiment, see Figure 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, wherein the phase stimulation system 10 is used to generate a plurality of electrical stimulation signals, and stimulate different brain regions in the brain based on the electrical stimulation signals; each of the electrical stimulation signals has a preset phase difference; the electroencephalogram acquisition system 20 is used to stimulate the brain (i.e., Figure 1 After stimulating the test brain area 40) for a preset time, the EEG signal of the brain is collected; the evaluation feedback system 30 is connected to the phase stimulation system 10 and the EEG acquisition system 20, and is used to evaluate the EEG signal collected by the EEG acquisition system 20, and adjust the electrical stimulation signal based on the evaluation result.

[0056] In the above-mentioned closed-loop feedback transcranial alternating current stimulation system, by setting the phase stimulation system 10, the EEG acquisition system 20 and the evaluation feedback system 30, the phase stimulation system 10 can generate an electrical stimulation signal with a preset phase difference, can achieve the coupling of cross-brain region and multi-channel neural oscillations, and can flexibly adjust the electrical stimulation signal based on the real-time EEG signal of the brain, thereby solving the problems existing in the prior art such as the single stimulation waveform, difficulty in accurately matching individual differences, and inability to adapt to changes in dynamic brain network states.

[0057] As an example, see Figure 2 The phase stimulation system may include: a parameter input device 101, a voltage-controlled waveform generating device 102, a Howland constant current source 103 and an electrical stimulation signal output device 104; wherein the parameter input device 101 is used to set the setting parameters for generating a voltage waveform signal, and the setting parameters include: the peak current for generating the voltage waveform signal, the waveform mode of the voltage waveform signal, the frequency of the voltage waveform signal, the phase difference between different voltage waveform signals and the duration of the voltage waveform signal; the voltage-controlled waveform generating device 102 is connected to the parameter input device 101, and is used to generate a voltage waveform signal based on the setting parameters; the Howland constant current source 103 is connected to the voltage-controlled waveform generating device 102, and is used to generate the electrical stimulation signal based on the voltage waveform signal; the electrical stimulation signal output device 104 is connected to the Howland constant current source 103, and is used to stimulate different brain regions in the brain based on the electrical stimulation signal.

[0058] As an example, the parameter input device 101 is used to set the peak current used to generate the voltage waveform signal, the waveform of the voltage waveform signal (including but not limited to sine wave, square wave, triangle wave and mixed waveforms thereof), the frequency of the voltage waveform signal, the phase difference between different voltage waveform signals and the duration of the voltage waveform signal.

[0059] Specifically, the frequency of each voltage waveform signal can be freely adjusted within the specified frequency band, such as the voltage waveform signal can be adjusted to produce the following oscillations: delta oscillation (frequency is 0.5-4Hz), theta oscillation (4-8Hz), alpha oscillation (8-12Hz), beta oscillation (13-30Hz) and low-frequency and high-frequency gamma oscillation (30-150Hz, where the low frequency is 30-70Hz and the high frequency is 70-150Hz) to match different brain regions, different neural oscillation patterns and specific phase difference requirements. This high sensitivity allows the closed-loop feedback transcranial alternating current stimulation system of the present application to be customized according to the patient's specific neurological dysfunction type, degree and brain network state, which can significantly improve the treatment effect.

[0060] The phase stimulation system 10 of the present application can apply electrical stimulation signals corresponding to functional rhythms in specific brain regions, and can trigger or adjust specific neural activity rhythms in specific brain regions as needed to simulate or enhance natural brain wave patterns, thereby achieving regulation or optimization of brain functions. The waveform signals of these rhythms usually correspond to various cognitive or physiological states of the brain, such as concentration, relaxation, sleep, or memory processing, and can accurately match the physiological characteristics and needs of the target brain region, thereby effectively supporting the performance and improvement of related functions.

[0061] As an example, the voltage-controlled waveform generating device 102 can 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 device 101.

[0062] As an example, the Howland constant current source 103 can obtain the electrical stimulation signal based on the voltage waveform signal according to the calculation formula of the Howland model and the proportional relationship between current and voltage. The electrical stimulation signal can be a current signal.

[0063] As an example, the electrical stimulation signal output device 104 may include but is not limited to brain pins (not shown) or electrodes (not shown); in this embodiment, the electrical stimulation signal output device 104 may include brain pins, and the number of the brain pins may be multiple, and each of the brain pins is respectively arranged in a different brain area.

[0064] As an example, the phase stimulation system may further include: a waveform measuring device (not shown), the waveform measuring device is connected to the voltage-controlled waveform generating device 102 and the electrical stimulation signal output device 104, the waveform measuring device is used to sample and detect the voltage waveform signal, and when the detection result is abnormal, control the electrical stimulation signal output device 104 to stop outputting the electrical stimulation signal. By judging the quality of the voltage waveform signal generated by the voltage-controlled waveform generating device 102 in real time through the waveform measuring device, it is possible to judge whether an abnormality occurs in the electrical stimulation output device 104 (for example, whether the electrical stimulation output device falls off, etc.).

[0065] As an example, the EEG acquisition system may include the brain nail and the EEG signal collection device (not shown); the closed-loop feedback transcranial alternating current stimulation system may also include: a single-pole double-throw relay (not shown), the single-pole double-throw relay is connected to the brain nail, the EEG signal collection device and the Howland constant current source 103. That is, in this embodiment, the EEG acquisition system 20 and the phase stimulation system 10 share the brain nail, that is, the electrical stimulation output device 104 of the phase stimulation system 10 and the collection device of the EEG acquisition system 20 for collecting EEG signals are the same device. However, due to the huge difference between the signals of the phase stimulation system 10 and the EEG acquisition system 20, it is necessary to protect the closed-loop feedback transcranial alternating current stimulation system and ensure that the electrical stimulation part has no effect on EEG acquisition. Based on this, by setting the single-pole double-throw relay, when the phase stimulation system 10 electrically stimulates the brain area, the EEG acquisition system 20 can be disconnected from collecting EEG signals, and when the EEG stimulation system 20 collects EEG signals, the phase stimulation system 10 can be disconnected from electrically stimulating the brain area, so as to ensure the accuracy of the EEG signals collected by the EEG acquisition system 20 and ensure safety.

[0066] As an example, the EEG signal includes a first EEG signal of a first brain region and a second EEG signal of a second brain region; the evaluation feedback system 30 may include: a preprocessing module 301, a transformation module 302, a processing module 303, a judgment module 304 and a parameter adjustment module 305; wherein the preprocessing module 301 is connected to the EEG acquisition system 20, and is used to preprocess and bandpass filter the EEG signal to obtain a neural oscillation signal; the neural oscillation signal includes a first neural oscillation signal corresponding to the first EEG signal and a second neural oscillation signal corresponding to the second EEG signal; the transformation module 302 is connected to the preprocessing module 301, and the processing module 303 is connected to the preprocessing module 304, and the processing module 305 is connected to the preprocessing module 301. The module 301 is connected to perform Hilbert transform on the neural oscillation signal to obtain instantaneous phase information, wherein the instantaneous phase information includes a first instantaneous phase and a second instantaneous phase; the processing module 303 is connected to the transformation module 302, and is used to obtain the phase difference between the first EEG signal and the second EEG signal based on the instantaneous phase information; the judgment module 304 is connected to the processing module 303, and is used to compare and evaluate the phase difference with the target phase difference to obtain an evaluation result; the parameter adjustment module 305 is connected to the judgment module 304, and is used to adjust the electrical stimulation signal based on the evaluation result.

[0067] As an example, the transformation 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:

[0068]

[0069] in, It is the first instantaneous phase; is the second instantaneous phase; x 1 (t) is the first neural oscillation signal of the first brain region at time t; x 2 (t) is the second neural oscillation signal of the second brain area at time t; P and V are the Cauchy principal values; τ is the integral variable; x 1 (τ) is the neural oscillation signal of the first brain area corresponding to the integral variable τ; x 2 (τ) is the neural oscillation signal of the second brain area corresponding to the integral variable τ.

[0070] As an example, the processing module 303 obtains the phase difference between the first EEG signal and the second EEG signal based on the following formula:

[0071]

[0072] in, is the phase difference between the first EEG signal and the second EEG signal; The first brain area at t n The instantaneous phase of the first neural oscillation signal at the moment; The second brain area is n The instantaneous phase of the second neural oscillation signal at the moment; n = 1, 2 ... N, N is the total length of the data samples of the first EEG signal and the second EEG signal recorded after stimulation; the horizontal line at the top of the expression to the right of the equal sign in the formula represents averaging.

[0073] As an example, the specific method for the parameter adjustment module 305 to adjust the electrical stimulation signal based on the evaluation result is: if the difference between the phase difference and the target phase difference is less than the preset phase, then the stimulation time of the electrical stimulation signal is reduced, and the stimulation intensity of the electrical stimulation signal is reduced; if the difference between the phase difference and the target phase difference is greater than or equal to the preset phase, then the stimulation time of the electrical stimulation signal is increased, and the stimulation intensity of the electrical stimulation signal is enhanced.

[0074] As an example, the closed-loop feedback transcranial alternating current stimulation system may further include a safety module (not shown), which is connected to the parameter adjustment module 305 and the phase stimulation system 10. The safety module is used to determine whether the current intensity of the electrical stimulation signal after the electrical stimulation signal is adjusted by the parameter adjustment module 305 is 0 or whether the current intensity is greater than a safety threshold. If so, the electrical stimulation is stopped; if not, electrical stimulation is performed on different brain regions based on the adjusted electrical stimulation signal.

[0075] In a specific example, a small mouse can be subjected to a craniotomy and four brain pins can be implanted in its brain. The four brain pins can be arranged according to a preset arrangement rule; the evaluation feedback system 30 is a software running on a PC. The evaluation feedback system 30 is connected to the phase stimulation system 10 via a USB CDC or a serial port. The evaluation feedback system 30 requires the phase stimulation system 10 to generate two sinusoidal current signals with a maximum peak current of 5ma, and the phase difference between the two signals is 90 degrees. The phase stimulation system 10 generates two sinusoidal output tables according to the above parameters; the phase difference of the output table is 90 degrees. The voltage-controlled waveform generating device 102 uses a DAC circuit to convert the output table into a sinusoidal voltage signal. Using the Howland constant current source, for example, using TI's power operational amplifier, such as OPA462, OPA455, OPA445, OPA452, combined with a high-voltage positive and negative power supply, such as +-75V, a circuit waveform (i.e., the electrical stimulation signal) is generated. The reason for using such high voltage is that electrical stimulation is a kind of current stimulation, and the impedance between the two stimulation electrodes will change. According to the size of the impedance, the peak voltage required can be calculated.

[0076] As an example, the phase stimulation system 10 may be used for 5 seconds for one stimulation, the interval between stimulation and EEG signal acquisition, i.e. the preset time, may be 15 seconds, and the time for continuous acquisition of EEG signals from the subject brain area 40 may be 30 seconds.

[0077] In another embodiment, please combine Figures 1 to 3 See also Figure 4 The present application also provides a closed-loop feedback transcranial alternating current stimulation method, which may include the following steps:

[0078] S10: generating a plurality of electrical stimulation signals, and stimulating different brain regions in the brain based on the electrical stimulation signals; each of the electrical stimulation signals has a preset phase difference;

[0079] S20: After the electrical stimulation signal stimulates the brain for a preset time, collecting an electroencephalogram signal of the brain;

[0080] S30: Evaluate the EEG signal, and adjust the electrical stimulation signal based on the evaluation result.

[0081] As an example, the closed-loop feedback transcranial alternating current stimulation method in this embodiment can be based on Figures 1 to 3 This is performed using a closed-loop feedback transcranial alternating current stimulation system.

[0082] As an example, after step S30, that is, after adjusting the electrical stimulation signal based on the evaluation result, it can also include: repeating the above steps (that is, steps S10 to S30) at least once; in the repeated steps, the multiple electrical stimulation signals generated are all electrical stimulation signals adjusted based on the evaluation result of the previous step.

[0083] As an example, in step S10, generating a plurality of electrical stimulation signals may include the following steps:

[0084] S101: Setting parameters for generating a voltage waveform signal, the setting parameters including: a peak current for generating the voltage waveform signal, a waveform mode of the voltage waveform signal, a frequency of the voltage waveform signal, a phase difference between different voltage waveform signals, and a duration of the voltage waveform signal;

[0085] S102: generating a voltage waveform signal based on the setting parameters;

[0086] S103: Generate the electrical stimulation signal based on the voltage waveform signal.

[0087] As an example, in step S10, the duration of stimulating different brain regions in the brain based on the electrical stimulation signal may be 5 seconds.

[0088] As an example, the interval between step S10 and step S20 may be 15 seconds. In step S20, the duration of collecting the brain electroencephalogram signal once may be 30 seconds.

[0089] As an example, the EEG signal includes a first EEG signal of a first brain region and a second EEG signal of a second brain region; in step S30, evaluating the EEG signal and adjusting the electrical stimulation signal based on the evaluation result may include the following steps:

[0090] S301: preprocessing and bandpass filtering the EEG signal to obtain a neural oscillation signal; the neural oscillation signal includes a first neural oscillation signal corresponding to the first EEG signal and a second neural oscillation signal corresponding to the second EEG signal;

[0091] S302: performing Hilbert transform on the neural oscillation signal to obtain instantaneous phase information, wherein the instantaneous phase information includes a first instantaneous phase and a second instantaneous phase;

[0092] S303: Processing the phase information to obtain a phase difference between the first EEG signal and the second EEG signal;

[0093] S304: Compare and evaluate the phase difference with the target phase difference to obtain an evaluation result;

[0094] S305: Adjust the electrical stimulation signal based on the evaluation result.

[0095] As an example, in step S302, the neural oscillation signal is subjected to Hilbert transformation based on the following formula to obtain instantaneous phase information:

[0096]

[0097] in, It is the first instantaneous phase; is the second instantaneous phase; x 1 (t) is the first neural oscillation signal of the first brain region at time t; x 2 (t) is the second neural oscillation signal of the second brain area at time t; P and V are the Cauchy principal values; τ is the integral variable; x 1 (τ) is the neural oscillation signal of the first brain area corresponding to the integral variable τ; x 2 (τ) is the neural oscillation signal of the second brain area corresponding to the integral variable τ.

[0098] As an example, in step S303, the phase information is processed based on the following formula to obtain the phase difference between the first EEG signal and the second EEG signal:

[0099]

[0100] in, is the phase difference between the first EEG signal and the second EEG signal; The first brain area at t n The instantaneous phase of the first neural oscillation signal at the moment; The second brain area is n The instantaneous phase of the second neural oscillation signal at the moment; n = 1, 2 ... N, N is the total length of the data samples of the first EEG signal and the second EEG signal recorded after stimulation; the horizontal line at the top of the expression to the right of the equal sign in the formula represents averaging.

[0101] As an example, in step S305, the electrical stimulation signal is adjusted based on the evaluation result, including: if the difference between the phase difference and the target phase difference is less than a preset phase, then the stimulation time of the electrical stimulation signal is reduced, and the stimulation intensity of the electrical stimulation signal is reduced; if the difference between the phase difference and the target phase difference is greater than or equal to the preset phase, then the stimulation time of the electrical stimulation signal is increased, and the stimulation intensity of the electrical stimulation signal is enhanced.

[0102] As an example, see Figure 5The closed-loop feedback transcranial alternating current stimulation method of the present application can be as follows: the current intensity of the electrical stimulation signal is A, and the phase difference is The first brain region (i.e., brain region 1) and the second brain region (i.e., brain region 2) are electrically stimulated, and the duration of the electrical stimulation may be 5 seconds. The EEG signals of each brain region are recorded after a 10-second interval of electrical stimulation (i.e., the original EEG signals of brain region 1 and the original EEG signals of brain region 2 are recorded). The recorded EEG signals are preprocessed and bandpass filtered to obtain a neural oscillation signal of a specified frequency band. The instantaneous phase information is obtained using Hilbert transform, and the instantaneous phase information includes the first instantaneous and the second instant phase The phase difference is obtained based on the following formula:

[0103]

[0104] in, is the phase difference between the first EEG signal and the second EEG signal; The first brain area at t n The instantaneous phase of the first neural oscillation signal at the moment; The second brain area is n The instantaneous phase of the second neural oscillation signal at the moment; n = 1, 2 ... N, N is the total length of the data samples of the first EEG signal and the second EEG signal recorded after stimulation; the horizontal line at the top of the expression on the right side of the equal sign in the formula represents the average. If the phase difference The phase difference with the target The difference is less than the preset phase Then the stimulation time of the electrical stimulation signal is reduced, and the stimulation intensity of the electrical stimulation signal is reduced. Specifically, the stimulation time can be reduced by 1 second and the stimulation intensity can be reduced by 20%. If the phase difference The phase difference with the target The difference is greater than or equal to the preset phase The stimulation time of the electrical stimulation signal is adjusted and increased, and the stimulation intensity of the electrical stimulation signal is enhanced. Specifically, the stimulation time can be increased by 1 second and the stimulation intensity can be increased by 20%. It can be 0.1°, which is about 0.174532.

[0105] As an example, see Figure 5 After adjusting the electrical stimulation signal, the following steps may also be included: whether the current intensity A of the adjusted electrical stimulation signal is 0 or whether the current intensity A is greater than a safety threshold, if so, stop the electrical stimulation, if not, perform electrical stimulation on different brain regions based on the adjusted electrical stimulation signal.

[0106] The closed-loop feedback transcranial alternating current stimulation system and method of the present application can have the following beneficial effects:

[0107] 1) Through the formation of composite stimulation through cross-brain region and multi-band coupling, and the simultaneous neural regulation of different functions through multiple output electrodes, combined with the closed-loop feedback system to monitor the neural activity of the brain region in real time, it can further enhance the neural regulation mechanism and effective plastic neural pathways related to movement, cognition, learning, memory, etc., thereby helping healthy elderly people and people with functional disabilities to improve their movement, memory and cognitive abilities;

[0108] 2) The brain functional network is dynamically changing. The roles of the same region in the network and their mutual relationships change with function. The phase difference of neural oscillation coupling can reveal the complex phase difference, complex interaction and information transmission mechanism between brain regions. Based on the specific phase relationship of brain regions with different functions, two waveforms and an independent phase stimulation system 10 are used to facilitate independent adjustment of waveform and other parameters. Combined with the evaluation feedback system 30, the neural activity of the subject's brain region 40 is monitored in real time, and the start and end of the stimulation are automatically adjusted according to the feedback information. By flexibly adjusting the phase difference parameters of different brain regions, more accurate tACS stimulation can be achieved, so that the function can be more effectively improved. For example, by applying theta wave stimulation of different phases in the prefrontal cortex and hippocampus, the neural oscillation coupling between the two brain regions can be adjusted, thereby improving cognitive dysfunction or damage.

[0109] The closed-loop feedback transcranial alternating current stimulation system of this application is expected to play an important role in the treatment of cognitive dysfunction diseases such as Alzheimer's disease, craniocerebral injury, and stroke due to its highly personalized customization capabilities, precise neuromodulation effects, and complete safety measures. In addition, it can also be used in areas such as brain function optimization in athlete training and cognitive function improvement in healthy elderly people, making important contributions to improving the overall health level of mankind and showing broad application prospects and social value.

[0110] The technical features of the above embodiments may be combined arbitrarily. To make the description concise, not all possible combinations of the technical features of the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0111] The above embodiments only express several implementation methods of the present application, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the patent application. It should be pointed out that, for a person of ordinary skill in the art, several variations and improvements can be made without departing from the concept of the present application, and these all belong to the protection scope of the present application. Therefore, the protection scope of the patent application shall be subject to the attached claims.

Claims

1. A closed-loop feedback transcranial alternating current stimulation system, characterized in that: include: A phase stimulation system, for generating a plurality of electrical stimulation signals, and stimulating different brain regions in the brain based on the electrical stimulation signals; each of the electrical stimulation signals has a preset phase difference; An electroencephalogram (EEG) acquisition system, used to acquire EEG signals of the brain after the phase stimulation system stimulates the brain for a preset time; The evaluation feedback system is connected to both the phase stimulation system and the EEG acquisition system, and is used to evaluate the EEG signals acquired by the EEG acquisition system and adjust the electrical stimulation signals based on the evaluation results.

2. The closed-loop feedback transcranial alternating current stimulation system according to claim 1, characterized in that: The phase stimulation system comprises: A parameter input device, used to set the setting parameters for generating the voltage waveform signal, the setting parameters including: the peak current for generating the voltage waveform signal, the waveform mode of the voltage waveform signal, the frequency of the voltage waveform signal, the phase difference between different voltage waveform signals and the duration of the voltage waveform signal; A voltage-controlled waveform generating device, connected to the parameter input device, for generating a voltage waveform signal based on the setting parameters; A Howland constant current source, connected to the voltage-controlled waveform generating device, for generating the electrical stimulation signal based on the voltage waveform signal; The electrical stimulation signal output device is connected to the Howland constant current source and is used to stimulate different brain regions in the brain based on the electrical stimulation signal.

3. The closed-loop feedback transcranial alternating current stimulation system according to claim 2, characterized in that: The phasic stimulation system further comprises: The waveform measuring device is connected to the voltage-controlled waveform generating device and the electrical stimulation signal output device, and is used to sample and detect the voltage waveform signal, and when the detection result is abnormal, control the electrical stimulation signal output device to stop outputting the electrical stimulation signal.

4. The closed-loop feedback transcranial alternating current stimulation system according to claim 2, characterized in that: The electrical stimulation signal output device includes a brain spike, and the electroencephalogram acquisition system includes the brain spike and the electroencephalogram signal collection device; The closed-loop feedback transcranial alternating current stimulation system further comprises: A single-pole double-throw relay is connected to the brain nail, the electroencephalogram signal collection device and the Howland constant current source.

5. The closed-loop feedback transcranial alternating current stimulation system according to any one of claims 1 to 5, characterized in that: The EEG signal includes a first EEG signal of a first brain region and a second EEG signal of a second brain region; The evaluation feedback system includes: A preprocessing module, connected to the EEG acquisition system, for preprocessing and bandpass filtering the EEG signal to obtain a neural oscillation signal; the neural oscillation signal includes a first neural oscillation signal corresponding to the first EEG signal and a second neural oscillation signal corresponding to the second EEG signal; A transformation module, connected to the preprocessing module, for performing Hilbert transformation on the neural oscillation signal to obtain instantaneous phase information, wherein the instantaneous phase information includes a first instantaneous phase and a second instantaneous phase; a processing module, connected to the transformation module, and configured to obtain a phase difference between the first EEG signal and the second EEG signal based on the instantaneous phase information; A judgment module, connected to the processing module, for comparing and evaluating the phase difference with a target phase difference to obtain an evaluation result; A parameter adjustment module is connected to the judgment module and is used to adjust the electrical stimulation signal based on the evaluation result.

6. A closed-loop feedback transcranial alternating current stimulation method, characterized in that: include: Generate multiple electrical stimulation signals, and stimulate different brain regions in the brain based on the electrical stimulation signals; each of the electrical stimulation signals has a preset phase difference; After the electrical stimulation signal stimulates the brain for a preset time, collecting an electroencephalogram signal of the brain; The electroencephalogram signal is evaluated, and the electrical stimulation signal is adjusted based on the evaluation result.

7. The closed-loop feedback transcranial alternating current stimulation method according to claim 6, characterized in that: After adjusting the electrical stimulation signal based on the evaluation result, the method further includes: repeating the above steps at least once; in the repeated steps, the multiple electrical stimulation signals generated are all electrical stimulation signals adjusted based on the evaluation result of the previous step.

8. The closed-loop feedback transcranial alternating current stimulation method according to claim 6, characterized in that: The generating of a plurality of electrical stimulation signals comprises: Setting parameters for generating a voltage waveform signal, the setting parameters including: a peak current for generating the voltage waveform signal, a waveform mode of the voltage waveform signal, a frequency of the voltage waveform signal, a phase difference between different voltage waveform signals, and a duration of the voltage waveform signal; generating a voltage waveform signal based on the setting parameters; The electrical stimulation signal is generated based on the voltage waveform signal.

9. The closed-loop feedback transcranial alternating current stimulation method according to any one of claims 6 to 8, characterized in that: The EEG signal includes a first EEG signal of a first brain region and a second EEG signal of a second brain region; The step of evaluating the EEG signal and adjusting the electrical stimulation signal based on the evaluation result includes: Preprocessing and bandpass filtering the EEG signal to obtain a neural oscillation signal; the neural oscillation signal includes a first neural oscillation signal corresponding to the first EEG signal and a second neural oscillation signal corresponding to the second EEG signal; Performing Hilbert transformation on the neural oscillation signal to obtain instantaneous phase information, wherein the instantaneous phase information includes a first instantaneous phase and a second instantaneous phase; Processing the phase information to obtain a phase difference between the first EEG signal and the second EEG signal; Comparing and evaluating the phase difference with a target phase difference to obtain an evaluation result; The electrical stimulation signal is adjusted based on the evaluation result.

10. The closed-loop feedback transcranial alternating current stimulation method according to claim 9, characterized in that: The neural oscillation signal is subjected to Hilbert transformation based on the following formula to obtain instantaneous phase information: in, It is the first instantaneous phase; is the second instantaneous phase; x1(t) is the first neural oscillation signal of the first brain region at time t; x2(t) is the second neural oscillation signal of the second brain region at time t; P and V are the Cauchy principal values; τ is the integral variable; x1(τ) is the neural oscillation signal of the first brain region corresponding to the integral variable τ; x2(τ) is the neural oscillation signal of the second brain region corresponding to the integral variable τ; The phase information is processed based on the following formula to obtain the phase difference between the first EEG signal and the second EEG signal: in, is the phase difference between the first EEG signal and the second EEG signal; The first brain area at t n The instantaneous phase of the first neural oscillation signal at the moment; The second brain area is n The instantaneous phase of the second neural oscillation signal at the moment; n=1, 2...N, N is the total length of the data samples of the first EEG signal and the second EEG signal recorded after stimulation; The adjusting of the electrical stimulation signal based on the evaluation result includes: if the difference between the phase difference and the target phase difference is less than a preset phase, adjusting to reduce the stimulation time of the electrical stimulation signal and reducing 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 the preset phase, adjusting to increase the stimulation time of the electrical stimulation signal and enhancing the stimulation intensity of the electrical stimulation signal.

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