Cycle phase-synchronized electrical stimulation artifact removal method and system

Abstract

The application provides a method and system for removing stimulation artifact based on periodic phase synchronization, comprising: electrically stimulating a target tissue according to an electric stimulation signal generated by a stimulation clock; sampling a response signal of the target tissue according to a sampling clock independent of the stimulation clock to obtain a sampling signal sequence; executing electric stimulation output in each phase synchronization period, sampling the response signal according to the sampling clock; when reaching the phase synchronization period, resetting a stimulation period count, and re-establishing a phase reference of the electric stimulation output according to the reset stimulation period count; generating a stimulation artifact sequence according to the sampling signal sequence in multiple phase synchronization periods; and removing the stimulation artifact in the sampling signal sequence according to the sampling signal sequence and the stimulation artifact sequence to obtain a target deep brain field potential signal. The application can remove the stimulation artifact without establishing a fixed multiple relationship between the stimulation clock and the sampling clock.

Description

Technical Field

[0001] This application relates to the field of deep brain field potential signal processing technology, and more specifically to a method and system for removing electrical stimulation artifacts based on periodic phase synchronization. Background Technology

[0002] Deep brain stimulation (DBS) is a neuromodulation technique that modulates neural activity by continuously delivering electrical impulses to specific brain regions. It is widely used in the treatment of neurological disorders such as Parkinson's disease, dystonia, epilepsy, and treatment-resistant mental illnesses. During DBS, implanted stimulating electrodes deliver stimulation pulses to the target brain region while simultaneously acquiring information about the neural activity state of that region through local field potential (LFP) signal acquisition.

[0003] However, during actual stimulation, the high-amplitude stimulation pulses output by the stimulation electrodes will generate obvious stimulation artifacts in the acquisition channel. These stimulation artifacts are usually characterized by high amplitude, long duration, and periodic repetition. Their amplitude is often much higher than the amplitude of the real deep brain field potential signal, which causes the acquired deep brain field potential signal to be submerged by the stimulation artifacts, affecting the accuracy of subsequent neural activity analysis and closed-loop regulation.

[0004] Existing technologies typically employ synchronous sampling or fixed-multiple sampling methods to remove stimulus artifacts. For example, by using a unified clock source to drive the stimulus clock and the acquisition clock, a fixed multiple relationship is maintained between the sampling time and the stimulus pulse output time. This allows for the creation of a stimulus artifact template based on a fixed stimulus phase position, and artifact removal is achieved using template subtraction. However, these synchronous methods usually require a strict clock synchronization between the stimulus module and the acquisition module. Therefore, the stimulus frequency and sampling frequency often need to satisfy a fixed multiple relationship or an integer period correspondence. When the stimulus frequency, sampling frequency, or system operating state changes, cumulative phase drift can easily occur between the stimulus output timing and the sampling timing, resulting in phase mismatch between the stimulus artifact template and the actual stimulus artifact, thereby reducing the accuracy of stimulus artifact removal. Summary of the Invention

[0005] This application provides a method and system for removing electrical stimulation artifacts based on periodic phase synchronization. Under the condition that the stimulation clock and the acquisition clock operate independently and asynchronously, a stable phase correspondence relationship of stimulation artifacts between different phase synchronization periods is achieved, and stimulation artifact removal is achieved without the need to establish a fixed multiple relationship.

[0006] In a first aspect, this application provides a method for removing electrical stimulation artifacts based on periodic phase synchronization, comprising: periodically stimulating a target tissue with an electrical stimulation signal generated according to a stimulation clock; sampling the response signal of the target tissue according to an acquisition clock independent of the stimulation clock to obtain a sampled signal sequence; performing electrical stimulation output in each phase synchronization cycle according to a set phase synchronization cycle, and performing response signal sampling according to the acquisition clock; when the phase synchronization cycle is reached, resetting the stimulation cycle count, and re-establishing the phase reference of the electrical stimulation output according to the reset stimulation cycle count, so that the stimulation artifacts in different phase synchronization cycles maintain periodic phase consistency; generating a stimulation artifact sequence based on the sampled signal sequences in multiple phase synchronization cycles; and removing the stimulation artifacts in the sampled signal sequence according to the sampled signal sequence and the stimulation artifact sequence to obtain a target deep brain field potential signal after stimulation artifact removal.

[0007] In one optional embodiment of the first aspect, the step of performing electrical stimulation output within each phase synchronization cycle according to a set phase synchronization cycle includes: establishing a periodic synchronization window corresponding to the duration of the pre-set phase synchronization cycle based on the acquired duration of the phase synchronization cycle; at the beginning of the periodic synchronization window, starting stimulation cycle counting according to a stimulation clock, and performing periodic electrical stimulation output according to a set stimulation frequency and stimulation pulse width; during the execution of periodic electrical stimulation output, continuously sampling the response signal of the target tissue according to a sampling clock to obtain a sampling signal sequence corresponding to the current periodic synchronization window; within the periodic synchronization window, accumulating and counting the number of stimulation pulse outputs, and determining the periodic position corresponding to the current stimulation output based on the accumulated counting result; triggering a periodic phase synchronization operation after reaching the end time of the periodic synchronization window, and limiting the cumulative phase drift of stimulation artifacts between different phase synchronization cycles by recalibrating the stimulation output phase, so as to keep the periodic phase of stimulation artifacts consistent within different phase synchronization cycles.

[0008] In one optional embodiment of the first aspect, the step of resetting the stimulation cycle count when the phase synchronization period is reached, and re-establishing the phase reference of the electrical stimulation output based on the reset stimulation cycle count, includes: stopping the current stimulation pulse output and maintaining the acquisition state of the current sampled signal sequence after detecting that the current stimulation output has reached the end time of the cycle corresponding to the phase synchronization period; clearing the stimulation cycle counter corresponding to the current stimulation output to eliminate the cumulative count deviation in the previous phase synchronization period; regenerating the stimulation output timing based on the cleared stimulation cycle count, and starting the electrical stimulation output corresponding to the next phase synchronization period based on the regenerated stimulation output timing; taking the time corresponding to the first stimulation pulse after restarting as the new stimulation phase reference point, and establishing the stimulation output phase corresponding to the next phase synchronization period based on the new stimulation phase reference point, so that the stimulation start phase between adjacent phase synchronization periods remains consistent, thereby limiting the cumulative phase drift of stimulation artifacts between consecutive phase synchronization periods and maintaining the periodic phase consistency of stimulation artifacts.

[0009] In one alternative embodiment of the first aspect, sampling the response signal of the target tissue according to an acquisition clock independent of the stimulation clock includes: controlling the output frequency and output pulse width of the electrical stimulation signal according to a stimulation clock generated by a first clock source; controlling the sampling frequency of the response signal according to an acquisition clock generated by a second clock source; establishing a corresponding stimulation output timing sequence according to the stimulation clock, and establishing a corresponding signal sampling timing sequence according to the acquisition clock; during the electrical stimulation output process, executing stimulation pulse output according to the stimulation output timing sequence, and executing response signal sampling according to the signal sampling timing sequence, so that the stimulation output timing sequence and the signal sampling timing sequence operate independently according to their respective clock cycles, thereby realizing asynchronous timing control between electrical stimulation output and response signal acquisition.

[0010] In one alternative embodiment of the first aspect, the asynchronous timing control between electrical stimulation output and response signal acquisition includes: acquiring response signal sampling data corresponding to different stimulation cycles during continuous stimulation output; establishing a sampling data relationship corresponding to different stimulation phase positions based on the stimulation pulse output position corresponding to each response signal sampling data; and acquiring response signal sampling data covering the entire stimulation cycle based on the corresponding relationship of stimulation phase positions in different stimulation cycles, so as to maintain the phase consistency of stimulation artifacts between different phase synchronization cycles.

[0011] In one optional embodiment of the first aspect, generating a stimulus artifact sequence based on sampled signal sequences within multiple phase synchronization periods includes: acquiring sampled signal sequences corresponding to multiple phase synchronization periods; aligning the phase positions of the sampled signal sequences within the multiple phase synchronization periods according to stimulus phase reference points corresponding to each phase synchronization period; arranging the phase-aligned sampled signal sequences in chronological order; performing a moving average processing on the arranged sampled signal sequences to retain recurring periodic stimulus response components within the multiple phase synchronization periods; and generating a corresponding stimulus artifact sequence based on the periodic stimulus response components.

[0012] In one alternative embodiment of the first aspect, the step of performing a moving average processing on the arranged sampled signal sequence includes: establishing a moving data window containing multiple phase synchronization period sampled data; determining the number of phase synchronization periods participating in the moving average calculation according to a preset window length; after acquiring new phase synchronization period sampled data, adding the latest phase synchronization period sampled data to the moving data window and removing the earliest phase synchronization period sampled data added to the moving data window; performing an average calculation on the sampled data corresponding to the same phase position within the moving data window to generate an updated stimulus artifact sequence; and tracking the changes in stimulus artifact waveforms according to the updated stimulus artifact sequence to improve the adaptability of the stimulus artifact removal process to changes in stimulus state.

[0013] In one optional embodiment of the first aspect, the step of removing stimulus artifacts from the sampled signal sequence based on the sampled signal sequence and the stimulus artifact sequence includes: acquiring a stimulus artifact sequence corresponding to the current sampled signal sequence; performing temporal matching on the stimulus artifact sequence based on the stimulus phase position corresponding to the current sampled signal sequence; calculating the corresponding point difference between the temporally matched stimulus artifact sequence and the sampled signal sequence to generate a corresponding difference signal sequence; eliminating periodic stimulus artifact components from the sampled signal sequence based on the difference signal sequence, while retaining non-periodic deep brain potential response components; and determining the difference signal sequence after stimulus artifact removal as the target deep brain potential signal.

[0014] In one alternative of the first aspect, the step of re-establishing the phase reference of the electrical stimulation output based on the reset stimulation cycle count includes: determining the first stimulation pulse output time after restarting within each phase synchronization cycle as a unified stimulation phase reference point; performing phase position correspondence on the stimulation output timing sequence in different phase synchronization cycles based on the unified stimulation phase reference point; and establishing a stimulation phase offset constraint relationship between different phase synchronization cycles based on the corresponding stimulation output timing sequence.

[0015] Secondly, this application provides a system for removing electrical stimulation artifacts based on periodic phase synchronization, using the method described in any one of the first aspects. The system includes: a stimulation output module for periodically stimulating a target tissue with an electrical stimulation signal generated according to a stimulation clock; a signal acquisition module for sampling the response signal of the target tissue according to an acquisition clock independent of the stimulation clock to obtain a sampled signal sequence; a periodic synchronization module for performing electrical stimulation output in each phase synchronization cycle according to a set phase synchronization cycle, and performing response signal sampling according to the acquisition clock; a phase reconstruction module for resetting the stimulation cycle count when the phase synchronization cycle is reached, and re-establishing a phase reference for the electrical stimulation output based on the reset stimulation cycle count, so that stimulation artifacts in different phase synchronization cycles maintain consistent periodic phase; an artifact generation module for generating a stimulation artifact sequence based on the sampled signal sequences in multiple phase synchronization cycles; and an artifact removal module for removing stimulation artifacts from the sampled signal sequence according to the sampled signal sequence and the stimulation artifact sequence, to obtain a target deep brain field potential signal after stimulation artifact removal.

[0016] It should be understood that the above general description and the following detailed description are merely exemplary and do not limit this application. Attached Figure Description

[0017] The accompanying drawings, which are incorporated herein and form part of this specification, illustrate one or more embodiments of the present application and, together with the description, serve to explain the principles of the present application and to enable those skilled in the art to make and use the present application.

[0018] Figure 1 This is a flowchart of an exemplary method for removing electrical stimulation artifacts based on periodic phase synchronization, according to some embodiments of this application.

[0019] Figure 2 is a schematic diagram of an independent clock drive for an exemplary stimulation output module and a signal acquisition module according to some embodiments of this application;

[0020] Figure 3 is a schematic diagram of an exemplary electrical stimulation output process according to some embodiments of this application;

[0021] Figure 4 is a schematic diagram of an exemplary synchronization waiting process between phase synchronization cycles according to some embodiments of this application;

[0022] Figure 5 is a flowchart of an exemplary periodic phase synchronization method according to some embodiments of this application;

[0023] Figure 6 is a schematic diagram of an exemplary process for stopping the output of a stimulation pulse according to some embodiments of this application;

[0024] Figure 7 is a flowchart of an exemplary asynchronous timing control method according to some embodiments of this application;

[0025] Figure 8 is a flowchart of an exemplary method for establishing the correspondence between stimulus phase positions according to some embodiments of this application;

[0026] Figure 9 is a flowchart of an exemplary stimulus artifact sequence generation method according to some embodiments of this application;

[0027] Figure 10 is a flowchart of an exemplary moving average processing method according to some embodiments of this application;

[0028] Figure 11 is a flowchart of an exemplary interpolation method for artifact removal according to some embodiments of this application;

[0029] Figure 12 is an exemplary diagram of difference calculation according to some embodiments of this application;

[0030] Figure 13 is a flowchart of an exemplary unified stimulus phase reference establishment method according to some embodiments of this application;

[0031] Figure 14 is a structural block diagram of an exemplary electrical stimulation artifact removal system based on periodic phase synchronization according to some embodiments of this application.

[0032] Figure labeling: Target brain region 20, Stimulation output module 201, Stimulation clock 2011, Stimulation clock generation unit 2012, Stimulation parameter control unit 2013, Stimulation pulse output unit 2014, Signal acquisition module 202, Acquisition clock 2021, Acquisition clock generation unit 2022, Analog front-end amplification unit 2023, Analog-to-digital conversion unit 2024, Sampling buffer unit 2025, Period synchronization module 203, Period synchronization timing unit 2031, Stimulation period counting unit 2032, Period synchronization triggering unit 2033, Phase reconstruction module 204, Count clearing unit 2041, Timing reconstruction unit 2042, Phase reference establishment unit 2043, Artifact generation module 205, Phase alignment unit 2051, Data arrangement unit 2052, Moving average unit 2053, Artifact removal module 206, Timing matching unit 2061, Difference calculation unit 2062, and Signal output unit 2063. Detailed Implementation

[0033] Exemplary embodiments will now be described more fully with reference to the accompanying drawings. However, these exemplary embodiments may be implemented in various forms and should not be construed as limited to the examples set forth herein; rather, the description of these embodiments is intended to make this application more comprehensive and complete, and to fully convey the concept of the exemplary embodiments to those skilled in the art. The described features, structures, or characteristics may be combined in any suitable manner in one or more embodiments. Numerous specific details are provided in the following description to provide a deeper understanding of embodiments of this application.

[0034] Figure 1 is an example of an electrical stimulation artifact removal method based on periodic phase synchronization provided in this application. The electrical stimulation artifact removal method includes steps S101-S106:

[0035] S101: Periodically electrically stimulate the target tissue according to the electrical stimulation signal generated by the stimulation clock; S102: Sample the response signal of the target tissue according to the acquisition clock, which is independent of the stimulation clock, to obtain a sampled signal sequence; S103: Perform electrical stimulation output in each phase synchronization cycle according to the set phase synchronization cycle, and perform response signal sampling according to the acquisition clock; S104: When the phase synchronization cycle is reached, reset the stimulation cycle count, and re-establish the phase reference of the electrical stimulation output according to the reset stimulation cycle count, so that the stimulation artifacts in different phase synchronization cycles maintain periodic phase consistency; S105: Generate a stimulation artifact sequence based on the sampled signal sequences in multiple phase synchronization cycles; S106: Remove the stimulation artifacts in the sampled signal sequence according to the sampled signal sequence and the stimulation artifact sequence to obtain the target deep brain field potential signal after stimulation artifact removal.

[0036] Specifically, the electrical stimulation artifact removal method is applied to the acquisition and artifact removal of local field potential (LFP) signals during deep brain stimulation (DBS). This method can extract and remove periodic stimulation artifacts generated during stimulation under the condition that the stimulation clock and the acquisition clock are independent of each other, so as to obtain the target local field potential signal after the stimulation artifacts are removed.

[0037] In this embodiment, as Figure 2As shown, the stimulation output module 201 and the signal acquisition module 202 are driven by independent clock sources. Specifically, the stimulation output module 201 uses a stimulation clock 2011 to generate an electrical stimulation signal, while the signal acquisition module 202 uses an acquisition clock 2021, which is independent of the stimulation clock 2011, to sample the response signal. The stimulation clock 2011 and the acquisition clock 2021 are generated by different oscillators, and there is no fixed multiple relationship between them, allowing the stimulation output and signal acquisition to operate independently according to their respective clock cycles.

[0038] In practice, the stimulation output module 201 generates periodic electrical stimulation signals according to preset stimulation parameters and outputs electrical stimulation pulses to the target brain region 20 through implanted stimulation electrodes. The stimulation parameters may include stimulation frequency, stimulation pulse width, and stimulation amplitude.

[0039] In this embodiment, the stimulation frequency is denoted as . The stimulation period is denoted as The stimulation period satisfies the following relationship:

[0040]

[0041] Stimulation frequency Setting it to 130Hz will change the stimulation cycle. It is approximately 7.69 ms, meaning the time interval between adjacent stimulus pulses is approximately 7.69 ms.

[0042] Furthermore, the sampling frequency is denoted as The sampling period is denoted as The sampling period satisfies the following relationship:

[0043]

[0044] Sampling frequency Setting it to 250Hz will increase the sampling period. Since the stimulation period and the sampling period are not integer multiples of each other, there is no fixed correspondence between the stimulation pulse output time and the response signal sampling time.

[0045] For example, during continuous operation, the first sampling point might be located 1 ms after the start of the stimulus pulse, the second sampling point might be located 5 ms after the start of the stimulus pulse, and the third sampling point might be located 1.31 ms after the start of the next stimulus cycle. Therefore, under asynchronous operation, the position of the sampling point relative to the stimulus pulse will continuously change over time, gradually covering the different stimulus phase positions in the complete stimulus cycle.

[0046] This embodiment further introduces a periodic phase synchronization mechanism to limit the cumulative phase drift of stimulus artifacts during long-term operation.

[0047] In practice, a phase synchronization period is preset, and the phase synchronization period is denoted as... In this embodiment Set to 1 second. Within each phase synchronization cycle, the stimulation output module 201 continuously outputs stimulation pulses according to the stimulation clock 2011, while the signal acquisition module 202 continuously performs response signal sampling according to the acquisition clock 2021.

[0048] The number of stimulation pulses within one phase synchronization cycle is denoted as , The following relationship must be satisfied:

[0049]

[0050] when =130Hz, When =1s, we can obtain =130, meaning that a total of 130 stimulation pulses are output within one phase synchronization cycle.

[0051] Furthermore, the number of sampling points within one phase synchronization period is denoted as... , The following relationship must be satisfied:

[0052]

[0053] when =250Hz, When =1s, we can obtain =250, meaning a total of 250 sampling points are obtained within one phase synchronization cycle. After the current phase synchronization cycle ends, a periodic phase synchronization operation is triggered.

[0054] Furthermore, the frequency errors of the stimulation clock 2011 and the acquisition clock 2021 are both controlled within ±10ppm. Therefore, the maximum cumulative time error generated during system operation is denoted as... , The following relationship must be satisfied:

[0055]

[0056] Among them, 20 This indicates the maximum combined frequency error between the stimulation clock 2011 and the acquisition clock 2021.

[0057] when When =1s, we can obtain =20μs. Since 20μs is much smaller than the stimulation period of 7.69ms, stimulation artifacts between different phase synchronization periods can maintain a high degree of phase consistency.

[0058] Furthermore, a stimulus artifact sequence is generated based on the sampled signal sequence within multiple phase synchronization cycles.

[0059] In practice, the sampling signals in multiple phase synchronization cycles are first aligned according to the stimulus phase reference point, and then the sampling data corresponding to the same stimulus phase position are processed by moving average.

[0060] Stimulus artifact sequence denoted as The sampled data corresponding to the i-th phase synchronization cycle is denoted as Let N be the number of phase synchronization cycles involved in the moving average calculation. Then, the stimulus artifact sequence satisfies the following relationship:

[0061]

[0062] For example, when averaging 20 consecutive phase synchronization cycles, random noise can theoretically be reduced to 22.4% of the original value, preserving the periodic stimulus artifacts while weakening the random deep brain field potentials and random noise.

[0063] Secondly, the system removes stimulus artifacts from the sampled signal based on the stimulus artifact sequence. The original sampled signal is denoted as... The target brain deep field potential signal after artifact removal is denoted as The artifact removal process then satisfies the following relationship:

[0064]

[0065] For example, when the peak-to-peak value of the original sampled signal is 3mV, the amplitude of the stimulus artifact is about 2.7mV, and the amplitude of the real deep brain field potential signal is about 0.3mV, after the above-mentioned stimulus artifact removal process, the residual amplitude of the stimulus artifact can be reduced to below 50μV, which can improve the recognition effect of deep brain field potential signals.

[0066] In this embodiment, a periodic phase synchronization mechanism is used to achieve phase alignment and template extraction of stimulus artifacts under the condition that the stimulation clock and the acquisition clock are independent of each other. Stimulation artifact removal can be completed without establishing a fixed synchronization relationship between the stimulation clock and the acquisition clock. This embodiment makes the system architecture more flexible and more suitable for asynchronous signal processing scenarios in implantable brain-computer interface systems and closed-loop deep brain stimulation systems.

[0067] Figure 3This is an example of the electrical stimulation output process within each phase synchronization cycle provided in the embodiments of this application, wherein the electrical stimulation output process includes the following steps S111-S114:

[0068] S111: Establish a periodic synchronization window corresponding to the pre-set phase synchronization period duration based on the acquired phase synchronization period duration; S112: At the beginning of the periodic synchronization window, start the stimulation cycle counting according to the stimulation clock, and perform periodic electrical stimulation output according to the set stimulation frequency and stimulation pulse width. During the execution of periodic electrical stimulation output, continuously sample the response signal of the target tissue according to the acquisition clock to obtain the sampling signal sequence corresponding to the current periodic synchronization window; S113: Within the periodic synchronization window, accumulate and count the number of stimulation pulse outputs, and determine the periodic position corresponding to the current stimulation output based on the accumulated count result; S114: After reaching the end time of the periodic synchronization window, trigger the periodic phase synchronization operation, and limit the cumulative phase drift of stimulation artifacts between different phase synchronization cycles by recalibrating the stimulation output phase, so that the stimulation artifacts in different phase synchronization cycles maintain consistent periodic phase.

[0069] This embodiment, based on the above embodiment, further explains the synchronization waiting process after the phase synchronization period ends.

[0070] As shown in Figure 4, within each phase synchronization cycle, the system continuously performs periodic electrical stimulation output and continuously samples the target tissue response signal according to the acquisition clock. Specifically, within the current phase synchronization cycle, the system counts the number of stimulation pulses output in the current cycle based on the stimulation cycle count. When the cumulative number of stimulation pulses reaches the preset number of stimulations, the system stops the current stimulation output and enters a synchronization waiting phase.

[0071] During the synchronization waiting phase, the system continues to run the response signal sampling process while pausing the output of new stimulation pulses to wait for the next phase synchronization moment. When the next phase synchronization moment is detected, the system restarts the stimulation output and determines the first stimulation pulse output moment after the restart as the new stimulation phase reference point, and enters the next phase synchronization cycle.

[0072] In this embodiment, there is a synchronization waiting phase between adjacent phase synchronization cycles, so that the stimulus output in different phase synchronization cycles can re-establish a unified stimulus phase reference relationship.

[0073] This embodiment, by setting a synchronization waiting phase between phase synchronization cycles, allows the system to re-establish the phase reference relationship corresponding to the stimulus output before entering the next phase synchronization cycle. This reduces phase shifts generated during long-term continuous operation and facilitates subsequent processing of stimulus artifacts in different phase synchronization cycles. Figure 3 As shown in the figure, this embodiment further explains the process of performing electrical stimulation output in each phase synchronization cycle according to the set phase synchronization cycle.

[0074] In this embodiment, the system first acquires a pre-set phase synchronization period duration and establishes a corresponding periodic synchronization window based on the phase synchronization period duration. The phase synchronization period duration can be set according to the stimulation frequency, sampling frequency, clock precision, and allowable phase drift range.

[0075] In practical implementation, the phase synchronization period can be denoted as: , The time can be set to 0.5 seconds, 1 second, 2 seconds, or other preset time lengths. In this embodiment, 1 second is used as an example for explanation, that is, the system performs a periodic phase synchronization operation once every 1 second.

[0076] After establishing the periodic synchronization window, at the beginning of each periodic synchronization window, the system starts the stimulation cycle counting according to the stimulation clock and performs periodic electrical stimulation output according to the set stimulation frequency and stimulation pulse width. In this embodiment, the stimulation frequency... Stimulation cycle Sampling frequency and sampling period The calculation method is the same as in the above embodiments, and will not be repeated here.

[0077] Furthermore, within the current period synchronization window, the system continuously outputs stimulation pulses and continuously samples the response signal of the target tissue according to the acquisition clock to form a sampling signal sequence corresponding to the current period synchronization window. Since the stimulation clock and the acquisition clock operate asynchronously, there is no integer multiple relationship between the stimulation period and the sampling period. Therefore, the relative position between the response signal sampling time and the stimulation pulse output time continuously changes over time. For example, during continuous operation, different sampling points will be located at different time positions after the stimulation pulse, gradually covering different stimulation phase regions in the complete stimulation period. Therefore, within a single period synchronization window, the system can acquire response signal sampling data corresponding to multiple stimulation phase positions.

[0078] Furthermore, within the current periodic synchronization window, the system accumulates and counts the number of stimulus pulse outputs, and determines the periodic position corresponding to the current stimulus output based on the accumulated count results. By recording the stimulus phase positions corresponding to different stimulus pulses, the correspondence between the stimulus output phase and the sampled signal within the current periodic synchronization window can be established.

[0079] In this embodiment, the number of stimulation pulses within a periodic synchronization window and number of sampling points The calculation method is the same as in the above embodiment. When the stimulation frequency is 130Hz and the phase synchronization period is 1s, a total of 130 stimulation pulses are output within one period synchronization window. When the sampling frequency is 250Hz, a total of 250 sampling points are obtained within one period synchronization window.

[0080] Furthermore, within the periodic synchronization window, the system cumulatively counts the number of stimulation pulse outputs and determines the periodic position phase of the current stimulation pulse within the phase synchronization period based on the cumulative count result. For example, when the stimulation period count value is n, the corresponding periodic position phase satisfies the following relationship:

[0081]

[0082] in, This indicates the periodic position and phase of the nth stimulus pulse within the current phase synchronization period. This indicates the total number of stimulation pulses within the current phase synchronization period. Within a period synchronization window, different stimulation pulses can correspond to different period phase positions.

[0083] After the end of the periodic synchronization window is reached, the system triggers a periodic phase synchronization operation to limit the cumulative phase drift between the stimulus output timing and the sampling timing. In practice, the system re-establishes a unified periodic start position for the stimulus output in the next periodic synchronization window based on the end position of the current periodic synchronization window.

[0084] For example, under conditions where the stimulation clock and the acquisition clock operate asynchronously, frequency errors and clock drift exist between them. The relative position between the stimulation pulse output time and the sampling time will continuously accumulate and change. If periodic phase synchronization is not performed, the relative relationship between the stimulation pulse output position and the sampling position will continue to drift, causing stimulation artifacts between different cycles to gradually lose phase consistency. However, this embodiment, by re-establishing a unified stimulation phase reference after the end of each periodic synchronization window, allows stimulation pulses in different phase synchronization cycles to restart counting from a unified phase position, limiting the long-term cumulative phase drift of stimulation artifacts.

[0085] Furthermore, by limiting the cumulative phase drift to a preset range, the stimulus artifacts formed in different phase synchronization cycles can maintain a consistent phase distribution structure, ensuring that stimulus artifacts in multiple phase synchronization cycles can be aligned.

[0086] In this embodiment, the duration of the periodic synchronization window can be adjusted according to the maximum phase drift allowed by the system. For example, when the accuracy of the stimulation clock and the acquisition clock is high, the duration of the periodic synchronization window can be extended; while when the clock drift is large, the duration of the periodic synchronization window can be shortened to further reduce the cumulative phase offset between different phase synchronization cycles.

[0087] By setting a periodic synchronization window, the system can achieve periodic phase constraint of stimulus artifacts even when the stimulus clock and the acquisition clock are not multiples of each other.

[0088] This embodiment further explains the process of resetting the stimulation cycle count when the phase synchronization period is reached, and re-establishing the electrical stimulation output phase reference based on the reset stimulation cycle count.

[0089] When the stimulation cycle count reaches the end position corresponding to the current phase synchronization cycle, the system triggers a periodic phase synchronization operation, as shown in Figure 5. The periodic phase synchronization operation includes the following steps S121-S124:

[0090] S121: Stop the current stimulus pulse output; S122: Reset the current stimulus cycle count to zero; S123: Re-establish a new stimulus output timing sequence based on the reset stimulus cycle count; S124: Restart the stimulus pulse output corresponding to the next phase synchronization cycle. The first stimulus pulse output time after restarting is used as the phase reference start point for the next phase synchronization cycle.

[0091] In practice, the system monitors the cycle count status corresponding to the current stimulus output in real time, and determines whether the current stimulus output has reached the end of the cycle based on the preset phase synchronization cycle.

[0092] When the current stimulus output is detected to have reached the end of the phase synchronization period, the system first stops the current stimulus pulse output to avoid generating new stimulus pulses during the phase reconstruction process, as shown in Figure 6. The process of stopping the stimulus pulse output may include the following steps S1211-S1213:

[0093] S1211: Turn off the current stimulus pulse generation control signal; S1212: Stop the current stimulus output timing link; S1213: Latch the current stimulus cycle counting state.

[0094] Meanwhile, the signal acquisition module maintains the current response signal sampling state unchanged, that is, it continues to sample the response signal during the stimulus pause to ensure the acquisition of a continuous sampling signal sequence.

[0095] Furthermore, the system performs a zeroing process on the stimulation cycle counter corresponding to the current stimulus output to eliminate the cumulative count deviation in the previous phase synchronization cycle.

[0096] In practice, the stimulation period counter is used to record the number of stimulation pulses output within the current phase synchronization period. For example, when the stimulation period count reaches the total number of stimulation pulses corresponding to the current phase synchronization period, the system resets the stimulation period count to zero, i.e., ... =0.

[0097] Furthermore, after the counter is cleared, the system regenerates the stimulation output timing based on the cleared stimulation cycle count, and starts the electrical stimulation output corresponding to the next phase synchronization cycle based on the regenerated stimulation output timing.

[0098] In practice, the system resets the zeroed count starting point as the initial stimulus output position and re-establishes the subsequent stimulus pulse output sequence according to the stimulus cycle. For example, the first stimulus pulse output time after restarting is recorded as... Then, the output time of the subsequent nth stimulus pulse satisfies the following relationship:

[0099]

[0100] in, This indicates the time when the nth stimulus pulse is output. This indicates the stimulation cycle.

[0101] Furthermore, the system uses the moment corresponding to the first stimulus pulse after restarting as the new stimulus phase reference point, and establishes the stimulus output phase corresponding to the next phase synchronization cycle based on the new stimulus phase reference point. For example, when the first stimulus pulse after restarting is output, the system defines the current stimulus phase as... =0, and subsequent stimulation pulses are periodically incremented based on this stimulation phase reference point, and the stimulation initiation phase can be kept consistent between adjacent phase synchronization periods.

[0102] Furthermore, since the stimulation clock and the acquisition clock are generated by independent oscillators, a cumulative phase shift will gradually occur between the stimulation output timing and the sampling timing during long-term continuous operation of the system. For example, when the system runs continuously without performing periodic phase synchronization, the stimulation pulse output position in different phase synchronization cycles will gradually deviate from the original stimulation phase reference position, causing phase drift of stimulation artifacts between different cycles. However, this embodiment, by re-establishing a unified stimulation phase reference point after each phase synchronization cycle, can re-constrain the stimulation output phase to the unified periodic reference position, and the stimulation artifacts in different phase synchronization cycles can maintain a stable and consistent phase distribution structure.

[0103] Furthermore, during the subsequent generation of stimulus artifacts, the system can perform phase alignment of stimulus artifacts in multiple phase synchronization cycles based on a unified stimulus phase reference, thereby improving the accuracy of stimulus artifacts.

[0104] In this embodiment, the stimulation cycle counter can be cleared by hardware or by software. The process of re-establishing the stimulation output timing sequence can be completed by digital control logic or by the microprocessor reconfiguring the output timing parameters according to the preset stimulation parameters. This embodiment does not limit this.

[0105] Through the above method, this embodiment achieves phase constraint of stimulus artifacts under the condition that the stimulation clock and the acquisition clock operate independently of each other, thereby improving the effect of stimulus artifact removal in asynchronous neuromodulation systems.

[0106] This embodiment, based on the above embodiment, further explains the process of sampling the response signal of the target tissue according to an acquisition clock independent of the stimulation clock, as shown in Figure 7. The asynchronous timing control method includes the following steps S131-S133:

[0107] S131: Control the output frequency and output pulse width of the electrical stimulation signal according to the stimulation clock generated by the first clock source; S132: Control the sampling frequency of the response signal according to the acquisition clock generated by the second clock source; S133: Establish the corresponding stimulation output timing sequence according to the stimulation clock and the corresponding signal sampling timing sequence according to the acquisition clock. During the electrical stimulation output process, the stimulation pulse is output according to the stimulation output timing sequence and the response signal is sampled according to the signal sampling timing sequence, so that the stimulation output timing sequence and the signal sampling timing sequence run independently according to their respective clock cycles, so as to realize asynchronous timing control between electrical stimulation output and response signal acquisition.

[0108] In this embodiment, the system uses an asynchronous dual-clock structure to control the electrical stimulation output and the response signal sampling respectively.

[0109] In specific implementation, the system includes a first clock source and a second clock source. The first clock source and the second clock source are each constructed using independent oscillators. The first clock source is used to generate the stimulation clock, and the second clock source is used to generate the acquisition clock.

[0110] In practical implementation, the first clock source can be a first crystal oscillator digital clock generator used to generate the corresponding stimulus clock signal, and the second clock source can be a second crystal oscillator or digital clock generator set independently of the first clock source used to generate the corresponding acquisition clock signal. For example, the stimulus output module uses a 32MHz crystal oscillator to generate the stimulus clock, and the signal acquisition module uses a 24MHz crystal oscillator to generate the acquisition clock. The first and second clock sources each have independent timing references, and there is no need to establish a unified master-slave clock relationship or a fixed multiple relationship between them.

[0111] After generating the stimulation clock and the acquisition clock, the system generates the stimulation output timing sequence and the sampling timing sequence through independent links. For example, the stimulation output module can generate a 130Hz stimulation output timing sequence through the first link, and the signal acquisition module can generate a 250Hz sampling timing sequence through the second link. The stimulation output timing sequence is only controlled by the stimulation clock, and the sampling timing sequence is only controlled by the acquisition clock, so that an asynchronous timing relationship is formed between the stimulation pulse output and the response signal sampling.

[0112] Furthermore, the system controls the output frequency and output pulse width of the electrical stimulation signal based on the stimulation clock generated by the first clock source.

[0113] In practice, the stimulation output module establishes a corresponding stimulation output timing sequence based on the stimulation clock, and controls the output time, output period, and output pulse width of the stimulation pulse according to the stimulation output timing sequence. For example, under the condition of stimulation frequency of 130Hz, the stimulation output module executes a stimulation pulse output once after one stimulation cycle.

[0114] Furthermore, the system controls the sampling frequency of the response signal based on the acquisition clock generated by the second clock source.

[0115] In practice, the signal acquisition module establishes the corresponding signal sampling timing sequence based on the acquisition clock, and performs continuous sampling of the target organization's response signal according to the signal sampling timing sequence. For example, under the condition of a sampling frequency of 250Hz, the signal acquisition module performs analog-to-digital conversion sampling once every sampling cycle.

[0116] Furthermore, the stimulus output timing and the signal sampling timing operate independently according to their respective clock cycles.

[0117] In practice, during the electrical stimulation output process, the stimulation output module drives the stimulation pulse output according to the stimulation clock, and the signal acquisition module drives the analog-to-digital conversion sampling according to the acquisition clock.

[0118] Since the stimulus output module and the signal acquisition module are established using different clock sources, they can operate independently according to their respective clock cycles. The stimulus output process will not adjust the sampling time, and the sampling process will not follow the stimulus pulse output time. The system can achieve asynchronous timing control between stimulus output and response signal sampling without establishing a unified multiple clock structure.

[0119] Under this asynchronous timing control, the stimulation frequency and the sampling frequency do not need to satisfy a fixed integer multiple relationship. Therefore, the system does not need to reconfigure a unified synchronization clock for different stimulation parameters. For example, in a traditional synchronous sampling system, when the stimulation frequency changes, it is usually necessary to adjust the sampling frequency synchronously or re-establish the synchronous sampling relationship. However, in this embodiment, the stimulation output module and the signal acquisition module can operate according to independent clocks. Therefore, even if the stimulation frequency changes, the sampling module can still maintain the original sampling timing.

[0120] Meanwhile, the sampling location of the response signal can cover different stimulation phase regions within the complete stimulation cycle. For example, in the initial stage, the sampling point may be located about 1 ms after the start of the stimulation pulse. After several stimulation cycles, the sampling point may move to about 3 ms after the start of the stimulation pulse. Continuing to run, the sampling point may move to about 6 ms after the start of the stimulation pulse. During continuous operation, the system can gradually acquire response signal sampling data corresponding to different stimulation phase positions within the complete stimulation cycle.

[0121] Furthermore, the system reduces the clock coupling between the stimulus output module and the signal acquisition module through an asynchronous dual-clock structure. Changes in the stimulus frequency will not forcibly alter the sampling frequency, and adjustments to the sampling frequency will not affect the stimulus output rhythm. For example, when the stimulus frequency is adjusted from 130Hz to 180Hz, the system can still maintain a sampling frequency of 250Hz; or, when the sampling frequency is increased from 250Hz to 500Hz, the stimulus output frequency can still maintain the original stimulus parameters.

[0122] In this embodiment, the clock accuracy of the first clock source and the second clock source can be controlled within ±10ppm respectively, so as to limit the long-term cumulative drift between the stimulus output timing and the sampling timing during continuous operation.

[0123] In this embodiment, under the condition that the stimulation clock and the acquisition clock are independent of each other, asynchronous timing control between electrical stimulation output and response signal acquisition is realized, enabling the system to acquire response signal sampling data corresponding to different stimulation phase positions, so as to synchronize the phase of the subsequent execution cycle and generate stimulation artifacts.

[0124] This embodiment further explains the asynchronous timing control between electrical stimulation output and response signal acquisition based on the above embodiment. As shown in Figure 8, the method for establishing the correspondence between stimulation phase positions includes the following steps S141-S143:

[0125] S141: During continuous stimulus output, acquire response signal sampling data corresponding to different stimulus cycles; S142: Based on the stimulus pulse output position corresponding to each response signal sampling data, establish the sampling data relationship corresponding to different stimulus phase positions; S143: Based on the corresponding relationship of stimulus phase positions in different stimulus cycles, acquire response signal sampling data covering the entire stimulus cycle, so as to maintain the phase consistency of stimulus artifacts between different phase synchronization cycles.

[0126] In this embodiment, the system determines the output time of the stimulus pulse based on the stimulus output timing sequence and determines the sampling time of the response signal based on the signal sampling timing sequence. The stimulus output timing sequence is generated by the stimulus clock, and the signal sampling timing sequence is generated by the acquisition clock.

[0127] In practice, the timing of the stimulus pulse output satisfies the following relationship:

[0128]

[0129] in, This indicates the time when the nth stimulus pulse is output. Indicates the initial stimulus output time. This indicates the stimulation cycle.

[0130] Accordingly, the sampling time of the response signal satisfies the following relationship:

[0131]

[0132] in, This represents the m-th sampling time. Indicates the initial sampling time. Indicates the sampling period.

[0133] Furthermore, in this embodiment, since there is no integer multiple relationship between the stimulation period and the sampling period, the position of the response signal sampling time relative to the stimulation pulse output time will continuously change over time.

[0134] In practice, the system does not implement fixed synchronization control for the sampling positions, but instead allows phase shifts in the sampling positions between consecutive stimulation cycles. For example, when the stimulation frequency is 130Hz and the sampling frequency is 250Hz, the time interval between adjacent stimulation pulses is approximately 7.69ms, and the time interval between adjacent sampling points is approximately 4ms. The first sampling point may be located approximately 0ms after the current stimulation pulse, the second sampling point may be located approximately 4ms after the current stimulation pulse, and the third sampling point may be located approximately 0.31ms after the next stimulation pulse. Subsequent sampling points continue to move between different stimulation cycles.

[0135] Furthermore, the system determines the sampling phase within the stimulation period corresponding to the current sampling point based on the time difference between the sampling time and the stimulation pulse output time. The time difference between the sampling time and the current stimulation pulse output time is denoted as... The sampling phases within the corresponding stimulus period satisfy the following relationship:

[0136]

[0137] in, This indicates the sampling phase within the stimulation period corresponding to the current sampling point. This represents the stimulation period. At different sampling times, the system can acquire response signal sampling data corresponding to the sampling phase position within different stimulation periods.

[0138] Furthermore, the system constructs a stimulus phase coverage set based on the response signal sampling data corresponding to the sampling phase within different stimulus cycles.

[0139] In practice, the system arranges the sampled data according to the sampling phase magnitude within the stimulation cycle and statistically analyzes the distribution of sampling points within the sampling phase intervals of different stimulation cycles. For example, the system can divide a complete stimulation cycle into multiple sampling phase intervals within stimulation cycles, including... , , wait.

[0140] The system then analyzes the distribution of sampled data in the sampling phase intervals within each stimulation cycle. When corresponding sampled data exists in the sampling phase intervals within each stimulation cycle, it indicates that the current sampling process has formed a complete stimulation phase coverage. Therefore, during continuous operation, the system can acquire response signal sampling data corresponding to different stimulation phase positions, so that the response signal sampling completely covers different stimulation phase regions in the stimulation cycle.

[0141] This embodiment, based on the above embodiment, further explains the process of generating a stimulus artifact sequence from a sampled signal sequence within multiple phase synchronization periods, such as... Figure 9As shown, the method for generating stimulus artifact sequences includes the following steps S151-S155:

[0142] S151: Obtain the sampling signal sequences corresponding to multiple phase synchronization cycles; S152: Align the phase positions of the sampling signal sequences in multiple phase synchronization cycles according to the stimulus phase reference points corresponding to each phase synchronization cycle; S153: Arrange the sampled signal sequences after phase alignment in chronological order; S154: Perform a moving average processing on the arranged sampled signal sequences to retain the periodic stimulus response components that recur in multiple phase synchronization cycles; S155: Generate the corresponding stimulus artifact sequence based on the periodic stimulus response components.

[0143] In this embodiment, the system first acquires the sampling signal sequence corresponding to multiple phase synchronization cycles.

[0144] In practice, the system continuously samples the target tissue response signal according to the acquisition clock within each phase synchronization cycle, and generates a sampling signal sequence corresponding to the current phase synchronization cycle. For example, when the phase synchronization cycle is 1 second and the sampling frequency is 250 Hz, 250 sampling points can be obtained within each phase synchronization cycle.

[0145] The sequence of sampled signals corresponding to multiple consecutive phase synchronization cycles can be represented as follows: ,in, Let represent the sampled signal sequence corresponding to the Nth phase synchronization cycle, k represent the sampling point position in the current phase synchronization cycle, and N represent the number of phase synchronization cycles involved in generating the stimulus artifact sequence.

[0146] Furthermore, the system aligns the phase positions of the sampled signal sequences in multiple phase synchronization cycles based on the stimulus phase reference points corresponding to each phase synchronization cycle.

[0147] In practice, the system uses the start time of the stimulus output in each phase synchronization cycle as a unified stimulus phase reference point, and arranges the sampled data in different phase synchronization cycles according to the unified stimulus phase reference point. For example, when the first stimulus pulse in different phase synchronization cycles is used as the unified stimulus phase reference point, the system arranges the sampled data corresponding to the same stimulus phase position in different phase synchronization cycles to the same position. Therefore, the periodic stimulus response components in different phase synchronization cycles can form a correspondence at the same stimulus phase position.

[0148] Furthermore, the system arranges the sampled signal sequence after phase alignment in chronological order.

[0149] In practice, the system arranges the sampled data from different phase synchronization cycles sequentially according to the time position of the sampling points within the stimulation cycle, forming data sets corresponding to different stimulation phase positions. For example, the system can arrange sampled data located near the same stimulation phase position from multiple phase synchronization cycles as follows: This is to form a data sequence corresponding to the current stimulus phase position.

[0150] Furthermore, the system performs a moving average process on the sorted sampled signal sequence to retain the periodic stimulus response components that recur in multiple phase synchronization cycles.

[0151] In practice, the system performs an average value calculation on the data sequences corresponding to the same stimulus phase position. The average value calculation method can adopt the moving average calculation formula in the above embodiment. This will not be repeated here.

[0152] Stimulus artifacts are periodically recurring response components, thus exhibiting stable correspondences across multiple phase synchronization cycles. In contrast, non-periodic response components in deep brain field potential signals do not possess a fixed repetitive structure across different phase synchronization cycles. Therefore, after performing a moving average process, periodic stimulus response components are preserved, while non-periodic deep brain field potential response components are weakened.

[0153] This embodiment further illustrates the update process of performing moving average processing on the arranged sampled signal sequence based on the above embodiment, as shown in Figure 10. The moving average processing includes the following steps S161-S165:

[0154] S161: Establish a sliding data window containing multiple phase synchronization period sampling data; S162: Determine the number of phase synchronization periods participating in the moving average calculation according to the preset window length; S163: After acquiring new phase synchronization period sampling data, add the latest phase synchronization period sampling data to the sliding data window and remove the earliest phase synchronization period sampling data added to the sliding data window; S164: Perform average calculation on the sampling data corresponding to the same phase position within the sliding data window to generate an updated stimulus artifact sequence; S165: Track the changes in stimulus artifact waveforms according to the updated stimulus artifact sequence to improve the adaptability of the stimulus artifact removal process to changes in stimulus state.

[0155] In this embodiment, the system first establishes a sliding data window containing multiple phase synchronization period sampling data.

[0156] In practice, the system stores the sampled signal sequences corresponding to multiple consecutive phase synchronization cycles in a sliding data window, and determines the number of phase synchronization cycles participating in the moving average calculation based on a preset window length. For example, the system can set the preset window length to 10, 20, or 50 phase synchronization cycles. A larger window length can improve the stability of the stimulus artifact sequence; a smaller window length can improve the system's response speed to changes in stimulus state. For example, when the preset window length corresponds to 16 phase synchronization cycles, the sliding data window stores the sampled data corresponding to the most recent 16 phase synchronization cycles.

[0157] Furthermore, after acquiring new phase synchronization period sampling data, the system performs an update operation on the sliding data window.

[0158] In practice, the system adds the most recently acquired phase synchronization cycle sampling data to the sliding data window while removing the earliest phase synchronization cycle sampling data added to the sliding data window. For example, when the system acquires the sampling data corresponding to the 17th phase synchronization cycle, it adds the 17th phase synchronization cycle sampling data to the sliding data window and removes the 1st phase synchronization cycle sampling data. The sliding data window continues to store the sampling data corresponding to the most recent 16 phase synchronization cycles, thus continuously updating the sampling data in the sliding data window over time.

[0159] Furthermore, in this embodiment, the system performs average calculation on the sampled data corresponding to the same phase position within the sliding data window to generate an updated stimulus artifact sequence. The updated stimulus artifact sequence can synchronously reflect the stimulus response changes under the current stimulus state, and the system can track the changes in the stimulus artifact waveform based on the updated stimulus artifact sequence. For example, when the impedance of the stimulating electrode changes, the stimulus amplitude changes, or the state of the target tissue interface changes, the stimulus artifact waveform may change accordingly. The average calculation method can adopt the moving average calculation method in the above embodiment, which will not be repeated here.

[0160] Furthermore, the system uses an updatable sliding data window to prevent fixed historical data from affecting the current stimulus artifact sequence generation result. For example, if the stimulus state changes, but the stimulus artifact sequence still relies on early historical sampling data, it may lead to a deviation between the current stimulus artifact structure and the historical stimulus artifact structure. In this embodiment, because the system continuously removes early phase synchronization period sampling data and adds the latest phase synchronization period sampling data, the stimulus artifact sequence can adapt to changes in the current stimulus state, and the system can improve the adaptability of the stimulus artifact removal process to changes in the stimulus state.

[0161] This embodiment, based on the above embodiment, further explains the process of removing stimulus artifacts from the sampled signal according to the sampled signal sequence and the stimulus artifact sequence. As shown in Figure 11, the difference method for artifact removal includes the following steps S171-S175:

[0162] S171: Obtain the stimulus artifact sequence corresponding to the current sampled signal sequence; S172: Perform temporal matching on the stimulus artifact sequence according to the stimulus phase position corresponding to the current sampled signal sequence; S173: Calculate the corresponding point difference between the temporally matched stimulus artifact sequence and the sampled signal sequence to generate a corresponding difference signal sequence; S174: Eliminate the periodic stimulus artifact component in the sampled signal sequence according to the difference signal sequence, and retain the non-periodic deep brain field potential response component; S175: Determine the difference signal sequence after stimulus artifact elimination as the target deep brain field potential signal.

[0163] In this embodiment, the system first obtains the stimulus artifact sequence corresponding to the current sampled signal sequence.

[0164] In practice, the system retrieves stimulus artifact data corresponding to the currently sampled signal sequence from the stimulus artifact sequence based on the stimulus phase reference point corresponding to the current phase synchronization period. For example, when the current sampled signal sequence corresponds to a certain stimulus phase position, the system extracts stimulus artifact data corresponding to the same stimulus phase position from the stimulus artifact sequence.

[0165] Furthermore, the system performs temporal matching on the stimulus artifact sequence based on the stimulus phase position corresponding to the current sampled signal sequence.

[0166] In practice, the system performs positional mapping of corresponding stimulus artifact data in the stimulus artifact sequence based on the sampling phase within the stimulus period corresponding to the current sampling point. For example, when the current sampling point corresponds to a certain stimulus phase position in the stimulus period, the system establishes a correspondence between the stimulus artifact data in the stimulus artifact sequence that corresponds to the same stimulus phase position and the current sampling data.

[0167] Further, as shown in Figure 12, the system calculates the corresponding point difference between the stimulus artifact sequence after time-series matching and the sampled signal sequence to generate the corresponding difference signal sequence, and then determines the difference signal sequence as the target deep brain field potential signal.

[0168] In practice, the system performs a difference operation on the stimulus artifact data corresponding to each sampling point in the sampled signal sequence. The difference operation formula is as follows: As described in the foregoing embodiments, it will not be repeated here.

[0169] The stimulus artifact sequence corresponds to periodic stimulus response components that recur in multiple phase synchronization cycles. After performing difference calculation, the periodic stimulus artifact components in the sampled signal sequence are eliminated. For example, the periodic high-amplitude artifact components corresponding to stimulus pulses have a repetitive structure between different phase synchronization cycles and can be canceled out by the stimulus artifact sequence. However, the neural responses, random fluctuation responses, or non-periodic EEG activities in the deep brain field potential signal do not have a repetitive structure and cannot be canceled out by the stimulus artifact sequence. Therefore, the system can eliminate periodic stimulus artifact components while retaining non-periodic deep brain field potential response components.

[0170] Furthermore, the system determines the target deep brain field potential signal based on the difference signal sequence after the elimination of stimulus artifacts.

[0171] In practice, the system uses the output of the difference calculation as the input of the target deep brain potential signal in subsequent deep brain potential analysis, neural state detection, or closed-loop neural modulation and control processes.

[0172] Compared to traditional fixed filtering methods, this embodiment achieves the removal of periodic stimulus artifact components under asynchronous sampling conditions by eliminating stimulus artifact differences based on the correspondence between stimulus phase positions, thereby improving the accuracy of target deep brain field potential signal recovery.

[0173] This embodiment, based on the above embodiment, further explains the process of re-establishing the electrical stimulation output phase reference according to the reset stimulation cycle count, as shown in Figure 13. The method for establishing a unified stimulation phase reference includes the following steps S181-S183:

[0174] S181: Determine the output time of the first stimulus pulse after restarting in each phase synchronization cycle as the unified stimulus phase reference point; S182: Based on the unified stimulus phase reference point, perform phase position correspondence on the stimulus output timing in different phase synchronization cycles; S183: Establish stimulus phase offset constraint relationship between different phase synchronization cycles based on the corresponding stimulus output timing.

[0175] In this embodiment, after each phase synchronization cycle ends, the system resets the stimulation cycle count and re-establishes the corresponding electrical stimulation output phase reference to maintain the phase consistency of stimulation artifacts between different phase synchronization cycles.

[0176] In practice, the system uses the start time of the stimulus output within each phase synchronization cycle as a unified phase reference point.

[0177] In practice, at the beginning of each phase synchronization cycle, the system determines the output time of the first stimulus pulse after restarting as the unified stimulus phase reference point corresponding to the current phase synchronization cycle. For example, the start time of the current phase synchronization cycle is denoted as... Then, within the current phase synchronization period, the output time of subsequent stimulation pulses will all be based on... As a unified stimulus phase reference, the stimulus outputs in different phase synchronization cycles can all establish corresponding stimulus phase structures based on the unified stimulus phase reference point.

[0178] Furthermore, the system limits the stimulus phase offset between different phase synchronization cycles to a preset range based on a unified stimulus phase reference point.

[0179] In practice, the system re-establishes a unified stimulus phase reference point for the next phase synchronization cycle after each phase synchronization cycle ends, thus limiting the cumulative phase drift generated during long-term asynchronous operation of the stimulus clock and the acquisition clock. For example, during continuous operation, the stimulus clock and the acquisition clock are driven by different oscillators, and a time offset may gradually occur between the stimulus output time and the sampling time. By periodically re-establishing a unified stimulus phase reference point, the system keeps the stimulus phase offset between different phase synchronization cycles within a preset range. For instance, the system can limit the stimulus phase offset generated between different phase synchronization cycles to within a single sampling cycle, preventing the cumulative stimulus phase drift from spreading continuously during long-term operation.

[0180] Furthermore, by limiting the stimulus phase offset between different phase synchronization periods, the system ensures that stimulus artifacts formed within different phase synchronization periods maintain the same phase distribution structure in the sampling sequence. For example, when a stimulus artifact peak corresponds to a specific stimulus phase position in the current phase synchronization period, the corresponding stimulus artifact peak in subsequent phase synchronization periods will still remain near the same stimulus phase region.

[0181] This embodiment establishes a periodic, unified stimulus phase reference point to limit the stimulus phase shift under long-term asynchronous operation conditions, thereby ensuring that stimulus artifacts in different phase synchronization cycles maintain a consistent phase distribution structure, improving the correspondence between stimulus artifacts in the same phase synchronization cycle, and enhancing the stimulus artifact removal effect.

[0182] Figure 14 is an example of an electrical stimulation artifact removal system based on periodic phase synchronization provided in an embodiment of this application.

[0183] The system is applied to the acquisition of deep brain field potential signals and the removal of stimulus artifacts during deep brain stimulation. Under the condition that the stimulation clock and the acquisition clock operate independently and asynchronously, the system can realize the phase alignment of stimulus artifacts, the generation of stimulus artifact sequences, and the removal of stimulus artifacts, so as to obtain the target deep brain field potential signal after the removal of stimulus artifacts.

[0184] The system in this embodiment is applied to the method described in the above embodiments. The system includes a stimulus output module 201, a signal acquisition module 202, a period synchronization module 203, a phase reconstruction module 204, an artifact generation module 205, and an artifact removal module 206.

[0185] The stimulation output module 201 is used to perform periodic electrical stimulation output on the target tissue according to the electrical stimulation signal generated by the stimulation clock.

[0186] In specific implementation, the stimulation output module 201 includes a stimulation clock generation unit 2012, a stimulation parameter control unit 2013, and a stimulation pulse output unit 2014.

[0187] Among them, the stimulation clock generation unit 2012 is used to generate the corresponding stimulation clock signal, the stimulation parameter control unit 2013 is used to configure the stimulation frequency, stimulation pulse width and stimulation amplitude according to the preset stimulation parameters, and the stimulation pulse output unit 2014 is used to control the stimulation pulse output time according to the stimulation clock and output periodic electrical stimulation signals to the target brain region 20.

[0188] Furthermore, the stimulation output module 201 can output stimulation pulses to the target tissue via an implanted stimulation electrode.

[0189] In this embodiment, the stimulation output module 201 and the signal acquisition module 202 operate with independent clock sources to achieve asynchronous timing control.

[0190] The signal acquisition module 202 is used to sample the response signal of the target tissue according to an acquisition clock that is independent of the stimulation clock, so as to obtain a sampled signal sequence.

[0191] In specific implementation, the signal acquisition module 202 includes an acquisition clock generation unit 2022, an analog front-end amplification unit 2023, an analog-to-digital conversion unit 2024, and a sampling buffer unit 2025. Specifically, the acquisition clock generation unit 2022 generates the acquisition clock, the analog front-end amplification unit 2023 amplifies the response signal generated by the target tissue with low noise, the analog-to-digital conversion unit 2024 performs continuous analog-to-digital conversion sampling according to the acquisition clock, and the sampling buffer unit 2025 buffers the generated sampling signal sequence.

[0192] Furthermore, since the acquisition clock is independent of the stimulus clock, there is no fixed synchronization relationship between the sampling time of the response signal and the output time of the stimulus pulse.

[0193] The period synchronization module 203 is used to perform electrical stimulation output in each phase synchronization cycle according to the set phase synchronization cycle, and to perform response signal sampling according to the acquisition clock.

[0194] In specific implementation, the period synchronization module 203 includes a period synchronization timing unit 2031, a stimulation period counting unit 2032, and a period synchronization triggering unit 2033.

[0195] Among them, the periodic synchronization timing unit 2031 is used to establish the corresponding phase synchronization period, the stimulation period counting unit 2032 is used to record the number of stimulation pulse outputs within the current phase synchronization period, and the periodic synchronization triggering unit 2033 is used to trigger the periodic phase synchronization operation after the end time of the phase synchronization period is reached.

[0196] Furthermore, within each phase synchronization cycle, the stimulation output module 201 continuously outputs stimulation pulses, and the signal acquisition module 202 continuously samples the response signal to form a sampling signal sequence corresponding to the current phase synchronization cycle.

[0197] The phase reconstruction module 204 is used to reset the stimulation cycle count when the phase synchronization period is reached, and to re-establish the phase reference of the electrical stimulation output based on the reset stimulation cycle count, so that the stimulation artifacts in different phase synchronization periods maintain the periodic phase consistency.

[0198] In specific implementation, the phase reconstruction module 204 includes a count clearing unit 2041, a timing reconstruction unit 2042, and a phase reference establishment unit 2043.

[0199] Among them, the count clearing unit 2041 is used to clear the stimulation cycle count after the end of the phase synchronization cycle, the timing reconstruction unit 2042 is used to regenerate the stimulation output timing based on the cleared stimulation cycle count, and the phase reference establishment unit 2043 is used to establish a new stimulation phase reference point based on the first stimulation pulse output time after restarting.

[0200] By using the above method, the cumulative phase drift between the stimulus output timing and the sampling timing can be limited, so that the stimulus artifacts in different phase synchronization periods can maintain a consistent phase distribution structure.

[0201] The artifact generation module 205 is used to generate a stimulus artifact sequence based on the sampled signal sequence within multiple phase synchronization cycles.

[0202] In specific implementation, the artifact generation module 205 includes a phase alignment unit 2051, a data arrangement unit 2052, and a moving average unit 2053.

[0203] The phase alignment unit 2051 is used to align the phase positions of the sampled signal sequences in multiple phase synchronization cycles according to the stimulus phase reference points corresponding to each phase synchronization cycle. The data arrangement unit 2052 is used to arrange the sampled data after phase alignment in chronological order. The moving average unit 2053 is used to perform moving average processing on the arranged sampled data to extract the periodic stimulus response components that recur in multiple phase synchronization cycles.

[0204] Furthermore, the artifact generation module 205 generates a corresponding stimulus artifact sequence based on the extracted periodic stimulus response components.

[0205] The artifact removal module 206 is used to remove stimulus artifacts from the sampled signal sequence based on the sampled signal sequence and the stimulus artifact sequence, so as to obtain the target deep brain field potential signal after the stimulus artifacts are removed.

[0206] In specific implementation, the artifact removal module 206 includes a timing matching unit 2061, a difference calculation unit 2062, and a signal output unit 2063.

[0207] The timing matching unit 2061 is used to perform timing matching on the stimulus artifact sequence according to the stimulus phase position corresponding to the current sampling signal. The difference calculation unit 2062 is used to calculate the difference between the stimulus artifact sequence after timing matching and the sampling signal sequence to generate a difference signal sequence. The signal output unit 2063 is used to output the target deep brain field potential signal after stimulus artifact removal according to the difference signal sequence.

[0208] Furthermore, the target deep brain field potential signal in this embodiment can be used in applications such as neural oscillation analysis, pathological state identification, closed-loop stimulation control, and brain-computer interface signal processing.

[0209] In this embodiment, since the system does not need to establish a fixed multiple relationship between the stimulation clock and the acquisition clock, the clock coupling between the stimulation output module 201 and the signal acquisition module 202 can be reduced.

[0210] Furthermore, through a periodic phase synchronization mechanism, this embodiment can maintain a stable phase structure of stimulus artifacts under asynchronous sampling conditions, thereby improving the accuracy of stimulus artifact sequence construction and the effect of stimulus artifact removal.

[0211] Other embodiments of this application will readily conceive of by those skilled in the art upon consideration of the specification and practice of the disclosure herein. This application is intended to cover any variations, uses, or adaptations of this application that follow the general principles of this application and include common knowledge or customary techniques in the art not disclosed herein. The specification and embodiments are to be considered exemplary only, and this application is not limited to the precise structures described above and shown in the accompanying drawings, and various modifications and changes can be made without departing from its scope.

Claims

1. A method for removing electrical stimulation artifacts based on periodic phase synchronization, characterized in that, include: The target tissue is periodically electrically stimulated based on the electrical stimulation signal generated by the stimulation clock; The response signal of the target tissue is sampled according to an acquisition clock that is independent of the stimulation clock to obtain a sampled signal sequence; Electrical stimulation output is performed within each phase synchronization cycle according to the set phase synchronization cycle, and response signal sampling is performed according to the acquisition clock. When the phase synchronization period is reached, the stimulation period count is reset, and the phase reference of the electrical stimulation output is re-established based on the reset stimulation period count, so that the stimulation artifacts in different phase synchronization periods keep the period phase consistent. A sampling signal sequence corresponding to multiple phase synchronization cycles is obtained. Based on the stimulus phase reference point corresponding to each phase synchronization cycle, the sampling signal sequence in the multiple phase synchronization cycles is phase-aligned. The sampling signal sequence after phase alignment is arranged in chronological order. A moving average processing is performed on the arranged sampling signal sequence to retain the periodic stimulus response components that recur in the multiple phase synchronization cycles. A corresponding stimulus artifact sequence is generated based on the periodic stimulus response components. Based on the sampled signal sequence and the stimulus artifact sequence, the stimulus artifacts in the sampled signal sequence are removed to obtain the target deep brain field potential signal after stimulus artifact removal.

2. The method according to claim 1, characterized in that, The step of performing electrical stimulation output within each phase synchronization cycle according to a set phase synchronization cycle includes: Based on the obtained preset phase synchronization period duration, a periodic synchronization window corresponding to the phase synchronization period duration is established; At the start of the periodic synchronization window, the stimulation cycle counting is started according to the stimulation clock, and the periodic electrical stimulation output is executed according to the set stimulation frequency and stimulation pulse width. During the execution of the periodic electrical stimulation output, the response signal of the target tissue is continuously sampled according to the acquisition clock to obtain the sampling signal sequence corresponding to the current periodic synchronization window. Within the periodic synchronization window, the number of stimulation pulse outputs is cumulatively counted, and the periodic position corresponding to the current stimulation output is determined based on the cumulative count result. After the end of the periodic synchronization window is reached, a periodic phase synchronization operation is triggered. By recalibrating the stimulus output phase, the cumulative phase drift of stimulus artifacts between different phase synchronization cycles is limited, so that the stimulus artifacts in different phase synchronization cycles maintain periodic phase consistency.

3. The method according to claim 1, characterized in that, When the phase synchronization period is reached, the stimulation cycle count is reset, and the phase reference of the electrical stimulation output is re-established based on the reset stimulation cycle count, including: After detecting that the current stimulus output has reached the end time of the corresponding phase synchronization period, the current stimulus pulse output is stopped, and the acquisition state of the current sampling signal sequence is maintained. The stimulation cycle counter corresponding to the current stimulus output is cleared to eliminate the accumulated count deviation in the previous phase synchronization cycle; The stimulation output timing is regenerated based on the zeroed stimulation cycle count, and the electrical stimulation output corresponding to the next phase synchronization cycle is started based on the regenerated stimulation output timing. The moment corresponding to the first stimulus pulse after restarting is taken as the new stimulus phase reference point, and the stimulus output phase corresponding to the next phase synchronization cycle is established according to the new stimulus phase reference point, so that the stimulus start phase between adjacent phase synchronization cycles remains consistent, thereby limiting the cumulative phase drift of stimulus artifacts between consecutive phase synchronization cycles and maintaining the periodic phase consistency of stimulus artifacts.

4. The method according to claim 1, characterized in that, The step of sampling the response signal of the target tissue according to an acquisition clock independent of the stimulation clock includes: The output frequency and output pulse width of the electrical stimulation signal are controlled according to the stimulation clock generated by the first clock source; The sampling frequency of the response signal is controlled by the acquisition clock generated by the second clock source; The corresponding stimulation output timing is established according to the stimulation clock, and the corresponding signal sampling timing is established according to the acquisition clock. During the electrical stimulation output process, stimulation pulse output is executed according to the stimulation output timing, and response signal sampling is executed according to the signal sampling timing, so that the stimulation output timing and the signal sampling timing run independently according to their respective clock cycles, so as to realize asynchronous timing control between electrical stimulation output and response signal acquisition.

5. The method according to claim 4, characterized in that, The asynchronous timing control between electrical stimulation output and response signal acquisition includes: During continuous stimulus output, response signal sampling data corresponding to different stimulus cycles are acquired; Based on the stimulation pulse output position corresponding to each response signal sampling data, establish the sampling data relationship corresponding to different stimulation phase positions; Based on the correspondence between the stimulus phase positions in different stimulus cycles, response signal sampling data covering the entire stimulus cycle is obtained to maintain the phase consistency of stimulus artifacts between different phase synchronization cycles.

6. The method according to claim 1, characterized in that, The step of performing a moving average processing on the arranged sampled signal sequence includes: Establish a sliding data window that contains sampling data from multiple phase synchronization cycles; The number of phase synchronization cycles participating in the moving average calculation is determined based on the preset window length; After acquiring new phase synchronization cycle sampling data, the latest phase synchronization cycle sampling data is added to the sliding data window, and the earliest phase synchronization cycle sampling data added to the sliding data window is removed. The average value is calculated for the sampled data corresponding to the same phase position within the sliding data window to generate an updated stimulus artifact sequence; The updated stimulus artifact sequence is used to track changes in stimulus artifact waveforms to improve the adaptability of the stimulus artifact removal process to changes in stimulus state.

7. The method according to claim 1, characterized in that, The step of removing stimulus artifacts from the sampled signal sequence based on the sampled signal sequence and the stimulus artifact sequence includes: Obtain the stimulus artifact sequence corresponding to the current sampled signal sequence; Based on the stimulus phase position corresponding to the current sampled signal sequence, the stimulus artifact sequence is time-matched; The stimulus artifact sequence after time-series matching is compared with the sampled signal sequence by calculating the corresponding point difference to generate the corresponding difference signal sequence. The periodic stimulus artifacts in the sampled signal sequence are eliminated based on the difference signal sequence, while the non-periodic deep brain field potential response components are retained. The difference signal sequence after the elimination of stimulus artifacts was determined as the target deep brain field potential signal.

8. The method according to claim 1, characterized in that, The step of re-establishing the phase reference of the electrical stimulation output based on the reset stimulation cycle count includes: The moment of the first stimulus pulse output after restarting within each phase synchronization cycle is determined as the unified stimulus phase reference point. Based on the unified stimulus phase reference point, phase position correspondence is performed on the stimulus output timing sequence in different phase synchronization cycles; Establish the stimulus phase offset constraint relationship between different phase synchronization cycles based on the corresponding stimulus output timing.

9. A system for removing electrical stimulation artifacts based on periodic phase synchronization, characterized in that, The system, applicable to the method of any one of claims 1-8, comprises: The stimulation output module is used to periodically electrically stimulate the target tissue according to the electrical stimulation signal generated by the stimulation clock; The signal acquisition module is used to sample the response signal of the target tissue according to an acquisition clock that is independent of the stimulation clock, so as to obtain a sampled signal sequence; The periodic synchronization module is used to perform electrical stimulation output in each phase synchronization cycle according to the set phase synchronization cycle, and to perform response signal sampling according to the acquisition clock. The phase reconstruction module is used to reset the stimulation cycle count when the phase synchronization period is reached, and to re-establish the phase reference of the electrical stimulation output based on the reset stimulation cycle count, so that the stimulation artifacts in different phase synchronization periods keep the cycle phase consistent. The artifact generation module is used to generate a sequence of stimulus artifacts based on the sampled signal sequence within multiple phase synchronization cycles. The artifact removal module is used to remove stimulus artifacts from the sampled signal sequence based on the sampled signal sequence and the stimulus artifact sequence, so as to obtain the target deep brain field potential signal after the stimulus artifacts are removed.

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