Sleep regulation system and method based on bidirectional coupling of neurotransmitters and vascular dynamics

Abstract

The application belongs to the technical field of bioelectronic medicine, and provides a sleep regulation system and method based on bidirectional coupling of neurotransmitters and vascular dynamics, which comprises: a neurotransmitter detection module configured to correct a detection voltage according to changes in local temperature of a detection site, to obtain a norepinephrine concentration in real time by combining feedback adjustment of the detection voltage correction value; a blood vessel phase calculation module configured to calculate a phase difference of vascular pulsation feedback by combining a blood vessel diameter change rate and the norepinephrine concentration; a stimulation signal generation module configured to consider the obtained detection voltage correction value and the phase difference, and to construct a multi-modal stimulation signal generation equation; and a regulation module configured to dynamically adjust parameters of the constructed multi-modal stimulation signal generation equation by combining the norepinephrine concentration and a blood vessel state, to obtain and analyze an electrophysiological signal, to track a physiological signal, and to complete effective sleep regulation based on bidirectional coupling of neurotransmitters and vascular dynamics.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of bio-electronic medical technology, and particularly relates to a sleep regulation system and method based on bidirectional coupling of neurotransmitters and vascular dynamics. BACKGROUND

[0002] The statements in this section merely provide background information related to the present application and do not necessarily constitute prior art.

[0003] Transcranial electrical stimulation is an important method of non-invasive neural regulation. By inputting the stimulation current of transcranial direct current stimulation (tDCS) or transcranial alternating current stimulation (tACS) into the superficial brain cortex, a large number of neurons in the nervous system are excited to generate an excitation current. By effectively directly stimulating most regions of the brain, all deep brain nuclei are directly or indirectly stimulated to further change the neurotransmitter level, affect the brain rhythm, and improve the connection between brain regions, so as to achieve the purpose of enhancing brain function and improving sleep quality.

[0004] Existing transcranial electrical stimulation mostly adopts a single-parameter feedback system. However, the single-parameter feedback system cannot effectively capture the triangular coupling relationship among neurotransmitters, blood vessels, and cerebrospinal fluid (CSF). Traditional transcranial stimulation cannot penetrate the blood-brain barrier, thereby affecting the release of norepinephrine (NE) in the locus coeruleus. Transcranial electrical stimulation can cause changes in brain temperature, and there is a lack of compensation mechanism for local brain temperature changes caused by transcranial stimulation.

[0005] Therefore, how to develop a norepinephrine fluctuation-driven blood vessel contraction mechanism and the relationship between neural activation and sleep regulation of the material is a difficult problem to be solved. SUMMARY

[0006] To solve the above problems, the present application provides a sleep regulation system and method based on bidirectional coupling of neurotransmitters and vascular dynamics. By monitoring the phase difference between norepinephrine fluctuation and blood vessel pulsation in real time, the physiological signals can be accurately tracked. Dynamic adjustment of the double-target stimulation parameters is combined with the monitored physiological signals to complete effective regulation of sleep.

[0007] According to some embodiments, the first aspect of the present application provides a sleep regulation system based on bidirectional coupling of neurotransmitters and vascular dynamics, which adopts the following technical solution:

[0008] A sleep regulation system based on bidirectional coupling of neurotransmitters and vascular dynamics comprises:

[0009] A neurotransmitter detection module configured to correct the detection voltage according to the change of the local temperature of the detection site, and to obtain the norepinephrine concentration in real time by combining the feedback adjustment of the detection voltage correction value.

[0010] a blood vessel phase calculation module configured to calculate a phase difference of the blood vessel pulsation feedback in combination with the blood vessel diameter change rate and the norepinephrine concentration;

[0011] a stimulation signal generation module configured to construct a multi-modal stimulation signal generation equation in consideration of the obtained detection voltage correction value and the blood vessel pulsation feedback phase difference;

[0012] a regulation module configured to dynamically adjust parameters of the constructed multi-modal stimulation signal generation equation in combination with the norepinephrine concentration and the blood vessel state, obtain an electrophysiological signal, analyze the obtained electrophysiological signal, track a physiological signal, and complete sleep regulation based on bidirectional coupling of neurotransmitters and blood vessel dynamics.

[0013] As a further technical limitation, in the process of obtaining the norepinephrine concentration in real time, a carbon fiber microelectrode array is used in combination with cyclic voltammetry to apply a linearly changing scanning voltage on the microelectrode, and oxidation and reduction reactions occur on the microelectrode under the action of the applied scanning voltage. The concentration of norepinephrine is analyzed according to the current-voltage curve change.

[0014] It should be noted that the correspondence between the current-voltage curve and the norepinephrine concentration is as follows: in the cyclic voltammetry detection, the oxidation peak current peak (Ipeak) of the carbon fiber microelectrode is positively correlated with the NE concentration (C), and the quantitative relationship follows the formula Ipeak = k·C; where k is the sensitivity coefficient; a standard curve is established through the Nernst equation to realize concentration quantification above the 50nM detection limit, and electrode drift interference is eliminated through zero-point calibration every 30 minutes (error <5nM).

[0015] Further, a three-level closed-loop control is used to realize feedback regulation of the detection voltage correction value. Specifically, the scanning voltage is dynamically compensated based on local temperature changes, the electrode drift is calibrated, and the norepinephrine concentration is adjusted; the phase difference of the blood vessel pulsation feedback is verified in multiple modes, and when the phase difference of the blood vessel pulsation feedback is lower than the phase difference threshold, the voltage parameter is automatically calibrated; in combination with the synergistic regulation among temperature, current, and blood vessel dynamics, the norepinephrine concentration is analyzed.

[0016] As a further technical limitation, the phase difference of the blood vessel pulsation feedback ; wherein, is a time delay parameter, is the blood vessel diameter change amount within t time; is the norepinephrine concentration change amount within t time; is the norepinephrine concentration change amount within t time; is t time.

[0017] As a further technical limitation, before constructing the multi-modal stimulation signal generation equation, the obtained blood vessel pulsation signal is subjected to Kalman filtering processing to eliminate respiratory or motion artifacts, to obtain a blood vessel fluctuation signal after motion artifact removal, and then the phase difference of the blood vessel pulsation feedback is calculated.

[0018] As a further technical limitation, the constructed multi-modal stimulation signal generation equation is ; wherein, is a temperature-dependent gain coefficient; is a target concentration of norepinephrine; is a current concentration of norepinephrine; is a vascular coupling coefficient of norepinephrine concentration; is a phase difference of the blood vessel pulsation feedback; is an overheat protection coefficient; is a change value of the local temperature of the detection site.

[0019] Further, based on the constructed multi-modal stimulation signal generation equation, the relationship between the norepinephrine concentration, the blood vessel phase difference, and the local temperature change is obtained, that is, when the norepinephrine concentration decreases, the vascular coupling coefficient of the norepinephrine concentration increases, the phase difference of the blood vessel pulsation feedback is dynamically adjusted, the parameters of the multi-modal stimulation signal generation equation change, the blood vessel state is judged according to the parameter change, and the sleep is regulated.

[0020] Further, the target concentration of norepinephrine is affected by the circadian rhythm compensation, and the physiological circadian rhythm is simulated by combining the biological clock gene expression level, that is, .

[0021] As a further technical limitation, in the process of analyzing the obtained electrophysiological signal, the stimulation mode and equation parameters of the multi-modal stimulation signal are adjusted according to the blood vessel state; the blood vessel state is determined according to a blood vessel tension dynamic equation, and the blood vessel tension dynamic equation is ; wherein, is a real-time diameter of the blood vessel; is a maximum blood vessel physiological limit diameter; is a minimum blood vessel physiological limit diameter; is a norepinephrine concentration; is a contraction rate driven by norepinephrine; is an inherent diastolic rate constant of the blood vessel.

[0022] According to some embodiments, a second aspect of the present application provides a sleep regulation method based on bidirectional coupling of neurotransmitters and blood vessel dynamics, which adopts the following technical solutions:

[0023] A sleep regulation method based on bidirectional coupling of neurotransmitters and vascular dynamics, comprising:

[0024] The detection voltage is corrected according to the change of the local temperature of the detection part, and the concentration of norepinephrine is obtained in real time through feedback adjustment of the detection voltage correction value;

[0025] The phase difference of vascular pulsation feedback is calculated in combination with the change rate of the vascular diameter and the concentration of norepinephrine;

[0026] The multi-modal stimulation signal generation equation is constructed by taking into account the obtained detection voltage correction value and the phase difference of vascular pulsation feedback;

[0027] The parameters of the constructed multi-modal stimulation signal generation equation are dynamically adjusted in combination with the concentration of norepinephrine and the vascular state, an electrophysiological signal is obtained, the obtained electrophysiological signal is analyzed, the physiological signal is tracked, and sleep regulation based on bidirectional coupling of neurotransmitters and vascular dynamics is completed.

[0028] Compared with the prior art, the beneficial effects of the present application are:

[0029] The present application realizes accurate tracking of physiological signals by real-time monitoring of the phase difference between norepinephrine fluctuation and vascular pulsation, real-time feedback adjustment of the concentration of norepinephrine in combination with local temperature change, physiological signal capture monitoring through construction of the triangular coupling relationship among neurotransmitters, blood vessels and cerebrospinal fluid, dynamic adjustment of double-target stimulation parameters in combination with the monitored physiological signals, and effective regulation of sleep. BRIEF DESCRIPTION OF DRAWINGS

[0030] The drawings constituting part of the present embodiment are used to provide further understanding of the present embodiment, and the illustrative embodiments of the present embodiment and their descriptions are used to explain the present embodiment and do not constitute undue limitation on the present embodiment.

[0031] Figure 1 A structural block diagram of a sleep regulation system based on bidirectional coupling of neurotransmitters and vascular dynamics in the present embodiment one;

[0032] Figure 2 A flowchart of a sleep regulation method based on bidirectional coupling of neurotransmitters and vascular dynamics in the present embodiment two. DETAILED DESCRIPTION

[0033] The present application will be further described below in combination with the drawings and embodiments.

[0034] It should be noted that the following detailed description is exemplary and is intended to provide further explanation of the present application. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as generally understood by those skilled in the art to which the present application belongs.

[0035] It should be noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of exemplary embodiments according to the invention. As used herein, the singular form is intended to include the plural form as well, unless the context clearly indicates otherwise. Furthermore, it should be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, devices, components, and / or combinations thereof.

[0036] In this invention, terms such as "upper," "lower," "left," "right," "front," "back," "vertical," "horizontal," "side," and "bottom" indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. These terms are used only to facilitate the description of the structural relationships of the various components or elements of this invention and do not specifically refer to any component or element in this invention. They should not be construed as limiting the invention.

[0037] In this invention, terms such as "fixed connection," "connected," and "linked" should be interpreted broadly, indicating a fixed connection, an integral connection, or a detachable connection; a direct connection or an indirect connection through an intermediate medium. Those skilled in the art can determine the specific meaning of these terms in this invention based on the specific circumstances, and they should not be construed as limitations on the invention.

[0038] Where there is no conflict, the embodiments and features in the embodiments of the present invention can be combined with each other.

[0039] Example 1

[0040] Embodiment 1 of this invention introduces a sleep regulation system based on bidirectional coupling of neurotransmitters and vasomotor dynamics.

[0041] like Figure 1 The sleep regulation system shown is based on bidirectional coupling of neurotransmitters and vasomotors, comprising:

[0042] The neurotransmitter detection module is configured to correct the detection voltage based on changes in the local temperature of the detection site, and to adjust the norepinephrine concentration in real time by combining the feedback of the detection voltage correction value.

[0043] The vascular phase calculation module is configured to calculate the phase difference of vascular pulsation feedback by combining the rate of change of vascular diameter and norepinephrine concentration.

[0044] The stimulation signal generation module is configured to construct a multimodal stimulation signal generation equation by taking into account the obtained detection voltage correction value and the vascular pulsation feedback phase difference.

[0045] The regulation module is configured to dynamically adjust parameters of a constructed multi-modal stimulation signal generation equation in combination with norepinephrine concentration and blood vessel state, to obtain an electrophysiological signal, analyze the obtained electrophysiological signal, track a physiological signal, and complete sleep regulation based on bidirectional coupling of neurotransmitters and blood vessel dynamics.

[0046] The embodiment utilizes a carbon fiber microelectrode array with a diameter of 7 μm and a pitch of 50 μm, and makes the electrodes alternately undergo oxidation and reduction reactions through cyclic voltammetry (scanning rate of 400 V / s), and obtains electrochemical reactions by detecting current-voltage curve characteristic signals (such as oxidation peak current value) generated in the reactions.

[0047] The current peak value in the embodiment is positively correlated with norepinephrine (NE) concentration, and concentration quantification can be realized by establishing a standard curve (such as a Nernst equation), and the 50 nM detection limit indicates that the system can stably identify signal changes above the concentration threshold. The corresponding relationship between the concentration and the signal follows ; wherein k is a sensitivity coefficient, and C is the concentration; the electrode drift interference is eliminated by combining the 30-minute non-stimulation zero-point calibration (error control <5 nM); the blood vessel diameter change rate (ΔD) is combined with the NE concentration change amount (Δ[NE]) through a blood vessel phase calculation module, and the reliability of the concentration detection is further verified by using a phase difference parameter.

[0048] It should be noted that the embodiment detects norepinephrine (NE) concentration by using a carbon fiber microelectrode array, and synchronously collects blood vessel diameter change rate (ΔD / Δt) data; the phase difference of the blood vessel pulsation feedback is calculated in a sliding time window, and the time delay parameter can be determined through cross-correlation analysis (usually 200-500 ms); the standard deviation σ φ of the phase difference of the blood vessel pulsation feedback is calculated by performing Hilbert transform on the phase difference of the blood vessel pulsation feedback of 10 consecutive cycles. φ When σ is less than 0.15 rad, it is determined that the neural-vascular coupling is stable, and the reliability of the NE concentration detection value is improved to more than 95%; if the phase difference confidence is detected, a triple verification mechanism is automatically triggered: the cyclic voltammetry scanning is re-executed (the scanning rate is improved to 600 V / s), the similarity of the current blood vessel pulsation power spectrum (0.01-0.1 Hz frequency band) and the reference spectrum is compared, the detection voltage compensation amount is adjusted through a PID controller (Kp=0.8, Ki=0.05, Kd=0.1) until the phase difference parameter returns to the effective range; and the error of the NE concentration detection is reduced from ±12 nM of a single mode to ±5 nM.

[0049] It should be noted that the potential of the electrode may change slowly during long-term use, and zero-point calibration can be used to correct the change of the potential, that is, zero-point calibration is automatically performed every 30 minutes in a non-stimulated state to eliminate errors caused by electrode drift (the error in the embodiment is less than 5nM), and ensure the accuracy of the detection data.

[0050] In the embodiment, the Doppler ultrasound signal is subjected to Butterworth band-pass filtering (0.1-5Hz) to extract the blood vessel diameter change rate ΔD / Δt; that is, the Butterworth filter has the characteristic that the frequency response is flat within the passband, a 4th-order band-pass filter is designed by `butter(4, [0.1 5] / (fs / 2), 'bandpass')`, then the original blood vessel diameter signal `D_raw` is subjected to zero-phase filtering by `filtfilt(b, a, D_raw)` to obtain the filtered signal `D_filtered`, and the blood vessel diameter change rate ΔD / Δt is extracted to remove irrelevant frequency band interference.

[0051] The phase difference of the blood vessel pulsation feedback in the embodiment ; wherein, is a time delay parameter, is the blood vessel diameter change amount within t time; is the blood vessel diameter change amount within t time; is the norepinephrine concentration change amount within t time; is t time.

[0052] It should be noted that, before constructing the multi-modal stimulation signal generation equation, the Kalman filtering process is performed on the obtained blood vessel pulsation signal to eliminate respiratory or motion artifacts, and the blood vessel pulsation signal after removal of motion artifacts is obtained; at the same time, the norepinephrine concentration obtained is subjected to denoising processing, and the phase difference of the blood vessel pulsation feedback is calculated in combination with the processed blood vessel pulsation signal and the norepinephrine concentration.

[0053] The embodiment adopts dynamic time warping (DTW) to process the difference in sampling rate between norepinephrine concentration signal (10 kHz) and blood vessel signal (100 Hz); specifically, for the 10:1 sampling rate difference between NE signal (10 kHz sampling rate) and Doppler blood vessel signal (100 Hz sampling rate), the NE signal and the blood vessel signal are respectively subjected to down-sampling processing - the NE signal takes one sample every 1000 points, and the blood vessel signal takes one sample every 100 points, so that the sampling rates of the two are unified to 10 Hz; the dtw function is called, the time warping window width (Warping Window = 20) is set, the dynamic programming algorithm is constrained to search for an optimal alignment path within a range of ±20 sampling points (corresponding to a span of ±2000 ms), the signal matching points are marked by index ix, long-term phase shift is suppressed, the optimal alignment path index ix is calculated and generated, and the original NE signal is rearranged in time based on the index, and finally the aligned_ne signal after alignment is output. By controlling the window parameter, the timing alignment error is limited to within 2 milliseconds, effectively solving the phase synchronization problem caused by the 10:1 sampling rate difference between the NE signal and the blood vessel signal, and providing a high-precision time alignment basis for subsequent neurotransmitter-blood vessel coupling analysis.

[0054] It should be noted that the embodiment realizes 2 millisecond timing alignment by controlling the dynamic time warping window parameter, specifically: in the error control stage, based on the resolution of 100 ms per single sampling point under a 10 Hz sampling rate, the window constraint compresses the local alignment error to ±2 sampling points (±20 ms), the time stamp is refined by cubic spline interpolation, and finally the timing error is reduced to within 2 ms; the calculation delay is controlled to be within 10 μs by the FPGA hardware acceleration architecture (100 MHz clock + three-stage pipeline), ensuring that the theoretical error is highly consistent with the measured error (±1.8 ms), and providing a sub-millisecond time reference for blood vessel-neurotransmitter phase difference analysis.

[0055] In the process of constructing the multi-modal stimulation signal generation equation, the obtained norepinephrine concentration and blood vessel pulsation signals are subjected to feature extraction and screening, specifically: the maximum and minimum difference of norepinephrine concentration is calculated in a sliding time window, and the sympathetic nerve activity intensity is quantified (such as a fluctuation amplitude of 600 nM within a 30 second window); the blood vessel signal is subjected to fast Fourier transform (FFT), and the power spectrum peak frequency of the 0.01-0.1 Hz frequency band is extracted (such as 0.04 Hz corresponding to autonomic nervous rhythm); the blood vessel diameter change rate is calculated by 4thorder Butterworth band-pass filtering (0.1-5 Hz) (such as 0.5% change per second); the standard deviation σ of the phase difference between the two signals is calculated by Hilbert transform φ, the 100th order FIR filter is used to eliminate high-frequency noise, and the standard deviation is used to quantify the coupling degree of norepinephrine concentration and blood vessels, and the feature importance is evaluated by the random forest algorithm (based on Gini coefficient); the feature selection is realized by the following steps: first, the Random ForestRegressor algorithm is imported, and a random forest regression model containing 100 decision trees is established. After the model is applied to the feature matrix X_features and the target variable y_phase_diff for training, the Gini importance coefficient of each feature is extracted by using the feature_importances_ attribute. By setting the threshold value 0.15, only the feature subset with importance higher than the threshold value is retained. Experimental verification shows that this screening strategy improves the interpretability index of the feature set by 40% compared with before screening, and significantly optimizes the neural-vascular coupling analysis efficiency.

[0056] The screened features directly drive the dynamic parameter adjustment of the multi-modal stimulation signal generation equation, that is, the fluctuation amplitude is adjusted by [NE] target =300+50×sin(2πt / 24) to adjust the circadian rhythm compensation term; the power spectrum peak frequency controls the low-frequency pulse stimulation parameters (such as 0.1Hz corresponding to 500μs pulse width); the phase difference standard deviation σ φ <15°, the vascular coupling coefficient =0.1 / (1+e -5([NE]-200 )) increases, enhancing the regulation of vascular synchrony. In terms of optimization efficiency, a three-stage pipeline processing with 100MHz clock is realized by FPGA, which improves the Kalman filtering speed by 20 times (time consumption 15ms→0.7ms), combined with dynamic parameter updating (such as temperature gain coefficient a=0.05×(1+0.2(T-37))) and overload protection ([NE]>600nM activates cooling), finally realizes the real-time index of 98.3%, which is improved by 41% compared with the traditional method.

[0057] The multi-modal stimulation signal generation equation constructed in this embodiment is ; wherein, is a temperature-dependent gain coefficient, which reflects the influence of temperature on the inverse feedback; is the target concentration of norepinephrine; is the current concentration of norepinephrine; is the vascular coupling coefficient of norepinephrine concentration, which embodies the role of vascular synchrony; is the phase difference of vascular pulsation feedback; is the overheat protection coefficient, which works when the temperature is too high; is the change value of the local temperature of the detection site.

[0058] In this embodiment, the coefficient dynamic adjustment rule is As temperature T rises, As the volume increases, the adverse mass feedback effect is enhanced; It's about norepinephrine concentration. The S-shaped function, when When it approaches 200 nM, The changes are gradual, reflecting vascular coupling and Nonlinear relationship; Only when temperature changes Activates above 1°C to prevent overheating.

[0059] In this embodiment, when [NE] < 150 nM, by Supplement NE; when [NE] > 600 nM, perform overload cooling with Cooler_Power = 0.5 × ([NE] - 600) to maintain NE concentration within a suitable range; target concentration of norepinephrine. Influenced by circadian rhythm compensation, and combined with the expression level of biological clock genes to simulate physiological circadian rhythms, that is... .

[0060] The stimulation mode and equation parameters of the multimodal stimulation signal are adjusted according to the vascular state; the vascular state is determined based on the vascular tension dynamic equation, which is as follows: ;in, This refers to the real-time diameter of the blood vessel. This represents the maximum physiological limit diameter of blood vessels. This is the minimum physiological limit diameter of the blood vessel; This refers to the concentration of norepinephrine. The rate of contraction driven by norepinephrine; is the intrinsic vasodilation rate constant of the blood vessel.

[0061] In this embodiment, the vascular state is determined in real time based on the dynamic equation of vascular tension: when the real-time vascular diameter D decreases by ≥20% compared to the baseline vascular diameter (contraction state), The item is superior ( (e.g., [NE]>450nM), the electrophysiological signal shows a 3.2-fold increase in the power of low-frequency oscillations at 0.01-0.05Hz. A 120ms phase delay triggers a 0.1Hz / 500μs low-frequency stimulus, which activates α1 receptors, causing a 0.5℃ / min decrease in local temperature and inhibiting glutamate release by 38% to prolong deep sleep. When D increases by ≥15% (diastolic state) compared to the baseline value of blood vessel diameter, leading( (e.g., [NE] < 200nM), the signal exhibits a 2.5-fold increase in high-frequency power at 40-60Hz. ) and a phase locking value (PLV) > 0.85, the system triggers 100Hz high-frequency stimulation to increase NO release by 2.3 times and simultaneously enhances prefrontal θ rhythm power by 65% to promote NREM sleep transition. Through the Q-learning algorithm, the system dynamically adjusts parameters (response speed 0.1 seconds) to maintain the standard deviation of the vessel diameter fluctuation (standard deviation of the vessel diameter fluctuation reference value 5%) and the coupling index > 0.85, and finally increases the deep sleep time from 72 minutes to 102 minutes and reduces the number of awakenings from 6.2 times / night to 2.5 times.

[0062] It should be noted that the phase locking value (PLV) > 0.85 indicates that the phase synchronization of two signals (such as neural electrical activity and blood vessel pulsation) reaches a high coupling state. Specifically, PLV quantifies the degree of synchronization by calculating the exponential average absolute value of the phase difference between the two signals, with a value range of 0 to 1: 0 represents no statistical coupling, and 1 indicates complete phase locking. When PLV > 0.85, it indicates that the phase difference standard deviation σφ between neural activity and vascular dynamics parameters (such as changes in vessel diameter) is < 15°, at which point the system determines that the neural-vascular coupling is in a stable state, and triggers high-frequency stimulation (such as 100Hz x 1s) to enhance γ oscillation power and maintain the standard deviation of the vessel diameter fluctuation σ_D < 3%. This high PLV value is used in the sleep regulation system to dynamically adjust stimulation parameters, ensuring that the deep sleep time is extended by 42% to 102 minutes

[0063] It should be noted that the coupling index > 0.85 specifically refers to a quantitative indicator of the synchronization between neural activity and vascular dynamics parameters. This index calculates the phase difference standard deviation (σφ) through Hilbert transform, and when σφ < 0.15 rad (about 8.59°), the system determines that the neural-vascular coupling is in a stable state. Specifically, the coupling index uses the phase locking value (PLV) algorithm, with a value range of 0-1 reflecting the degree of synchronization: above 0.85 indicates that the phase relationship between neural electrical activity (such as γ oscillation) and blood vessel pulsation (such as diameter change rate ΔD / Δt) is highly consistent, at which point the system triggers 100Hz high-frequency stimulation to enhance NO release and increase prefrontal θ rhythm power by 65%. This strong coupling state makes the standard deviation of the vessel diameter fluctuation σ_D < 3% (reference value 5%), and through the Q-learning algorithm, the system dynamically adjusts parameters to ultimately achieve the regulation effect of increasing the deep sleep time from 72 minutes to 102 minutes.

[0064] ​The Verilog-based FPGA real-time computing architecture realizes dynamic parameter adjustment through a three-stage pipeline (data acquisition → coefficient calculation → stimulus generation): α varies with temperature, and the gain increases by 4% for every 1℃ increase in temperature; β is realized through an S-shaped function, which increases by 3 times when NE>200nM; γ is positively correlated with ΔT, and is activated when the temperature change rate is >0.5℃ / min; 、 and directly affects the characteristics of electrophysiological signals: low-frequency stimulation (0.1Hz, 500μs) increases the δ wave power in the range of 0.01-0.05Hz by 3.2 times ( ) and causes a 120ms phase delay, and high-frequency stimulation (100Hz×1s) increases the γ oscillation power in the range of 40-60Hz by 2.5 times ( ) and the blood vessel-nerve synchrony index reaches 0.91±0.03 when β>0.05. The physiological signal tracking adopts multi-modal analysis: the Hilbert transform calculates the phase difference standard deviation ( to determine good coupling), the sliding window FFT (10s window length) identifies the characteristic frequency of blood vessel pulsation (systole , diastole ), and the Kalman filter (delay <0.7ms) predicts the blood vessel state and adjusts the parameters 50ms in advance. Sleep regulation is achieved through nerve-blood vessel coupling: 0.1Hz stimulation during the blood vessel contraction period ( ) reduces the NE concentration at a rate of 15nM / s, inhibiting the locus coeruleus arousal signal ( ); 100Hz pulse during the diastolic period ( ) increases NO release by 230% and enhances the frontal lobe θ wave power by 65% ( ); maintaining β=0.05±0.01 during NREM period reduces the standard deviation of blood vessel fluctuation , and deep sleep is prolonged by 42% to 102 minutes, while the IEC60601 safety mechanism ensures that when the impedance change is greater than 5Ω / s, it switches to the limiting mode (80mA / 200μs)

[0065] The criterion for determining excessive blood vessel contraction is that the blood vessel diameter decreases by more than 20% compared to the blood vessel diameter baseline value (i.e., the diameter change D decreases by 20%); at this time, the intervention is triggered through a multi-modal monitoring mechanism: real-time detection of neurotransmitter concentration ([NE]), phase difference feedback of blood vessel pulsation ( ), and local temperature (T), when [NE] abnormally increases and the phase delay exceeds the threshold, it automatically switches to low-frequency (0.1Hz), wide-pulse-width (500μs) electrical stimulation mode to enhance the blood vessel dilation effect; if it does not recover to more than 95% of the blood vessel diameter baseline value within 10 seconds, it starts The receptor agonist (such as salbutamol) is locally perfused for drug intervention. The judgment mechanism realizes accurate identification and hierarchical regulation of pathological vasoconstriction through double verification of dynamic biological signal analysis and preset threshold.

[0066] Embodiment two

[0067] Embodiment two of the present application introduces a sleep regulation method based on bidirectional coupling of neurotransmitters and vascular dynamics.

[0068] As Figure 2 shown in a sleep regulation method based on bidirectional coupling of neurotransmitters and vascular dynamics, comprising:

[0069] According to the change of the local temperature of the detection part, the detection voltage is corrected, and the norepinephrine concentration is obtained in real time by combining the feedback adjustment of the detection voltage correction value;

[0070] Combined with the blood vessel diameter change rate and the norepinephrine concentration, the phase difference of the vascular pulsation feedback is calculated;

[0071] Considering the obtained detection voltage correction value and the vascular pulsation feedback phase difference, a multi-modal stimulation signal generation equation is constructed;

[0072] Combined with the norepinephrine concentration and the vascular state, the parameters of the constructed multi-modal stimulation signal generation equation are dynamically adjusted to obtain an electrophysiological signal, the obtained electrophysiological signal is analyzed, the physiological signal is tracked, and the sleep regulation based on bidirectional coupling of neurotransmitters and vascular dynamics is completed.

[0073] The detailed steps are the same as the working principle of the sleep regulation system based on bidirectional coupling of neurotransmitters and vascular dynamics provided in embodiment one, and will not be repeated here.

[0074] The above only describes the preferred embodiments of the present application and is not intended to limit the present application. For those skilled in the art, the present application can have various modifications and changes. Any modification, equivalent replacement, improvement, etc. made within the spirit and principles of the present application shall be included in the protection scope of the present application.

Claims

1. A sleep regulation system based on bidirectional coupling of neurotransmitters and vascular dynamics, characterized in that, The method comprises the following steps: A neurotransmitter detection module is configured to correct the detection voltage according to the change of the local temperature of the detection site, and to obtain the norepinephrine concentration in real time by combining the feedback adjustment of the detection voltage correction value; a blood vessel phase calculation module configured to calculate a phase difference of the blood vessel pulsation feedback in combination with the blood vessel diameter change rate and the norepinephrine concentration; wherein the phase difference of the blood vessel pulsation feedback ; wherein, is a time delay parameter, is a blood vessel diameter change amount within a time t; is a blood vessel diameter change amount within a time t; is a norepinephrine concentration change amount within a time t; is a time. A stimulation signal generation module is configured to construct a multi-modal stimulation signal generation equation by considering the obtained detection voltage correction value and the phase difference of the vascular pulsation feedback; The regulation module is configured to dynamically adjust parameters of the constructed multi-modal stimulation signal generation equation in combination with norepinephrine concentration and blood vessel state, obtain an electrophysiological signal, analyze the obtained electrophysiological signal, track a physiological signal, and complete sleep regulation based on bidirectional coupling of neurotransmitters and blood vessel dynamics; wherein the constructed multi-modal stimulation signal generation equation is ; wherein, is a temperature-dependent gain coefficient; is a target concentration of norepinephrine; is a current concentration of norepinephrine; is a blood vessel coupling coefficient of norepinephrine concentration; is a phase difference of blood vessel pulsation feedback; is an over-temperature protection coefficient; is a change value of the local temperature of the detection part.

2. The sleep regulation system based on bidirectional coupling of neurotransmitters and vascular dynamics according to claim 1, characterized in that, In the neurotransmitter detection module, during the process of obtaining the norepinephrine concentration in real time, a carbon fiber microelectrode array is used, and a cyclic voltammetry method is used to apply a scanning voltage with a linear change on the microelectrode. Under the action of the applied scanning voltage, oxidation and reduction reactions occur on the microelectrode. The concentration of norepinephrine is analyzed according to the change of the current-voltage curve.

3. The sleep regulation system based on bidirectional coupling of neurotransmitters and vascular dynamics according to claim 2, characterized in that, The feedback adjustment of the detection voltage correction value is realized by using a three-level closed-loop control. Specifically, the scanning voltage is dynamically compensated based on the local temperature change, the electrode drift is calibrated, and the norepinephrine concentration is adjusted. The phase difference of the vascular pulsation feedback is verified in multiple modes. When the phase difference of the vascular pulsation feedback is lower than the phase difference threshold, the voltage parameter is automatically calibrated. The analysis of the norepinephrine concentration is completed by combining the synergistic adjustment among temperature, current and vascular dynamics.

4. The sleep regulation system based on bidirectional coupling of neurotransmitters and vascular dynamics of claim 1, wherein, Before constructing the multi-modal stimulation signal generation equation, the obtained vascular pulsation signal is processed by Kalman filtering to eliminate respiratory or motion artifacts, and the vascular fluctuation signal after removing the motion artifacts is obtained. Then, the phase difference of the vascular pulsation feedback is calculated.

5. The sleep regulation system based on bidirectional coupling of neurotransmitters and vasodynamics according to claim 1, characterized in that, Based on the constructed multi-modal stimulation signal generation equation, the relationship among the norepinephrine concentration, the vascular phase difference and the local temperature change is obtained. When the norepinephrine concentration decreases, the vascular coupling coefficient of the norepinephrine concentration increases, the phase difference of the vascular pulsation feedback is dynamically adjusted, the parameters of the multi-modal stimulation signal generation equation change, the vascular state is judged according to the parameter change, and the sleep is regulated.

6. The sleep regulation system based on bidirectional coupling of neurotransmitters and vasodynamics according to claim 1, characterized in that, The target concentration of said noradrenaline Influenced by the circadian compensation, the physiological circadian rhythm is simulated in combination with the expression level of the biological clock gene, i.e. .

7. The sleep regulation system based on bidirectional coupling of neurotransmitters and vasodynamics according to claim 1, characterized in that, In the process of analyzing the obtained electrophysiological signals, the stimulation mode and equation parameters of the multi-modal stimulation signals are adjusted according to a blood vessel state; the blood vessel state is determined according to a blood vessel tension dynamic equation, and the blood vessel tension dynamic equation is ; wherein, is a blood vessel real-time diameter; is a maximum blood vessel physiological limit diameter; is a minimum blood vessel physiological limit diameter; is a norepinephrine concentration; is a norepinephrine-driven contraction rate; is an inherent diastolic rate constant of the blood vessel.

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