Sleep regulation and control system and method based on neurotransmitter and vascular power bidirectional coupling

Abstract

The invention belongs to the technical field of bioelectronic medicine, and provides a sleep regulation and control system and method based on neurotransmitter and vascular power bidirectional coupling, and the system comprises a neurotransmitter detection module which is configured to correct a detection voltage according to the change of the local temperature of a detection part, the concentration of noradrenaline is obtained in real time by combining feedback regulation of a detection voltage correction value; the blood vessel phase calculation module is configured to calculate the phase difference fed back by the blood vessel pulsation in combination with the blood vessel diameter change rate and the noradrenaline concentration; the stimulation signal generation module is configured to consider the obtained detection voltage correction value and the phase difference to construct a multi-mode stimulation signal generation equation; and the regulation and control module is configured to dynamically adjust parameters of the constructed multi-mode stimulation signal generation equation in combination with the noradrenaline concentration and the blood vessel state, obtain and analyze an electrophysiological signal, track the physiological signal and complete effective sleep regulation and control based on neurotransmitter and blood vessel dynamic bidirectional coupling.

Description

Technical Field

[0001] The present invention belongs to the field of bioelectronic medicine technology, and specifically relates to a sleep regulation system and method based on bidirectional coupling of neurotransmitters and vascular dynamics. Background Art

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

[0003] Transcranial electrical stimulation is an important method of non-invasive neuromodulation. 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 will be stimulated to generate electrical excitement and discharge to generate excitation current. The excitation current can effectively and directly stimulate most areas of the brain, directly or indirectly stimulate all deep brain nuclei to further change the level of neurotransmitters, affect EEG rhythms, and improve the connection between brain areas, thereby achieving the purpose of enhancing brain function and improving sleep quality.

[0004] Existing transcranial electrical stimulation mostly uses a single-parameter feedback system. However, the single-parameter feedback system cannot effectively capture the triangular coupling relationship between neurotransmitters, blood vessels and cerebrospinal fluid (CSF); traditional transcranial stimulation has difficulty penetrating the blood-brain barrier and thus affects 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 the local brain temperature changes caused by transcranial stimulation.

[0005] Therefore, how to develop a norepinephrine fluctuation-driven vasoconstriction mechanism and the material's neural activation-sleep regulation relationship is a difficult problem that needs to be solved urgently. Summary of the Invention

[0006] To address the above-mentioned issues, the present invention proposes a sleep regulation system and method based on bidirectional coupling of neurotransmitters and vascular dynamics. By real-time monitoring of the phase difference between norepinephrine fluctuations and vascular pulsation, accurate tracking of physiological signals can be achieved. The monitored physiological signals are combined to dynamically adjust the dual-target stimulation parameters to achieve effective sleep regulation.

[0007] According to some embodiments, a first solution of the present invention provides a sleep regulation system based on bidirectional coupling of neurotransmitters and vascular dynamics, which adopts the following technical solutions: A sleep regulation system based on bidirectional coupling of neurotransmitters and vascular dynamics, comprising: a neurotransmitter detection module configured to correct a detection voltage based on changes in the local temperature of a detection site, and to obtain norepinephrine concentration in real time by combining feedback adjustment of the detection voltage correction value; a vascular phase calculation module configured to calculate a phase difference of vascular pulsation feedback by combining the vascular diameter change rate and the norepinephrine concentration; a stimulation signal generation module configured to construct a multimodal stimulation signal generation equation taking into account the obtained detection voltage correction value and the vascular pulsation feedback phase difference; The control module is configured to dynamically adjust the parameters of the multimodal stimulation signal generation equation constructed by combining norepinephrine concentration and vascular state, obtain electrophysiological signals, analyze the obtained electrophysiological signals, track physiological signals, and complete sleep regulation based on the bidirectional coupling of neurotransmitters and vascular dynamics.

[0008] As a further technical limitation, in the neurotransmitter detection module, 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 to the microelectrode. Under the action of the applied scanning voltage, oxidation and reduction reactions occur on the microelectrode, and the norepinephrine concentration is analyzed based on the changes in the current-voltage curve.

[0009] It is important to note that the corresponding relationship between the current-voltage curve and the norepinephrine concentration is as follows: in cyclic voltammetry detection, the peak oxidation current (Ipeak) of the carbon fiber microelectrode is positively correlated with the NE concentration (C), and its quantitative relationship follows the formula Ipeak = k·C; where k is the sensitivity coefficient; a standard curve is established using the Nernst equation to achieve quantification of concentrations above the detection limit of 50nM, and electrode drift interference is eliminated through non-stimulation zero-point calibration every 30 minutes (error <5nM).

[0010] Furthermore, a three-level closed-loop control is used to implement feedback adjustment of the detection voltage correction value. Specifically, the scanning voltage is dynamically compensated based on local temperature changes, electrode drift is calibrated, and norepinephrine concentration is adjusted; the phase difference of vascular pulsation feedback is multimodally verified, and the voltage parameters are automatically calibrated when the phase difference of vascular pulsation feedback is lower than the phase difference threshold; and the coordinated regulation of temperature, current, and vascular dynamics is combined to complete the analysis of norepinephrine concentration.

[0011] As a further technical limitation, the phase difference of the vascular pulsation feedback ;in, is the delay parameter, is the change in blood vessel diameter during time t; for The change in norepinephrine concentration over time; is the change in norepinephrine concentration within time t; For time.

[0012] As a further technical limitation, before constructing the multimodal stimulation signal generation equation, the obtained vascular pulsation signal is subjected to Kalman filtering to eliminate respiratory or motion artifacts, obtain the vascular fluctuation signal after the motion artifacts are removed, and then calculate the phase difference of the vascular pulsation feedback.

[0013] As a further technical limitation, the constructed multimodal stimulation signal generation equation is: ;in, is the temperature-dependent gain coefficient; is the target concentration of norepinephrine; is the current concentration of norepinephrine; is the vascular coupling coefficient of norepinephrine concentration; is the phase difference of vascular pulsation feedback; is the overheat protection coefficient; is the change in local temperature of the detection area.

[0014] Furthermore, based on the constructed multimodal stimulation signal generation equation, the relationship between norepinephrine concentration, vascular phase difference and 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 vascular pulsation feedback is dynamically adjusted, and the parameters of the multimodal stimulation signal generation equation change. The vascular state is judged according to the parameter changes to achieve sleep regulation.

[0015] Furthermore, the target concentration of norepinephrine Affected by circadian rhythm compensation, combined with the expression level of biological clock genes to simulate physiological circadian rhythm, i.e. .

[0016] As a further technical limitation, in the process of analyzing the obtained electrophysiological signal, the stimulation mode and equation parameters of the multimodal stimulation signal are adjusted according to the vascular state; the vascular state is determined according to the vascular tension dynamic equation, and the vascular tension dynamic equation is ;in, is the real-time diameter of the blood vessel; is the maximum physiological limit diameter of blood vessels; is the minimum physiological limit diameter of blood vessels; is the norepinephrine concentration; The contraction rate is driven by norepinephrine; is the intrinsic vascular relaxation rate constant.

[0017] According to some embodiments, a second solution of the present invention provides a sleep regulation method based on bidirectional coupling of neurotransmitters and vascular dynamics, using the following technical solutions: A sleep regulation method based on bidirectional coupling of neurotransmitters and vascular dynamics, comprising: The detection voltage is corrected according to the change of the local temperature of the detection part, and the norepinephrine concentration is obtained in real time by combining the feedback adjustment of the detection voltage correction value; The phase difference of vascular pulsation feedback is calculated by combining the rate of change of vascular diameter and norepinephrine concentration; Considering the obtained detection voltage correction value and the vascular pulsation feedback phase difference, a multimodal stimulation signal generation equation is constructed; By combining the parameters of the multimodal stimulation signal generation equation constructed by dynamic adjustment of norepinephrine concentration and vascular state, electrophysiological signals are obtained, analyzed, and physiological signals are tracked to complete sleep regulation based on the bidirectional coupling of neurotransmitters and vascular dynamics.

[0018] Compared with the prior art, the present invention has the following beneficial effects: The present invention achieves precise tracking of physiological signals by real-time monitoring of the phase difference between norepinephrine fluctuations and vascular pulsations, adjusts the norepinephrine concentration through real-time feedback based on local temperature changes, captures and monitors physiological signals by establishing a triangular coupling relationship between neurotransmitters, blood vessels, and cerebrospinal fluid, and dynamically adjusts dual-target stimulation parameters based on the monitored physiological signals to achieve effective sleep regulation. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] The drawings constituting a part of the specification of this embodiment are used to provide a further understanding of this embodiment. The schematic embodiments and descriptions of this embodiment are used to explain this embodiment and do not constitute an improper limitation on this embodiment.

[0020] Figure 1 This is a structural block diagram of a sleep regulation system based on bidirectional coupling of neurotransmitters and vascular dynamics in Example 1 of the present invention; Figure 2 This is a flow chart of a sleep regulation method based on bidirectional coupling of neurotransmitters and vascular dynamics in Example 2 of the present invention. DETAILED DESCRIPTION

[0021] The present invention will be further described below with reference to the accompanying drawings and embodiments.

[0022] It should be noted that the following detailed descriptions are exemplary and intended to provide further explanation of the present invention. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which the present invention belongs.

[0023] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit the exemplary embodiments according to the present invention. As used herein, unless the context clearly indicates otherwise, the singular form is intended to include the plural form. In addition, it should be understood that when the terms "comprise" and / or "include" are used in this specification, they indicate the presence of features, steps, operations, devices, components and / or combinations thereof.

[0024] In the present invention, terms such as "upper", "lower", "left", "right", "front", "back", "vertical", "horizontal", "side", "bottom", etc. indicating directions or positional relationships are based on the directions or positional relationships shown in the accompanying drawings. They are relational words determined only for the convenience of describing the structural relationships of the various parts or elements of the present invention, and do not specifically refer to any part or element in the present invention, and should not be understood as limiting the present invention.

[0025] In the present invention, terms such as "fixed connection," "connected," and "connection" should be interpreted broadly to mean a fixed connection, an integral connection, or a detachable connection; a direct connection or an indirect connection through an intermediary. Relevant researchers or technicians in this field may determine the specific meanings of these terms in the present invention based on specific circumstances, and they should not be construed as limitations of the present invention.

[0026] In the absence of conflict, the embodiments of the present invention and the features thereof may be combined with each other.

[0027] Example 1 The first embodiment of the present invention introduces a sleep regulation system based on bidirectional coupling of neurotransmitters and vascular dynamics.

[0028] like Figure 1 A sleep regulation system based on bidirectional coupling of neurotransmitters and vascular dynamics is shown, comprising: a neurotransmitter detection module configured to correct a detection voltage based on changes in the local temperature of a detection site, and to obtain norepinephrine concentration in real time by combining feedback adjustment of the detection voltage correction value; a vascular phase calculation module configured to calculate a phase difference of vascular pulsation feedback by combining the vascular diameter change rate and the norepinephrine concentration; a stimulation signal generation module configured to construct a multimodal stimulation signal generation equation taking into account the obtained detection voltage correction value and the vascular pulsation feedback phase difference; The control module is configured to dynamically adjust the parameters of the multimodal stimulation signal generation equation constructed by combining norepinephrine concentration and vascular state, obtain electrophysiological signals, analyze the obtained electrophysiological signals, track physiological signals, and complete sleep regulation based on the bidirectional coupling of neurotransmitters and vascular dynamics.

[0029] This example utilizes a carbon fiber microelectrode array with a diameter of 7 μm and a spacing of 50 μm. Cyclic voltammetry (scan rate 400 V / s) is used to cause alternating oxidation and reduction reactions at the electrodes. The electrochemical reaction is detected by detecting the characteristic signals (e.g., oxidation peak current) generated by the reaction current-voltage curve.

[0030] The current peak in this example is positively correlated with the norepinephrine (NE) concentration. Concentration quantification can be achieved by establishing a standard curve (such as the Nernst equation). Its 50nM detection limit indicates that the system can stably identify signal changes above this concentration threshold. The corresponding relationship between concentration and signal follows Where k is the sensitivity coefficient and C is the concentration. Electrode drift interference was eliminated by combining a zero-point calibration without stimulation every 30 minutes (error control <5nM). The vascular phase calculation module was used to combine the rate of change in vascular diameter (ΔD) with the change in NE concentration (Δ[NE]), and the phase difference parameter was used to further verify the reliability of concentration detection.

[0031] It should be noted that this embodiment uses a carbon fiber microelectrode array to detect norepinephrine (NE) concentration and simultaneously collects blood vessel diameter change rate (ΔD / Δt) data; calculates the phase difference of blood vessel pulsation feedback within the sliding time window, and the time delay parameter It can be determined by cross-correlation analysis (usually 200-500ms); then the phase difference of 10 consecutive cycles of vascular pulsation feedback is Hilbert transformed to calculate the standard deviation σ of the phase difference of vascular pulsation feedback φ , when σ φ When the phase difference is less than 0.15rad, the neurovascular coupling is considered stable, and the confidence level of the NE concentration detection value is increased to more than 95%; if the phase difference confidence level is detected, the neurovascular coupling is considered stable. , the triple verification mechanism is automatically triggered: Re-perform the cyclic voltammetry scan (increase the scan rate to 600 V / s), Compare the similarity between the current vascular pulsation power spectrum (0.01-0.1Hz frequency band) and the reference spectrum, The detection voltage compensation was adjusted using a PID controller (Kp=0.8, Ki=0.05, Kd=0.1) until the phase difference parameter returned to the valid range; the error of NE concentration detection was reduced from ±12nM in single mode to ±5nM.

[0032] It should be noted that the potential of the electrode may change slowly during long-term use. Zero-point calibration can be used to correct the change in potential, that is, zero-point calibration is automatically performed every 30 minutes in a non-stimulation state to eliminate the error caused by electrode drift (the error in this embodiment is less than 5nM) and ensure the accuracy of the detection data.

[0033] In this example, the Doppler ultrasound signal is filtered through a Butterworth bandpass filter (0.1-5 Hz) to extract the vascular diameter change rate ΔD / Δt. The Butterworth filter has a flat frequency response within the passband. A fourth-order bandpass filter is designed using `butter(4, [0.1 5] / (fs / 2), 'bandpass')`. Zero-phase filtering is then performed on the raw vascular diameter signal `D_raw` using `filtfilt(b, a, D_raw)` to obtain the filtered signal `D_filtered`. The vascular diameter change rate ΔD / Δt is then extracted, removing interference from irrelevant frequency bands.

[0034] The phase difference of the blood vessel pulsation feedback in this embodiment is ;in, is the delay parameter, is the change in blood vessel diameter during time t; for The change in norepinephrine concentration over time; is the change in norepinephrine concentration within time t; For time.

[0035] It should be noted that, before constructing the multimodal stimulation signal generation equation, this embodiment performs Kalman filtering on the obtained vascular pulsation signal to eliminate respiratory or motion artifacts and obtain a vascular pulsation signal after the motion artifacts are removed; at the same time, the obtained norepinephrine concentration is denoised, and the phase difference of the vascular pulsation feedback is calculated by combining the processed vascular pulsation signal and the norepinephrine concentration.

[0036] This example uses dynamic time warping (DTW) to address the sampling rate difference between the norepinephrine concentration signal (10 kHz) and the vascular signal (100 Hz). Specifically, the 10:1 sampling rate difference between the NE signal (10 kHz sampling rate) and the Doppler vascular signal (100 Hz sampling rate) is addressed by downsampling each signal—one sample is taken every 1000 points for the NE signal and every 100 points for the vascular signal, bringing the sampling rates of both signals to a uniform 10 Hz. The dtw function is called with a time warping window width (Warping Window = 20). The dynamic programming algorithm is constrained to search for the optimal alignment path within a range of ±20 sampling points (corresponding to a span of ±2000 ms). Signal matching pairs are marked using the index ix, suppressing long-term phase shifts. The optimal alignment path index ix is ​​calculated and generated. The original NE signal is retimed based on this index, ultimately outputting the aligned_ne signal. By controlling the window parameters, 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 NE signals and vascular signals, and providing a high-precision time alignment basis for subsequent neurotransmitter-vascular coupling analysis.

[0037] It should be noted that this embodiment achieves 2-millisecond timing alignment by controlling the dynamic time warping window parameters. Specifically: in the error control stage, based on the 100-ms resolution of a single sampling point at a 10-Hz sampling rate, the window constraint compresses the local alignment error to ±2 sampling points (±20ms), and refines the timestamp through cubic spline interpolation, ultimately reducing the timing error to less than 2ms; the calculation delay is controlled at the 10-μs level through the FPGA hardware acceleration architecture (100-MHz clock + three-stage pipeline), ensuring that the theoretical error is highly consistent with the measured error (±1.8ms), providing a sub-millisecond time reference for vascular-neurotransmitter phase difference analysis.

[0038] In this embodiment, during the process of constructing the multimodal stimulation signal generation equation, feature extraction and screening are performed on the acquired norepinephrine concentration and vascular pulsation signals. Specifically, the difference between the maximum and minimum norepinephrine concentrations is calculated within a sliding time window to quantify the intensity of sympathetic nerve activity (e.g., a fluctuation amplitude of 600 nM within a 30-second window). A fast Fourier transform (FFT) is performed on the vascular signal to extract the peak frequency of the power spectrum in the 0.01-0.1 Hz frequency band (e.g., 0.04 Hz corresponds to the autonomic nerve rhythm). Simultaneously, the rate of change of vascular diameter is calculated (e.g., 0.5% change per second) using a fourth-order Butterworth bandpass filter (0.1-5 Hz). The standard deviation σ of the phase difference between the two signals is calculated using a Hilbert transform. φA 100th-order FIR filter was used to eliminate high-frequency noise. The resulting standard deviation was used to quantify the coupling between norepinephrine concentration and blood vessels. Feature importance (based on the Gini coefficient) was assessed using the random forest algorithm. Feature selection was achieved through the following steps: First, the Random Forest Regressor algorithm was imported to build a random forest regression model consisting of 100 decision trees. This model was applied to the feature matrix X_features and the target variable y_phase_diff for training. The Gini importance coefficient of each feature was extracted using the feature_importances_ attribute. Feature selection was performed by setting a threshold of 0.15, retaining only the subset of features with importance above this threshold. Experimental validation showed that this screening strategy improved the interpretability of the feature set by 40% compared to the pre-screening level, significantly improving the efficiency of neurovascular coupling analysis.

[0039] The filtered features directly drive the dynamic parameter adjustment of the multimodal stimulation signal generation equation, that is, the fluctuation amplitude is determined by [NE] target =300+50×sin(2πt / 24) adjusts the circadian rhythm compensation term; the power spectrum peak frequency controls the low-frequency pulse stimulation parameters (e.g., 0.1 Hz corresponds to a 500 μs pulse width); the phase difference standard deviation σ φ When <15°, the vascular coupling coefficient =0.1 / (1+5([NE]-200)), enhancing vascular synchronization. To optimize efficiency, a three-stage pipeline processing using an FPGA and a 100MHz clock speed increased the Kalman filter speed by 20 times (from 15ms to 0.7ms). Combined with dynamic parameter updates (such as the temperature gain coefficient a=0.05×(1+0.2(T-37))) and overload protection (activating cooling when [NE]>600nM), the system achieved a real-time performance of 98.3%, a 41% improvement over traditional methods.

[0040] The multimodal stimulation signal generation equation constructed in this embodiment is: ;in, is the temperature-dependent gain coefficient, which is used to reflect the effect of temperature on the inverse mass feedback; is the target concentration of norepinephrine; is the current concentration of norepinephrine; is the vascular coupling coefficient of norepinephrine concentration, which is used to reflect the vascular synchronization effect; is the phase difference of vascular pulsation feedback; It is the overheat protection coefficient, which takes effect when the temperature is too high; is the change in local temperature of the detection area.

[0041] In this embodiment, the coefficient dynamic adjustment rule is: , the temperature T increases, Increase, the adverse feedback effect is enhanced; , which is about norepinephrine concentration The S-shaped function, when When it approaches 200nM, The change is gentle, reflecting the vascular coupling and Nonlinear relationship; , only when the temperature changes Activates above 1°C to prevent overheating.

[0042] In this embodiment, when [NE] < 150nM, Supplement NE; when [NE]>600nM, use Cooler_Power = 0.5×([NE] - 600) for overload cooling to maintain NE concentration in the appropriate range; target concentration of norepinephrine Affected by circadian rhythm compensation, combined with the expression level of biological clock genes to simulate physiological circadian rhythm, i.e. .

[0043] The stimulation mode and equation parameters of the multimodal stimulation signal are adjusted according to the vascular state; the vascular state is determined according to the vascular tension dynamic equation, which is: ;in, is the real-time diameter of the blood vessel; is the maximum physiological limit diameter of blood vessels; is the minimum physiological limit diameter of blood vessels; is the norepinephrine concentration; The contraction rate is driven by norepinephrine; is the intrinsic vascular relaxation rate constant.

[0044] In this embodiment, the vascular state is determined in real time based on the vascular tension dynamic equation: when the real-time vascular diameter D decreases by ≥20% compared to the vascular diameter reference value (contraction state), Item Dominance ( , such as [NE]>450nM), the electrophysiological signal showed that the power of the 0.01-0.05Hz low-frequency oscillation increased by 3.2 times ( ) and 120ms phase delay, at this time triggering 0.1Hz / 500μs low-frequency stimulation, through the activation of α1 receptors to reduce the local temperature by 0.5℃ / min, while inhibiting glutamate release by 38% to prolong deep sleep; when D increases by ≥15% compared with the baseline value of blood vessel diameter (diastolic state), leading( , such as [NE] < 200nM), the signal shows a 2.5-fold increase in high-frequency power at 40-60Hz ( ) and phase-locked value PLV>0.85, high-frequency stimulation of 100 Hz × 1s increased NO release by 2.3 times and simultaneously increased the power of the prefrontal theta rhythm by 65% ​​to promote NREM sleep transition. The parameters were dynamically adjusted using the Q-learning algorithm (response speed 0.1 seconds) to maintain the standard deviation of vascular diameter fluctuations. (standard deviation of blood vessel diameter fluctuation baseline value 5%) and coupling index>0.85, ultimately increasing deep sleep duration from 72 minutes to 102 minutes and reducing the number of awakenings from 6.2 times / night to 2.5 times.

[0045] It should be noted that a Phase Locking Value (PLV) > 0.85 indicates that the phase synchronization of two signals (such as neural electrical activity and vascular pulsation) has reached a highly coupled state. Specifically, PLV quantifies the degree of synchronization by calculating the absolute value of the exponential mean of the phase difference between the two signals. Its value range is 0 to 1: 0 represents no statistical coupling, and 1 represents complete phase lock. When PLV>0.85, it indicates that the standard deviation of the phase difference σφ between neural activity and vascular dynamic parameters (such as changes in vascular diameter) is <15°. At this time, the system determines that the neurovascular coupling is in a stable state and can trigger high-frequency stimulation (such as 100Hz×1s) to enhance the power of gamma oscillations and maintain the standard deviation of vascular diameter fluctuations σ_D <3%. This high PLV value is used in the sleep regulation system to dynamically adjust the stimulation parameters to ensure that the deep sleep duration is extended by 42% to 102 minutes. It should be noted that a coupling index > 0.85 specifically quantifies the synchronization between neural activity and vascular dynamics. This index calculates the standard deviation of the phase difference (σφ) using a Hilbert transform. When σφ is < 0.15 rad (approximately 8.59°), the system determines that neurovascular coupling is stable. Specifically, the coupling index uses a phase lock value (PLV) algorithm, with values ​​ranging from 0 to 1 reflecting the degree of synchronization. A value above 0.85 indicates close phase alignment between neural activity (such as gamma oscillations) and vascular pulsations (such as the rate of diameter change ΔD / Δt). At this point, the system triggers 100Hz high-frequency stimulation to enhance NO release and increase the power of the prefrontal theta rhythm by 65%. This strong coupling results in a standard deviation of vascular diameter fluctuations, σ_D, less than 3% (from a baseline of 5%). Furthermore, dynamic parameter adjustments using a Q-learning algorithm ultimately resulted in a regulation effect that increased deep sleep duration from 72 minutes to 102 minutes.

[0046] The Verilog-based FPGA real-time computing architecture implements dynamic parameter adjustment through a three-stage pipeline (data acquisition → coefficient calculation → stimulus generation): α varies with temperature, with the gain increasing by 4% for every 1°C increase in temperature; β uses an S-shaped function to achieve a three-fold steep increase when NE > 200nM; γ is positively correlated with ΔT, and protection is activated when the temperature change rate exceeds 0.5°C / min. 、 and Directly affects the characteristics of electrophysiological signals: low-frequency stimulation (0.1Hz, 500μs) increases the power of 0.01-0.05Hz delta waves by 3.2 times ( ) and produced a 120ms phase delay. High-frequency stimulation (100Hz×1s) caused the power of 40-60Hzγ oscillation to increase by 2.5 times ( ) and the phase locking value PLV>0.85, β>0.05, the vascular-neural synchronization index reached 0.91±0.03. Physiological signal tracking uses multimodal analysis: Hilbert transform calculates the phase difference standard deviation ( Good coupling is determined), sliding window FFT (10s window length) is used to identify the characteristic frequency of vascular pulsation (systolic state) , diastolic state ), Kalman filter (delay < 0.7ms) predicts vascular status and adjusts parameters 50ms in advance. Sleep regulation is achieved through neurovascular coupling: vascular contraction ( ) 0.1Hz stimulation caused the NE concentration to decrease at a rate of 15nM / s, inhibiting the awakening signal of the locus coeruleus ( ); diastole ( ) 100Hz pulses increased NO release by 230% and enhanced the frontal lobe theta wave power by 65% ​​( ); NREM period maintains β = 0.05 ± 0.01 to make the standard deviation of vascular fluctuation , deep sleep is extended by 42% to 102 minutes, and the IEC60601 safety mechanism ensures that the device switches to limiting mode (80mA / 200μs) when the impedance change is greater than 5Ω / s The criterion for excessive vasoconstriction is a decrease of more than 20% in vascular diameter compared to the baseline value (i.e., a 20% decrease in diameter change D). At this point, intervention is triggered through a multimodal monitoring mechanism: real-time detection of neurotransmitter concentration ([NE]), phase difference of vascular pulsation feedback ( ) and local temperature (T). When [NE] rises abnormally and the phase delay exceeds the threshold, it automatically switches to low-frequency (0.1Hz), wide pulse width (500μs) electrical stimulation mode to enhance vasodilation effect; if the blood vessel diameter does not recover to more than 95% of the baseline value within 10 seconds, it starts This mechanism uses dynamic biosignal analysis and pre-set thresholds for dual verification, enabling precise identification and graded regulation of pathological vasoconstriction.

[0047] Example 2 The second embodiment of the present invention introduces a sleep regulation method based on bidirectional coupling of neurotransmitters and vascular dynamics.

[0048] like Figure 2 A sleep regulation method based on bidirectional coupling of neurotransmitters and vascular dynamics is shown, comprising: The detection voltage is corrected according to the change of the local temperature of the detection part, and the norepinephrine concentration is obtained in real time by combining the feedback adjustment of the detection voltage correction value; The phase difference of vascular pulsation feedback is calculated by combining the rate of change of vascular diameter and norepinephrine concentration; Considering the obtained detection voltage correction value and the vascular pulsation feedback phase difference, a multimodal stimulation signal generation equation is constructed; By combining the parameters of the multimodal stimulation signal generation equation constructed by dynamic adjustment of norepinephrine concentration and vascular state, electrophysiological signals are obtained, analyzed, and physiological signals are tracked to complete sleep regulation based on the bidirectional coupling of neurotransmitters and vascular dynamics.

[0049] 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 Example 1, and will not be repeated here.

[0050] The above description is merely a preferred embodiment of this embodiment and is not intended to limit this embodiment. Those skilled in the art will readily appreciate that this embodiment may be modified and varied in various ways. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of this embodiment shall be within the scope of protection of this embodiment.

Claims

1. A sleep regulation system based on bidirectional coupling of neurotransmitters and vascular dynamics, characterized in that: include: a neurotransmitter detection module configured to correct a detection voltage based on changes in the local temperature of a detection site, and to obtain norepinephrine concentration in real time by combining feedback adjustment of the detection voltage correction value; a vascular phase calculation module configured to calculate a phase difference of vascular pulsation feedback by combining the vascular diameter change rate and the norepinephrine concentration; a stimulation signal generation module configured to construct a multimodal stimulation signal generation equation taking into account the obtained detection voltage correction value and the vascular pulsation feedback phase difference; The control module is configured to dynamically adjust the parameters of the multimodal stimulation signal generation equation constructed by combining norepinephrine concentration and vascular state, obtain electrophysiological signals, analyze the obtained electrophysiological signals, track physiological signals, and complete sleep regulation based on the bidirectional coupling of neurotransmitters and vascular dynamics.

2. A sleep regulation system based on bidirectional coupling of neurotransmitters and vascular dynamics as described in claim 1, characterized in that: In the neurotransmitter detection module, 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 to the microelectrode. Under the action of the applied scanning voltage, oxidation and reduction reactions occur on the microelectrode, and the norepinephrine concentration is analyzed based on the changes in the current-voltage curve.

3. A sleep regulation system based on bidirectional coupling of neurotransmitters and vascular dynamics as described in claim 2, characterized in that: A three-level closed-loop control system is used to implement feedback adjustment of the detection voltage correction value. Specifically, the scanning voltage is dynamically compensated based on local temperature changes, electrode drift is calibrated, and norepinephrine concentration is adjusted. Multimodal verification of the phase difference of vascular pulsation feedback is performed, and the voltage parameters are automatically calibrated when the phase difference of vascular pulsation feedback is lower than the phase difference threshold. The norepinephrine concentration analysis is completed by combining the coordinated regulation of temperature, current, and vascular dynamics.

4. A sleep regulation system based on bidirectional coupling of neurotransmitters and vascular dynamics as described in claim 1, characterized in that: The phase difference of the vascular pulsation feedback ;in, is the delay parameter, is the change in blood vessel diameter during time t; for The change in norepinephrine concentration over time; is the change in norepinephrine concentration within time t; For time.

5. A sleep regulation system based on bidirectional coupling of neurotransmitters and vascular dynamics as claimed in claim 1, characterized in that: Before constructing the multimodal stimulation signal generation equation, the obtained vascular pulsation signal is processed by Kalman filtering to eliminate respiratory or motion artifacts, obtain the vascular fluctuation signal after motion artifact removal, and then calculate the phase difference of the vascular pulsation feedback.

6. A sleep regulation system based on bidirectional coupling of neurotransmitters and vascular dynamics as described in claim 1, characterized in that: The constructed multimodal stimulation signal generation equation is: ;in, is the temperature-dependent gain coefficient; is the target concentration of norepinephrine; is the current concentration of norepinephrine; is the vascular coupling coefficient of norepinephrine concentration; is the phase difference of vascular pulsation feedback; is the overheat protection coefficient; is the change in local temperature of the detection area.

7. A sleep regulation system based on bidirectional coupling of neurotransmitters and vascular dynamics as claimed in claim 6, characterized in that: Based on the constructed multimodal stimulation signal generation equation, the relationship between norepinephrine concentration, vascular phase difference and local temperature changes is obtained. That is, when the norepinephrine concentration decreases, the vascular coupling coefficient of norepinephrine concentration increases, and the phase difference of vascular pulsation feedback is dynamically adjusted. The parameters of the multimodal stimulation signal generation equation change, and the vascular state is judged according to the parameter changes to achieve sleep regulation.

8. A sleep regulation system based on bidirectional coupling of neurotransmitters and vascular dynamics as described in claim 6, characterized in that: The target concentration of norepinephrine Affected by circadian rhythm compensation, combined with the expression level of biological clock genes to simulate physiological circadian rhythm, i.e. .

9. The sleep regulation system based on bidirectional coupling of neurotransmitters and vascular dynamics as claimed in claim 1, characterized in that: In the process of analyzing the obtained electrophysiological signals, the stimulation mode and equation parameters of the multimodal stimulation signal are adjusted according to the vascular state; the vascular state is determined according to the vascular tension dynamic equation, which is: ;in, is the real-time diameter of the blood vessel; is the maximum physiological limit diameter of blood vessels; is the minimum physiological limit diameter of blood vessels; is the norepinephrine concentration; The contraction rate is driven by norepinephrine; is the intrinsic vascular relaxation rate constant.

10. A sleep regulation system based on bidirectional coupling of neurotransmitters and vascular dynamics, characterized in that: include: The detection voltage is corrected according to the change of the local temperature of the detection part, and the norepinephrine concentration is obtained in real time by combining the feedback adjustment of the detection voltage correction value; The phase difference of vascular pulsation feedback is calculated by combining the rate of change of vascular diameter and norepinephrine concentration; Considering the obtained detection voltage correction value and the vascular pulsation feedback phase difference, a multimodal stimulation signal generation equation is constructed; By combining the parameters of the multimodal stimulation signal generation equation constructed by dynamic adjustment of norepinephrine concentration and vascular state, electrophysiological signals are obtained, analyzed, and physiological signals are tracked to complete sleep regulation based on the bidirectional coupling of neurotransmitters and vascular dynamics.

Images