CN-121338248-B - Implantable closed-loop nerve stimulation system and method for regulating and controlling stimulation parameters thereof

CN121338248BCN 121338248 BCN121338248 BCN 121338248BCN-121338248-B

Abstract

The application provides an implantable closed-loop nerve stimulation system and a regulation and control method of stimulation parameters thereof, wherein the regulation and control method comprises the steps of carrying out impedance measurement by applying double-frequency test currents to a plurality of electrodes to obtain a first complex impedance signal; the method comprises the steps of obtaining three-dimensional space impedance gradients based on space coordinates and corresponding impedance values of each electrode in a plurality of electrodes, regulating and controlling stimulation parameters of electric stimulation pulses according to the three-dimensional space impedance gradients and a first impedance change rate determined based on first complex impedance signals, carrying out impedance measurement in a first time period after the electric stimulation pulses are applied to obtain second complex impedance signals, obtaining first local field potential signals of areas where the plurality of electrodes are located in the first time period, and calibrating the regulated stimulation parameters when the second complex impedance signals meet a first condition and/or the first local field potential signals meet a second condition.

Inventors

ZHAO GUOGUANG
CAO PENG
SHAN YONGZHI

Assignees

首都医科大学宣武医院
杭州诺为医疗技术有限公司

Dates

Publication Date: 20260505
Application Date: 20251218

Claims (9)

1. An implantable closed-loop nerve stimulation system, comprising: A plurality of electrodes implanted intracranially; The dual-frequency impedance measurement circuit is used for applying dual-frequency test current to the plurality of electrodes and collecting response voltage before applying the electric stimulation pulse to the plurality of electrodes to generate a first complex impedance signal, and applying the dual-frequency test current to the plurality of electrodes again and collecting response voltage within a first time period after the end of the electric stimulation pulse to generate a second complex impedance signal; The local field potential recording circuit is used for synchronously collecting first local field potential signals of the areas where the plurality of electrodes are located in the first time period after the electric stimulation pulse is ended; The processing module is used for processing the first complex impedance signal to obtain a first impedance change rate; The spatial gradient calculation module is used for obtaining a three-dimensional spatial impedance gradient based on the spatial coordinates of each electrode and the corresponding impedance value, wherein the spatial coordinates of the plurality of electrodes are prestored in the storage unit; The stimulation parameter regulation and control module is used for regulating and controlling the stimulation parameters of the electric stimulation pulse based on the first impedance change rate and the three-dimensional space impedance gradient; The nerve stimulation driving circuit is used for outputting electric stimulation pulses to the plurality of electrodes according to the regulated stimulation parameters; And the calibration module is used for determining that the second complex impedance signal meets a first condition and/or calibrating the regulated stimulation parameter when the first local field potential signal meets a second condition.
2. The implantable closed-loop neurostimulation system of claim 1, wherein the dual-frequency impedance measurement circuit and the neurostimulation driving circuit are hardware circuits that are independent of each other.
3. The implantable closed-loop neurostimulation system of claim 1 or 2, the stimulation parameter modulation module being specifically configured for: regulating the stimulation current intensity of the electric stimulation pulse based on the first impedance change rate; Regulating and controlling the relative phase difference of the electric stimulation pulses between the plurality of electrodes based on the three-dimensional space impedance gradient; The regulated stimulation current intensity I is obtained by the following formula: , Wherein I 0 is the preset reference stimulus current intensity; The absolute value of the first impedance change rate is expressed in omega/s, theta 1 is a trigger threshold value of the impedance change rate, k1 is a gain coefficient, the value is greater than 0, gamma 1 is a sensitivity factor, the value is greater than 0, and tan h is # ) As a hyperbolic tangent function; The relative phase difference after regulation is obtained by the following formula: , Wherein delta is ij K2 is a phase scaling factor, and the value range is between 0.5 and 2; Is a position vector directed from electrode i to electrode j; is a three-dimensional space impedance gradient vector, Is that Is used for the mold length of the mold, Is that Is a die length of the die.
4. The implantable closed loop nerve stimulation system according to claim 1 or 2, wherein the first complex impedance signal and/or the second complex impedance signal R (t) is obtained by the following formula: , Wherein R LF (t) is low-frequency real part impedance, X HF (t) is high-frequency imaginary part impedance, the low frequency is 1 to 10 kHz, the high frequency is 50 to 200 kHz, alpha and beta are preset weight coefficients, and alpha+beta=1; the calibration module is specifically configured to adjust the stimulus current intensity of the next electrical stimulation pulse by adjusting the weight coefficient α corresponding to the low-frequency real part impedance and the weight coefficient β corresponding to the high-frequency imaginary part impedance, or by adjusting the trigger threshold θ 1 of the impedance change rate.
5. The implantable closed-loop neurostimulation system of claim 4, wherein the calibration module, when adjusting the weight coefficient α corresponding to the low-frequency real impedance and the weight coefficient β corresponding to the high-frequency imaginary impedance, is specifically configured to: The weight coefficient alpha corresponding to the low-frequency real part impedance is adjusted by delta alpha, and the weight coefficient beta corresponding to the high-frequency imaginary part impedance is adjusted by delta beta, wherein the value range of the adjusted weight coefficient alpha is between 0.6 and 0.9, and the value range of the adjusted weight coefficient beta is between 0.1 and 0.4; A trigger threshold θ 1 for adjusting the rate of change of impedance, comprising: And (3) downwards adjusting the triggering threshold value theta 1 of the impedance change rate by delta theta, wherein the value of the delta theta is larger than 0, and the adjusted theta 1 is larger than or equal to 0.2 omega/s.
6. The implantable closed loop nerve stimulation system according to claim 1 or 2, wherein the second complex impedance signal satisfies a first condition comprising a ratio of an absolute value of a second impedance change rate to an absolute value of the first impedance change rate being greater than a first threshold, wherein the second impedance change rate is obtained by sliding window filtering differentiation of the second complex impedance signal; The first local field potential signal satisfies a second condition comprising a power ratio of the local field potential signal being greater than a second threshold, wherein the power ratio is a ratio of an average power of the first local field potential signal over the first time period to an average power of a second local field potential signal over a second time period prior to application of the electrical stimulation pulse.
7. The implantable closed loop neurostimulation system of claim 1 or 2, wherein the impedance measurement made during a first time period after the application of the electrical stimulation pulse based on the modulated stimulation parameter is made during the first time period after the end of the electrical stimulation pulse is delayed by at least a third time period, and the starting time of the first time period is no earlier than the ending time of the third time period.
8. The implantable closed-loop nerve stimulation system of claim 6, the length of the sliding window being adjusted based on a change in the first rate of change of impedance.
9. A signal processing system comprising an implantable closed loop neurostimulation system of any one of claims 1 to 8.

Description

Implantable closed-loop nerve stimulation system and method for regulating and controlling stimulation parameters thereof Technical Field The application relates to the technical field of nerve regulation and control, in particular to an implantable closed-loop nerve stimulation system and a regulation and control method of stimulation parameters thereof. Background Epilepsy is a neurological disorder that usually requires long-term neuromodulation therapy. The implantable closed-loop nerve stimulation system is widely used because it can respond in real time according to the brain electrical activity of the patient. Existing implantable systems typically detect abnormal neural activity based on electrophysiological signals such as local field potentials (Local Field Potential, LFP) or High-frequency oscillations (High-Frequency Oscillation, HFOs) and trigger a stimulation intervention upon detection of a precursor event. However, since LFP signals are susceptible to interference from myoelectricity, eye movement, device artifacts, etc., the false trigger rate is high in low signal-to-noise environments. Moreover, LFP reflects the outcome of neuronal population discharge and is not an early pathological change of the tissue microenvironment, leading to delayed intervention opportunities. In addition, the existing systems usually adopt fixed stimulation parameters (such as current intensity and electrode combination), and are difficult to adapt to individual differences of patients and dynamic evolution of illness states. Thus, there is a need for an implantable closed-loop neurostimulation system that is capable of adaptive closed-loop neuromodulation based on tissue impedance changes. Disclosure of Invention Aiming at the defects of the existing mode, the application provides an implanted closed-loop nerve stimulation system and a method for regulating and controlling stimulation parameters thereof, and aims to solve the problem that the existing implanted system cannot perform self-adaptive closed-loop nerve regulation and control based on the condition of tissue impedance change. In a first aspect, embodiments of the present application provide an implantable closed-loop nerve stimulation system comprising: A plurality of electrodes implanted intracranially; The dual-frequency impedance measurement circuit is used for applying dual-frequency test current to the plurality of electrodes and collecting response voltage before applying the electric stimulation pulse to the plurality of electrodes to generate a first complex impedance signal, and applying the dual-frequency test current to the plurality of electrodes again and collecting response voltage within a first time period after the end of the electric stimulation pulse to generate a second complex impedance signal; The local field potential recording circuit is used for synchronously collecting first local field potential signals of the areas where the plurality of electrodes are located in the first time period after the electric stimulation pulse is ended; The processing module is used for processing the first complex impedance signal to obtain a first impedance change rate; The spatial gradient calculation module is used for obtaining a three-dimensional spatial impedance gradient based on the spatial coordinates of each electrode and the corresponding impedance value, wherein the spatial coordinates of the plurality of electrodes are prestored in the storage unit; The stimulation parameter regulation and control module is used for regulating and controlling the stimulation parameters of the electric stimulation pulse based on the first impedance change rate and the three-dimensional space impedance gradient; The nerve stimulation driving circuit is used for outputting electric stimulation pulses to the plurality of electrodes according to the regulated stimulation parameters; And the calibration module is used for determining that the second complex impedance signal meets a first condition and/or calibrating the regulated stimulation parameter when the first local field potential signal meets a second condition. In a second aspect, embodiments of the present application provide a method for regulating a stimulation parameter of an implantable closed-loop neural stimulation system, the method being performed by the implantable closed-loop neural stimulation system according to the first aspect, the method comprising: Impedance measurement is carried out by applying double-frequency test currents to the plurality of electrodes, and a first complex impedance signal is obtained; based on the space coordinates and the corresponding impedance values of each electrode in the plurality of electrodes, obtaining a three-dimensional space impedance gradient; regulating and controlling the stimulation parameters of the electric stimulation pulse according to the three-dimensional space impedance gradient and the first impedance change rate determined based o