Transcranial magnetoacoustic stimulation system based on regulation and control of cortical-basal node neural circuit

Abstract

The invention provides a transcranial magnetoacoustic stimulation system based on regulation and control of a cortical-basal node neural circuit. The transcranial magnetoacoustic stimulation system comprises a digital signal generator, a radio frequency power amplifier, an ultrasonic transducer, an oscilloscope, a microelectrode array and two permanent magnets, the digital signal generator is connected with the ultrasonic transducer through the radio frequency power amplifier, and the ultrasonic transducer is provided with a collimator and emits ultrasonic waves in a pulse form; the microelectrode array is arranged on the head of a stimulated object and is used for collecting electroencephalogram signals in real time when stimulation is executed; the permanent magnets are fixed to the two sides of the head of a stimulated object, static magnetic fields and focused ultrasonic stimulation are applied to a target brain area at the same time, and neural activities of the deep brain area are regulated and controlled through the magnetoacoustic coupling effect. According to the application, the magnetoacoustic coupling effect is utilized to perform non-invasive regulation and control on neural activity in the deep brain region, so that the neural oscillation synchronism between the prefrontal lobe and the striatum is enhanced, and the motor and cognitive dysfunction related to the Parkinson's disease is improved.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of transcranial magnetic acoustic stimulation, and particularly relates to a transcranial magnetic acoustic stimulation system based on regulation of a cortical-basal ganglia neural circuit. BACKGROUND

[0002] Parkinson's disease (PD) patients often have complex motor-cognitive comorbidities, which seriously affect the quality of life. Existing clinical intervention methods have significant limitations: (1) Levodopa drug therapy: Although it can alleviate motor symptoms in the short term, long-term use can lead to end-of-dose phenomenon, dyskinesia and other complications, and has limited effect on non-dopamine-mediated cognitive function decline. The fundamental reason is that the mechanism is single, mainly to supplement dopamine, and cannot repair the damaged neural circuit function.

[0003] (2) Deep brain stimulation (DBS): Although it can improve motor symptoms by regulating pathological beta oscillations in the basal ganglia, it is an invasive treatment with risks of intracranial hemorrhage, infection, etc. More importantly, it is difficult to precisely target the regulation of motor and cognitive related circuits such as the cortex-basal ganglia, and may even exacerbate motor and executive function disorders. The fundamental reason is the trauma and spatial resolution limitations of physical electrode implantation, making it difficult to achieve precise regulation of multiple targets and functional specificity.

[0004] (3) Traditional non-invasive neural regulation techniques, such as transcranial magnetic stimulation (TMS) and transcranial electric stimulation (tES): Due to the attenuation and scattering effects of the skull on magnetic fields or electric currents, it is difficult to effectively focus on deep brain regions, the penetration depth is insufficient, and the frequency selective regulation ability is limited. The fundamental reason is that the physical properties of energy forms make it impossible to balance non-invasiveness and deep focusing accuracy. SUMMARY

[0005] Therefore, the application aims to provide a transcranial magnetic acoustic stimulation system based on regulation of a cortical-basal ganglia neural circuit to solve at least one of the above problems.

[0006] To achieve the above-mentioned purpose, the technical solution of the application is as follows: The application provides a transcranial magnetic acoustic stimulation system based on regulation of a cortical-basal ganglia neural circuit, comprising a digital signal generator, a radio frequency power amplifier, an ultrasonic transducer, an oscilloscope, a microelectrode array, and two permanent magnets. The digital signal generator is connected to the ultrasonic transducer through the radio frequency power amplifier, and a collimator is arranged on the ultrasonic transducer. The ultrasonic transducer is aligned with the skull of the stimulation object through the collimator and emits ultrasonic waves in pulse form to target the prefrontal cortex region in the cortex. The digital signal generator is also connected to the oscilloscope. The micro electrode array is arranged on the head of the stimulation subject to collect electroencephalogram signals in real time when the stimulation is performed. The permanent magnet is fixed on both sides of the head of the stimulation subject to form a static magnetic field with a preset intensity, and the deep brain region neural activity is regulated by simultaneously applying the static magnetic field and the focused ultrasound stimulation to the target brain region and utilizing the magnetoacoustic coupling effect.

[0007] Further, the permanent magnet adopts two neodymium-iron-boron permanent magnets with a diameter of 40 mm, a thickness of 10 mm, and a magnetic field strength of 0.3 T, and the magnetic field direction is perpendicular to the surface of the skull.

[0008] Further, the parameters of the focused ultrasound stimulation include that the ultrasonic fundamental wave frequency is 0.5 MHz, the pulse repetition frequency is 1 kHz, the pulse length is 0.5 ms, the ultrasonic pressure is 0.3 MPa, the pulse duration is 400 ms, and the spatial peak pulse average intensity is 2.839 W / cm 2 The total stimulation time is 2 min.

[0009] Further, in the static magnetic field environment, the ultrasonic wave propagates in the direction perpendicular to the magnetic field, and the induced current density formula generated by the magnetoacoustic coupling effect is: ; In the formula, represents the conductivity of the neural tissue, B represents the magnetic induction intensity of the static magnetic field, represents the density of the neural tissue, represents the propagation speed of the ultrasonic wave in the neural tissue, represents the included angle between the static magnetic field and the ultrasound, represents the induced current density.

[0010] Further, an electromagnetic shielding layer is arranged between the ultrasonic transducer and the permanent magnet, and the shielding layer adopts a metal or a permalloy material, and the thickness is .

[0011] Further, the electrode array includes a main electrode and at least four auxiliary electrodes, the main electrode is arranged at the center position of the target brain region, and the at least four auxiliary electrodes are symmetrically distributed around the main electrode, and the distance between the auxiliary electrode and the main electrode is .

[0012] Further, the wire of the electrode array adopts a twisted shielded cable, and the shielding efficiency satisfies , so that the signal-to-noise ratio of the collected signal is not less than 20 .

[0013] Compared with existing technologies, the transcranial magnetic acoustic stimulation system based on the modulation of the cortical-basal ganglia neural circuit described in this application has the following beneficial effects: The transcranial magnetoacoustic stimulation system described in this application, which modulates the neural activity in deep brain regions by simultaneously applying a static magnetic field and focused ultrasound stimulation to the cranial region, utilizes the magnetoacoustic coupling effect to regulate neural activity in these regions, thereby enhancing the synchronicity of neural oscillations between the prefrontal cortex and striatum and improving motor and cognitive dysfunctions associated with Parkinson's disease. Attached Figure Description

[0014] The accompanying drawings, which form part of this application, are used to provide a further understanding of this application. The illustrative embodiments and descriptions of this application are used to explain this application and do not constitute an undue limitation of this application. In the drawings: Figure 1 This is a schematic diagram of a transcranial magnetoacoustic stimulation system based on the modulation of the cortex-basal ganglia neural circuit as described in an embodiment of this application; Figure 2 This is a schematic diagram of the stimulation test pulse sequence parameters described in the embodiments of this application; Figure 3 This is a schematic diagram illustrating the principle of transcranial magnetoacoustic stimulation as described in the embodiments of this application.

[0015] Explanation of reference numerals in the attached figures: Detailed Implementation

[0016] To make the objectives, technical solutions, and advantages of this application clearer, the following detailed description is provided in conjunction with specific embodiments and the accompanying drawings.

[0017] It should be noted that, unless otherwise defined, the technical or scientific terms used in the embodiments of this application should have the ordinary meaning understood by one of ordinary skill in the art to which this application pertains. The terms "first," "second," and similar terms used in the embodiments of this application do not indicate any order, quantity, or importance, but are merely used to distinguish different components. Terms such as "comprising" or "including" mean that the element or object preceding the word encompasses the elements or objects listed after the word and their equivalents, without excluding other elements or objects. Terms such as "connected" or "linked" are not limited to physical or mechanical connections, but can include electrical connections, whether direct or indirect. Terms such as "upper," "lower," "left," and "right" are only used to indicate relative positional relationships; when the absolute position of the described object changes, the relative positional relationship may also change accordingly.

[0018] Please see Figure 1As shown, this embodiment provides a transcranial magnetoacoustic stimulation system based on the modulation of the corticobasal ganglia neural circuit, including a digital signal generator, a radio frequency power amplifier, an ultrasonic transducer, an oscilloscope, a microelectrode array, and two permanent magnets; The digital signal generator is connected to the ultrasonic transducer via a radio frequency power amplifier. The ultrasonic transducer is equipped with a collimator. The ultrasonic transducer is aligned with the skull of the subject through the collimator and emits ultrasonic waves in the form of pulses to target the prefrontal cortex region in the cortex. The digital signal generator is also connected to an oscilloscope. The microelectrode array is placed on the head of the subject being stimulated to collect electroencephalogram (EEG) signals in real time during stimulation. Permanent magnets are fixed on both sides of the head of the subject to be stimulated to form a static magnetic field with a preset intensity. By simultaneously applying the static magnetic field and focused ultrasound stimulation to the target brain region, the magnetic-acoustic coupling effect is used to regulate the neural activity of deep brain regions.

[0019] Specifically, in this embodiment, the cortical region is selected as the prefrontal cortex, and the striatum is selected as the basal ganglia region. By simultaneously applying static magnetic field and focused ultrasound stimulation to the cranial region, the magnetic acoustic coupling effect is used to non-invasively regulate the neural activity of the deep brain regions, thereby enhancing the neural oscillation synchronization between the prefrontal cortex and the striatum and improving Parkinson's disease-related motor and cognitive dysfunction.

[0020] Furthermore, a static magnetic field of preset intensity is formed on the head of the stimulated individual, and focused ultrasound signals are precisely applied to the prefrontal cortex region. The magnetic field and ultrasound act simultaneously within the target brain region, regulating the neuronal membrane potential and the activity of mechanosensitive ion channels through magnetoacoustic coupling. This enhances the power and synchronicity of the theta-band neural oscillations in the prefrontal-striatal neural circuit. By enhancing the power and synchronicity of the theta-band neural oscillations in the prefrontal-striatal neural circuit, abnormally damaged neural oscillation rhythms are restored. This improves the pathological state of Parkinson's disease from the functional level of the neural circuit, which is different from traditional treatments that only target neurotransmitter levels or a single brain region.

[0021] Transcranial magnetoacoustic stimulation (TMS) is a non-invasive neuromodulation technique based on multi-physical field coupling. It boasts advantages such as non-invasiveness, strong deep penetration, and high spatiotemporal resolution. Its working principle is as follows: Figure 3 As shown, in a static magnetic field environment, ultrasound waves perpendicular to the magnetic field direction are applied, causing charged ions to vibrate along the propagation direction under the influence of the ultrasound waves. In the magnetic field, these charged ions are deflected by the Lorentz force, forming an induced current, which in turn affects the firing activity of neuronal groups, achieving non-invasive regulation of nerve function.

[0022] The system consists of the following components: Figure 1As shown, the device mainly consists of two arbitrary signal generators, a radio frequency power amplifier, an ultrasonic transducer, an oscilloscope, and two cylindrical neodymium iron boron permanent magnets. To provide a stable static magnetic field environment, two neodymium iron boron permanent magnets with a diameter of 40 mm, a thickness of 10 mm, and a magnetic field strength of 0.3 T were used in the experiment. The ultrasonic signal was generated by the two signal generators, amplified by the radio frequency power amplifier, and then transmitted to the ultrasonic transducer to ensure effective acoustic-magnetic coupling stimulation.

[0023] The ultrasonic stimulation parameters were set as follows: fundamental frequency of ultrasound was 0.5 MHz, pulse repetition frequency was 1 kHz, pulse length was 0.5 ms, pulse duration was 400 ms, ultrasonic pressure reached 0.3 MPa, and the average intensity of the spatial peak pulse was 2.839 W / cm². 2 The total stimulation duration is 2 minutes. For details on the pulse sequence parameter relationships, please refer to [link / reference needed]. Figure 2 During the experiment, an ultrasound gel was used as the coupling medium to ensure effective energy transfer between the ultrasound probe and the mouse scalp. During stimulation, the mice were anesthetized with 1% isoflurane, and the ultrasound transducer was precisely aligned with the skull, targeting the prefrontal cortex region.

[0024] By combining a static magnetic field of 0.3 T with focused ultrasound of 0.5 MHz using specific parameters in a pulsed manner, a novel magnetoacoustic coupling energy paradigm for non-invasive deep brain nerve modulation is formed. This combination is not a simple superposition; the static magnetic field is used to modulate the neuronal excitation threshold, while focused ultrasound modulates firing synchronization by acting mechanically on mechanosensitive ion channels on the cell membrane. The two work synergistically to overcome the limitations of single energy forms in terms of penetration depth and cell-specific modulation.

[0025] Within the range of stimulation parameters set in this embodiment, the stimulation process will not cause significant damage to the brain tissue structure, is unlikely to cause abnormal nerve discharges or irreversible tissue changes, has good biocompatibility and tissue compatibility, and is suitable for repeated stimulation over a long period of time.

[0026] In a static magnetic field environment, ultrasound propagates in a direction perpendicular to the magnetic field, causing the vibration of charged ions in nerve tissue, and the ion movement speed ( ) and ultrasonic pressure ( The following relationship exists between them: ; In the formula, Indicates the density of nerve tissue. This represents the speed at which ultrasound waves travel through nerve tissue.

[0027] Under the influence of a magnetic field, positively and negatively charged ions experience the Lorentz force, calculated as follows: ; In the formula, Represents the Lorentz force. This indicates the electric charge carried by the ions. It represents the magnetic induction intensity of a static magnetic field.

[0028] Under the influence of the Lorentz force, vibrating ions are deflected, forming a directional induced current. According to Montalibet theory, the induced current density J is expressed as: ; In the formula, Indicates the electrical conductivity of nerve tissue. This indicates the angle between the static magnetic field and the ultrasound. This refers to the induced current density generated by the magnetoacoustic coupling effect, expressed in μA / cm². 2 .

[0029] Combining the Lorentz force equation, it can be further expressed as: ; Furthermore, in brain tissue, ultrasound intensity The relationship with ultrasonic pressure is as follows: ; Finally, combining the above formulas, the induced current density J can be further expressed as: .

[0030] Furthermore, by repeatedly performing the above-mentioned magnetoacoustic stimulation process, the abnormal and damaged neural circuit rhythms can be continuously regulated, thereby improving the motor and cognitive dysfunctions of Parkinson's disease at the neural circuit level.

[0031] In some embodiments, an electromagnetic shielding layer is provided between the ultrasonic transducer and the permanent magnet, and the shielding layer adopts... - Metal or permalloy material, thickness of This is to limit the transient electromagnetic interference generated by the magnetoacoustic stimulation device to outside the detection frequency band (0.5Hz-100Hz) of the electrode array.

[0032] In some embodiments, the electrode array includes a main electrode and at least four auxiliary electrodes. The main electrode is positioned at the center of the target brain region, and the at least four auxiliary electrodes are symmetrically distributed around the main electrode. The distance between the auxiliary electrodes and the main electrode is [missing information]. ; The electrode array uses twisted-pair shielded cables as its conductors, and its shielding efficiency meets the requirements. To improve the signal-to-noise ratio of the acquired signal No less than 20 .

[0033] Specifically, in this embodiment, the main electrode and the auxiliary electrode together constitute a local spatial filtering network, and the comprehensive neural activity characteristics of the target brain region are calculated using a weighted average algorithm, with weight coefficients... Distance between each electrode and the projection point of the target brain region cortex (Unit: cm) shows an inverse relationship, that is , It is a constant.

[0034] In practical implementation, the weights should be jointly verified with spatial filtering based on the conductor model or Laplace / lead-field inversion to quantify the bias caused by the inverse distance approximation.

[0035] This embodiment uses a static magnetic field and focused ultrasound to work synchronously, so that the magnetic field and sound field produce a synergistic regulatory effect in the target brain region. The stimulation parameters can be precisely set and repeatedly controlled, which is conducive to achieving stable and repeatable neuromodulation effects, and facilitates clinical promotion and equipment standardization.

[0036] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention, and they should all be covered within the scope of the claims and specification of the present invention.

[0037] The embodiments of this application are intended to cover all such substitutions, modifications, and variations that fall within the broad scope of the appended claims. Therefore, any omissions, modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the embodiments of this application should be included within the protection scope of this application.

Claims

1. A transcranial magnetoacoustic stimulation system based on the modulation of the cortex-basal ganglia neural circuit, characterized in that: It includes a digital signal generator, an RF power amplifier, an ultrasonic transducer, an oscilloscope, a microelectrode array, and two permanent magnets; The digital signal generator is connected to the ultrasonic transducer via a radio frequency power amplifier. The ultrasonic transducer is equipped with a collimator. The ultrasonic transducer is aligned with the skull of the subject being stimulated via the collimator and emits ultrasonic waves in pulse form to target the prefrontal cortex region in the cortex. The digital signal generator is also connected to the oscilloscope. The microelectrode array is placed on the head of the subject being stimulated to collect electroencephalogram (EEG) signals in real time during stimulation. The permanent magnets are fixed on both sides of the head of the subject to be stimulated to form a static magnetic field with a preset intensity. By simultaneously applying the static magnetic field and focused ultrasound stimulation to the target brain region, the magnetic-acoustic coupling effect is used to regulate the neural activity of the deep brain region.

2. The transcranial magnetoacoustic stimulation system based on the modulation of the cortical-basal ganglia neural circuit according to claim 1, characterized in that: The permanent magnets are two neodymium iron boron permanent magnets with a diameter of 40 mm, a thickness of 10 mm, and a magnetic field strength of 0.3 T, with the magnetic field direction perpendicular to the skull surface.

3. The transcranial magnetoacoustic stimulation system based on the modulation of the cortical-basal ganglia neural circuit according to claim 1, characterized in that: The parameters for the focused ultrasound stimulation include: a fundamental ultrasound frequency of 0.5 MHz, a pulse repetition frequency of 1 kHz, a single pulse width of 0.5 ms, an ultrasound pressure of 0.3 MPa, a pulse duration of 400 ms, and a spatial peak pulse average intensity of 2.839 W / cm². 2 The total stimulation duration is 2 minutes.

4. The transcranial magnetoacoustic stimulation system based on the modulation of the cortical-basal ganglia neural circuit according to claim 1, characterized in that: In a static magnetic field environment, ultrasonic waves propagate along a direction perpendicular to the magnetic field. The formula for the induced current density generated by the magnetoacoustic coupling effect is: ； In the formula, B represents the electrical conductivity of nerve tissue, and B represents the magnetic flux density of the static magnetic field. Indicates the density of nerve tissue. This represents the speed at which ultrasound waves travel through nerve tissue. This indicates the angle between the static magnetic field and the ultrasound. This represents the induced current density.

5. A transcranial magnetic acoustic stimulation system based on the modulation of the cortical-basal ganglia neural circuit according to claim 1, characterized in that: An electromagnetic shielding layer is provided between the ultrasonic transducer and the permanent magnet, and the shielding layer adopts... - Metal or permalloy material, thickness of .

6. The transcranial magnetoacoustic stimulation system based on the modulation of the cortical-basal ganglia neural circuit according to claim 1, characterized in that: The electrode array includes a main electrode and at least four auxiliary electrodes. The main electrode is positioned at the center of the target brain region, and the at least four auxiliary electrodes are symmetrically distributed around the main electrode. The distance between the auxiliary electrodes and the main electrode is [missing information]. .

7. A transcranial magnetoacoustic stimulation system based on the modulation of the cortical-basal ganglia neural circuit according to claim 6, characterized in that: The conductors of the electrode array are made of twisted-pair shielded cable, and their shielding efficiency meets the requirements. To improve the signal-to-noise ratio of the acquired signal No less than 20 .

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