Time-interleaved electrical stimulation system based on transnasal sphenoid electrodes

Abstract

The application discloses a time interference electric stimulation system based on a transsphenoidal electrode, which comprises an image acquisition and analysis unit, a brain model is established by collecting and fusing MRI images and CT images of a subject, and a first electrode position, a second electrode position and stimulation parameters required for generating a stimulation waveform in a stimulation area are determined based on simulation of the brain model; a stimulation unit comprises a transsphenoidal electrode, a scalp electrode and a stimulation waveform generator, and is used for generating a stimulation waveform in the stimulation area, and the stimulation area is a midbrain reticular formation area; and an implantation unit guides implantation of the transsphenoidal electrode into the first electrode position based on the brain model. The system also combines electroencephalogram signals and clinical evaluation data to jointly observe stimulation effects, effectively solves the short board that existing wake-up technologies have poor targeting and high trauma, realizes minimally invasive and precise wake-up intervention of the midbrain reticular formation, and improves the wake-up efficiency and safety of the consciousness disorder population, and the system has a simple structure and is easy to popularize clinically.

Description

Technical Field

[0001] This application belongs to the field of neuromodulation technology, specifically relating to a time-interference electrical stimulation system based on transnasal sphenoid sinus electrodes. Background Technology

[0002] Disorders of consciousness (DOC) refer to clinical syndromes caused by various factors that impair the function of the central nervous system, leading to a decline in the level of consciousness or alterations in the content of consciousness. These include coma, vegetative state, and minimally conscious state. The core goals of clinical treatment are arousal intervention and restoration of neurological function. The midbrain reticular formation is a key nucleus for maintaining the brain's arousal state. As an important pathway for consciousness transmission, the activation of its neural activity is the core mechanism for achieving consciousness arousal, thus making it an important target brain region for arousal therapy in patients with disorders of consciousness.

[0003] Currently, neuromodulation techniques for promoting arousal targeting the midbrain reticular formation mainly fall into two categories: invasive deep brain stimulation (DBS) and non-invasive scalp electrical stimulation. Invasive DBS requires craniotomy to implant electrodes into the target area of ​​the brain. Although it can achieve targeted stimulation, the surgery is highly invasive, carries a high risk of postoperative complications, and is expensive, making it difficult to widely promote in clinical practice. Non-invasive scalp electrical stimulation, while having the advantage of being minimally invasive, suffers from significant attenuation of the electric field in the deep brain due to the obstruction of the skull, making it difficult to accurately target the midbrain reticular formation. This results in poor targeting and low arousal efficiency, failing to meet the needs of precise clinical treatment.

[0004] There is a need for an electrical stimulation system that combines high safety with deep brain targeting to provide an efficient and safe arousal treatment. Summary of the Invention

[0005] To address the problems existing in the prior art, the purpose of this application is to provide a time-interference electrical stimulation system based on transnasal sphenoid electrodes. By generating time-interference electrical stimulation waveforms through the synergistic effect of transnasal sphenoid electrodes and scalp electrodes, a minimally invasive and precise targeted stimulation of the midbrain reticular formation can be achieved. Combined with acquired MRI and CT images, modeling simulation and neuronavigation can be implemented to determine the optimal stimulation parameters and electrode positions, thereby improving the accuracy of stimulation and effectively solving the shortcomings of poor targeting and high invasiveness of existing arousal techniques.

[0006] Specifically, this application relates to a time-interference electrical stimulation system based on transsphenoidal electrodes, comprising: an image acquisition and analysis unit for acquiring and fusing MRI and CT images of a subject to establish a brain model, and for determining the first electrode position, second electrode position, and stimulation parameters required to generate a stimulation waveform in a stimulation region based on brain model simulation; a stimulation unit including a transsphenoidal electrode, a scalp electrode, and a stimulation waveform generator for generating a stimulation waveform in a stimulation region, wherein the stimulation region is the midbrain reticular formation region; and an implantation unit for guiding the implantation of the transsphenoidal electrode at the first electrode position based on the brain model.

[0007] According to some embodiments of this application, determining the first electrode position, second electrode position, and stimulation parameters required to generate a stimulation waveform in the stimulation region based on brain model simulation includes: the image acquisition and analysis unit simulates in the brain model the optional stimulation waveform generated in the stimulation region when the transsphenoidal electrode and the scalp electrode have different optional electrode positions and optional stimulation parameters; in response to the optional stimulation waveform with the highest electric field strength and / or the highest electric field focusing degree, the image acquisition and analysis unit sets the optional electrode position corresponding to the optional stimulation waveform as the first electrode position and the second electrode position, and sets the optional stimulation parameter as the stimulation parameter.

[0008] According to some embodiments of this application, the implantation of a transsphenoidal electrode into the first electrode position based on a brain model includes: the implantation unit aligning the coordinates of the brain model with the real physical coordinates through registration and alignment, so as to determine the position of the first electrode by means of the tip of the navigation needle; the implantation unit continuously monitoring the navigation coordinates of the transsphenoidal electrode in the brain model through a sensor to determine the real physical coordinates of the transsphenoidal electrode; and the implantation unit guiding the transsphenoidal electrode to the first electrode position and fixing the transsphenoidal electrode based on the position of the first electrode and the real physical coordinates.

[0009] According to some embodiments of this application, the implantation unit continuously monitors the navigation coordinates of the transsphenoidal electrode in the brain model using sensors, including: the implantation unit continuously collects optical or electromagnetic information emitted by the transsphenoidal electrode using sensors to continuously determine the navigation coordinates of the transsphenoidal electrode in the brain model.

[0010] According to some embodiments of this application, generating a stimulation waveform in the stimulation area includes: a stimulation waveform generator providing a first frequency fundamental electric field and a second frequency fundamental electric field to a transsphenoidal electrode and a scalp electrode respectively based on stimulation parameters; the transsphenoidal electrode and the scalp electrode outputting the first frequency fundamental electric field and the second frequency fundamental electric field at the first electrode position and the second electrode position respectively, so as to generate a stimulation waveform in the stimulation area.

[0011] According to some embodiments of this application, a transsphenoidal electrode is fixed at the first electrode position via the transsphenoidal sinus, and a scalp electrode is fixed at the second electrode position on the scalp surface; the frequency difference between the first frequency fundamental electric field and the second frequency fundamental electric field is set to 80 Hz ~ 200 Hz, and the amplitude of the stimulation waveform is set to 0 ~ 5 mA.

[0012] According to some embodiments of this application, the time-interference electrical stimulation system based on transnasal sphenoid electrodes further includes an evaluation unit; the evaluation unit acquires the subject's electroencephalogram (EEG) signals and / or clinical evaluation data to analyze the electrical stimulation effect of the stimulation waveform on the stimulation area.

[0013] According to some embodiments of this application, the assessment unit includes an EEG signal acquisition subunit, a behavioral assessment subunit, and an analysis subunit; the EEG signal acquisition subunit acquires and processes EEG signals to obtain EEG characteristic parameters; the behavioral assessment subunit acquires and processes clinical assessment data to obtain behavioral assessment data; and the analysis subunit processes the EEG characteristic parameters and behavioral assessment data to obtain the electrical stimulation effect.

[0014] According to some embodiments of this application, the time-interference electrical stimulation system based on transnasal sphenoid electrodes further includes a control unit; the control unit controls the image acquisition and analysis unit to adjust the stimulation parameters based on the electrical stimulation effect, so that the stimulation unit adjusts the stimulation waveform generated by the stimulation region.

[0015] According to some embodiments of this application, the stimulation unit further includes a clock timing control subunit; the clock timing control subunit adjusts the time axis of the stimulation waveform generated by the stimulation unit in the stimulation region to control the stimulation interval and stimulation time of the stimulation waveform generated by the stimulation unit in the stimulation region.

[0016] The beneficial effects of the time-interference electrical stimulation system based on transnasal sphenoid sinus electrodes described in this application are as follows.

[0017] The system uses transsphenoidal electrodes and scalp electrodes to generate time-interference electrical stimulation waveforms. The transsphenoidal approach shortens the distance between the electrodes and the midbrain reticular formation, reducing the attenuation of the electric field by the skull. Combined with the deep targeting capability of time-interference technology, it achieves minimally invasive and precise targeted stimulation of the midbrain reticular formation. Compared with simple scalp electrical stimulation, the targeting capability is significantly improved. Compared with invasive DBS, the trauma is greatly reduced, improving the safety and effectiveness of the treatment.

[0018] The system combines CT and MRI image modeling with in vitro simulation technology to simulate the electric field distribution under different electrode positions and stimulation parameters, determine the optimal stimulation scheme, and complete electrode implantation under neuronavigation guidance, further improving the accuracy of stimulation and avoiding the problem of poor efficacy caused by blind stimulation.

[0019] The system employs a multimodal assessment approach combining EEG signals and clinical evaluation data to verify the stimulation effect from both objective EEG characteristics and subjective behavioral manifestations. This results in a more comprehensive and accurate assessment. Furthermore, the system dynamically adjusts stimulation parameters based on the assessment results, enabling personalized awakening treatment for DOC subjects and effectively improving awakening efficiency.

[0020] The system has a simple structure, a clear workflow for the coordinated operation of each unit, minimally invasive and convenient electrode implantation, flexible adjustment of stimulation parameters, and is easy to promote and apply in clinical practice, providing a new and effective means for the awakening treatment of people with impaired consciousness. Attached Figure Description

[0021] Figure 1 The figure shows a schematic diagram of a time-interference electrical stimulation system based on transnasal sphenoid electrodes according to an embodiment of this application.

[0022] Figure 2 The illustration shows a schematic diagram of the use of a time-interference electrical stimulation system based on transnasal sphenoid electrodes according to an embodiment of this application.

[0023] Figure 3 The figure shows a simulation result of a brain model of a time-interference electrical stimulation system based on transnasal sphenoid electrodes according to an embodiment of this application.

[0024] Figure 4 The figure shows the simulation results of the electrical stimulation system based on the transnasal sphenoid electrode according to an embodiment of this application. Detailed Implementation

[0025] The present application is further illustrated below with reference to embodiments. It should be understood that the embodiments are only used to further illustrate and explain the present application and are not intended to limit the present application.

[0026] Unless otherwise defined, technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art. While similar or identical methods and materials may be applied in experimental or practical applications, materials and methods are described herein. In case of conflict, the definitions included herein shall prevail. Furthermore, materials, methods, and examples are for illustrative purposes only and are not intended to be limiting. The present application is further described below with reference to specific embodiments, but is not intended to limit the scope of the application.

[0027] Application Overview As mentioned above, current invasive electrical stimulation protocols are high-risk, expensive, and cannot guarantee high stimulation targeting. These factors limit the clinical application of DOC (Digital Oral Consciousness) arousal techniques based on invasive electrical stimulation.

[0028] The transsphenoid sinus approach is a classic minimally invasive approach in neurosurgery. Electrode placement via this approach effectively shortens the distance to the midbrain reticular formation, reduces the attenuation of the electric field by the skull, and improves the targeting accuracy of the electric field. This application proposes a time-interference electrical stimulation system based on transsphenoid sinus electrodes, combined with a time-interference electrical stimulation system using transsphenoid sinus and scalp electrodes. Through preoperative image modeling and simulation to determine the stimulation protocol, and neuronavigation-guided electrode implantation, it achieves minimally invasive and precise targeted stimulation of the midbrain reticular formation. Furthermore, multimodal assessment methods are used to verify the stimulation effect, providing an efficient and safer arousal treatment option for individuals with impaired consciousness.

[0029] After introducing the basic principles and advantages of this application, various non-limiting embodiments of this application will be described in detail below with reference to the accompanying drawings.

[0030] Exemplary System Figure 1 The figure shows a schematic diagram of a time-interference electrical stimulation system based on transnasal sphenoid electrodes according to an embodiment of this application.

[0031] refer to Figure 1 The time-interference electrical stimulation system based on transnasal sphenoid sinus electrodes according to embodiments of this application includes the following components.

[0032] The image acquisition and analysis unit collects and fuses MRI and CT images of the subject to establish a brain model, and determines the first electrode position, second electrode position, and stimulation parameters required to generate stimulation waveforms in the stimulation area based on brain model simulation.

[0033] The stimulation unit includes a transnasal sphenoid sinus electrode, a scalp electrode, and a stimulation waveform generator, used to generate a stimulation waveform in the stimulation area, which is the midbrain reticular formation region. Figure 2 The illustration shows the process by which the transsphenoidal electrode of the stimulation unit, via the transsphenoidal approach, and the scalp electrode located on the scalp surface generate low-frequency interference waveforms in a specific stimulation area, namely the midbrain reticular formation region.

[0034] And, the implantation unit, which guides the implantation of the transnasal sphenoidal electrode at the first electrode location based on the brain model.

[0035] In this application, the image acquisition and analysis unit determines the first electrode position, second electrode position, and stimulation parameters required to generate a stimulation waveform in the stimulation region based on brain model simulation. This includes: the image acquisition and analysis unit simulating in the brain model the optional stimulation waveform generated in the stimulation region when the transsphenoidal electrode and scalp electrode have different optional electrode positions and optional stimulation parameters; in response to the optional stimulation waveform with the highest electric field strength and / or the highest electric field focusing, the image acquisition and analysis unit sets the optional electrode position corresponding to the optional stimulation waveform as the first electrode position and the second electrode position, and sets the optional stimulation parameter as the stimulation parameter.

[0036] In one example, the time-interference electrical stimulation waveform generated by the transsphenoidal electrode and scalp electrode meets the response conditions set by the parameters for precise targeting of the midbrain reticular formation through preoperative image modeling and simulation. These conditions are: the image acquisition and analysis unit determines that the electric field strength of the interference electric field formed by the time-interference electrical stimulation waveform in the midbrain reticular formation reaches a preset field strength threshold and the coverage of the midbrain reticular formation is not less than 80%; and the stimulation amplitude of the time-interference electrical stimulation waveform on surrounding non-target brain regions, such as the thalamus and cerebral cortex, is lower than a preset safety stimulation threshold or interference stimulation threshold. The positions of the transsphenoidal electrode and the scalp electrode are determined as the first electrode position and the second electrode position, respectively, and the stimulation parameters are recorded. The image acquisition and analysis unit, a computer processor and storage medium, sets selectable electrode positions, selectable stimulation parameters, and a brain model by running 3D reconstruction and simulation software. It also runs parameter optimization algorithms, such as grid search, genetic algorithms, and Bayesian algorithms, to simulate on the brain model to determine the first electrode position, the second electrode position, and the stimulation parameters.

[0037] In this application, guiding the implantation of the transsphenoidal electrode at the first electrode position based on the brain model includes: the implantation unit aligning the coordinates of the brain model with the actual physical coordinates through registration and alignment, so as to determine the position of the first electrode by means of the tip of the navigation needle; the implantation unit continuously monitoring the navigation coordinates of the transsphenoidal electrode in the brain model through a sensor to determine the actual physical coordinates of the transsphenoidal electrode; the implantation unit guiding the transsphenoidal electrode to the first electrode position and fixing the transsphenoidal electrode based on the first electrode position and the actual physical coordinates.

[0038] In this application, the implantation unit continuously monitors the navigation coordinates of the transsphenoidal electrode in the brain model using sensors, including: the implantation unit continuously collects optical or electromagnetic information emitted by the transsphenoidal electrode using sensors to continuously determine the navigation coordinates of the transsphenoidal electrode in the brain model.

[0039] In one example, a 3.0 T MRI scanner and a 64-slice spiral CT scanner were used to acquire preoperative high-resolution MRI and CT images of the subject. The image acquisition and analysis unit acquired these images and used medical imaging 3D reconstruction software, such as Mimics, to construct a 3D brain model of the subject's head anatomy. Figure 3 As shown, the model clearly recreates the anatomical structures of the midbrain reticular formation, sphenoid sinus, and skull. Different placements of transsphenoidal and scalp electrodes are simulated in the brain model, such as the implantation depth of the transsphenoidal electrodes and the scalp sites for the scalp electrodes, to simulate the electric field distribution characteristics of the time-interference point stimulation waveforms generated by the transsphenoidal and scalp electrodes under different stimulation parameters. Through electric field simulation analysis, the positions of each electrode and the initial values ​​of stimulation parameters when the electric field reaches its peak in the midbrain reticular formation region are determined, such as the optimal stimulation amplitude of 2 mA, stimulation frequency of 100 Hz, and stimulation time of 20 min. The implantation unit imports the brain model data into a neuronavigation system, such as the Stereotactic Navigation system. Under real-time guidance of neuronavigation, the transsphenoidal electrodes are precisely implanted in preset positions using a minimally invasive transsphenoidal approach. Simultaneously, the optimal positions of the scalp electrodes are set, for example, placing the scalp electrodes at the OZ and PZ sites in the occipital region based on the international 10-20 EEG electrode positioning system.

[0040] In this application, generating a stimulation waveform in the stimulation region includes: the stimulation waveform generator providing a first-frequency fundamental electric field and a second-frequency fundamental electric field to the transsphenoidal electrode and scalp electrode, respectively, based on the stimulation parameters; the transsphenoidal electrode and scalp electrode outputting the first-frequency fundamental electric field and the second-frequency fundamental electric field at the first electrode position and the second electrode position, respectively, to generate the stimulation waveform in the stimulation region. The stimulation waveform generator includes at least a waveform generator and a current source to output current, thereby enabling the electrodes to output the fundamental electric field. Optionally, the stimulation waveform generator may further include amplitude modulation, frequency conversion, and filtering circuits to improve the stability and accuracy of the output current.

[0041] In this application, the transsphenoidal electrode is fixed at the first electrode position via the transsphenoidal sinus, and the scalp electrode is fixed at the second electrode position on the scalp surface; the frequency difference between the first frequency fundamental electric field and the second frequency fundamental electric field is set to 80 Hz ~ 200 Hz, and the amplitude of the stimulation waveform is set to 0 ~ 5 mA.

[0042] In one example, the stimulation unit includes a pair of transsphenoidal electrodes, a pair of scalp electrodes, a stimulation waveform generator electrically connected to the two pairs of electrodes, and a clock timing control subunit. The transsphenoidal electrodes can be platinum-iridium alloy electrodes, and the scalp electrodes can be silver / silver chloride electrodes. The transsphenoidal electrodes are positioned via a transsphenoidal approach, and the scalp electrodes are positioned at the scalp target points corresponding to the midbrain reticular formation. The stimulation waveform generator outputs a 2000 Hz high-frequency fundamental electric field (which can be understood as an electric field formed by current) to the transsphenoidal electrodes and a 2100 Hz high-frequency fundamental electric field (which can be understood as an electric field formed by current) to the scalp electrodes. The two fundamental electric fields intersect in the midbrain reticular formation region, thereby generating a 100 Hz low-frequency envelope modulation amplitude waveform, i.e., a time-interference electrical stimulation coherent waveform, as the stimulation waveform to achieve deep targeted stimulation of the midbrain reticular formation. The stimulation parameters of the stimulation unit are adjustable, and the preferred range is: stimulation intensity 0 ~ 5 mA, stimulation time 15 min ~ 30 min, and stimulation frequency 80 Hz ~ 200 Hz, so as to achieve the optimal intervention effect on DOC.

[0043] In a specific example, based on T1 and T2 imaging data from healthy subjects' MRI, an image acquisition and analysis unit is used to accurately reconstruct a three-dimensional anatomical model of the subject's head and neck as a brain model. This ensures that the brain model can realistically replicate the characteristics of the anatomical structures of the head and neck involved in the stimulation, providing a reliable anatomical basis for subsequent electrical stimulation simulations. The brain model is imported into the Simnibs stimulation simulation platform, and occipital lobe bone electrical stimulation, transnasal sphenoid sinus electrical stimulation, and transnasal time-interference electrical stimulation based on the transnasal sphenoid sinus electrode time-interference electrical stimulation system according to the embodiments of this application are performed. Specifically, the transnasal sphenoid sinus electrode used for transnasal sphenoid sinus electrical stimulation and the transnasal sphenoid sinus electrode used for transnasal time-interference electrical stimulation provide stimulation waveforms to the target brain region at the same first electrode position. Specifically, targeted electrical stimulation simulation experiments are conducted on the target brain region, namely the brainstem reticular formation, to verify the targeted modulation effect of different electrical stimulation methods on the target brain region and the control level of interference to non-target brain regions.

[0044] like Figure 4As shown in the simulation results, transnasal time-interference electrical stimulation effectively enhances the electric field coverage of the target brain region and achieves high electric field focusing, enabling precise targeted stimulation of the target brain region. In contrast, transnasal sphenoid sinus electrical stimulation alone has limited coverage of the target brain region and fails to encompass the entire brainstem reticular formation. Traditional occipital bone electrical stimulation generates a stimulating electric field in the target brain region, but its focusing is insufficient, resulting in a relatively loose overall stimulation. Furthermore, transnasal time-interference electrical stimulation minimizes electric field interference to other non-target brain regions, significantly improving the targeting specificity of the electrical stimulation and avoiding unnecessary stimulation of neurons in non-target brain regions. This addresses the technical pain points of traditional electrical stimulation, such as poor targeting and easy interference with surrounding brain regions. Traditional occipital bone electrical stimulation interferes with a large volume of non-target brain regions, making it clearly unsuitable for practical arousal therapy.

[0045] Based on this, further simulation results show that when the intensity of the stimulation waveform applied by transnasal time-interference electrical stimulation is 5 mA, the electric field distribution generated in the target brain region is... E The electric field strength remained stable within a reasonable range of 0.1-0.25. Combined with neurophysiological mechanisms, this range effectively induced arousal effects in neurons in the target region, thus meeting the practical application requirements of transnasal time-interference electrical stimulation for neuronal arousal regulation. This example provides reliable data support for the effective clinical application of the aforementioned transnasal sphenoid sinus electrode-based time-interference electrical stimulation system.

[0046] In this application, the stimulation unit further includes a clock timing control subunit; the clock timing control subunit adjusts the time axis of the stimulation unit generating stimulation waveforms in the stimulation region to control the stimulation interval and stimulation time of the stimulation unit generating stimulation waveforms in the stimulation region. In one example, the clock timing control unit is connected to the stimulation waveform generator to adjust the time axis of the stimulation program, ensuring that the electrode stimulation interval and the stimulation time of the unadjusted parameters remain unchanged.

[0047] In this application, the time-interference electrical stimulation system based on transnasal sphenoid electrodes further includes an evaluation unit; the evaluation unit acquires the subject's electroencephalogram (EEG) signals and / or clinical assessment data to analyze the electrical stimulation effect of the stimulation waveform on the stimulation region. Specifically, the evaluation unit includes an EEG signal acquisition subunit, a behavioral assessment subunit, and an analysis subunit; the EEG signal acquisition subunit acquires and processes EEG signals to obtain EEG characteristic parameters; the behavioral assessment subunit acquires and processes clinical assessment data to obtain behavioral assessment data; and the analysis subunit processes the EEG characteristic parameters and behavioral assessment data to obtain the electrical stimulation effect.

[0048] The EEG signal acquisition subunit, behavior assessment subunit, and analysis subunit are three relatively independent logical operation units divided by the computer processor according to their functions. When the processor executes different computer program instruction sets stored in the storage medium, it can respectively realize the functions of the EEG signal acquisition subunit, behavior assessment subunit, and analysis subunit. In one example, the EEG signal acquisition subunit also includes a 32-channel EEG recorder, which acquires the subject's EEG signals before, during, and after stimulation at a sampling frequency of 500 Hz. These signals are then sent to the computer processor for preprocessing and feature extraction, including filtering, artifact removal, and noise reduction, to obtain objective EEG characteristic parameters such as the rhythm, amplitude, and brain region coherence of delta waves, theta waves, and alpha waves. The behavioral assessment subunit also includes human-computer interaction devices, such as touchscreens or computer input / output peripherals, which provide subjects with the Glasgow Coma Scale (GCS) and the Coma Recovery Scale-Revised (CRS-R) and receive subjects' scores on the scales to assess their state of consciousness. This assessment evaluates behavioral status across six dimensions: auditory, visual, motor, verbal, communicative, and arousal, sending the scores as behavioral assessment data to the computer processor. The analysis subunit determines the assessment results of the electrical stimulation effect based on EEG characteristic parameters and the behavioral assessment data. For example, if the analysis subunit detects an increase in the proportion of alpha waves and a decrease in the proportion of delta waves in the EEG characteristic parameters, it indicates activation of the subject's brain activity. Similarly, if the analysis subunit detects an increase of ≥2 points in the CRS-R score in the behavioral assessment data, it indicates an improvement in the subject's state of consciousness. If all of these requirements are met, the electrical stimulation effect on the subject is considered highly effective. If some or all results are not met, it indicates that the characteristics of brain activity activation or improvement in state of consciousness are not significant, and the electrical stimulation effect is considered ineffective.

[0049] In one example, if the analysis subunit detects an increase in the proportion of alpha waves and a decrease in the proportion of delta waves, indicating an activation trend in EEG features, and an increase in the CRS-R score of ≥2 points, indicating a significant improvement in behavioral status, then the electrical stimulation effect is determined to be highly effective; if only one of the EEG features or the behavioral score shows improvement in a single dimension, then the analysis subunit determines the electrical stimulation effect to be ineffective; if neither shows improvement, then the analysis subunit determines the electrical stimulation effect to be ineffective or ineffective.

[0050] In another example, the analysis subunit determined that the stimulus waveform provided an efficient stimulus when the subject's EEG signal showed arousal-related characteristics, such as increased gamma wave power and decreased slow wave power, and the arousal behavior scale score was significantly improved; otherwise, it was an inefficient stimulus.

[0051] In this application, the time-interference electrical stimulation system based on transnasal sphenoid electrodes further includes a control unit; the control unit controls the image acquisition and analysis unit to adjust the stimulation parameters based on the electrical stimulation effect, so that the stimulation unit adjusts the stimulation waveform generated by the stimulation region. In one example, the control unit is a control device with a processor, memory, and input / output interface, which can receive the stimulation effect evaluation results transmitted by the evaluation unit, and send parameter adjustment instructions to the image acquisition and analysis unit and / or the stimulation unit according to the results: if it is an inefficient stimulation, the stimulation time is increased or the stimulation amplitude is increased in the range of 0 to 5 mA; if it is an efficient stimulation, the current stimulation parameters can be kept unchanged.

[0052] In summary, the time-interference electrical stimulation system based on transnasal sphenoidal electrodes according to the embodiments of this application employs the synergistic effect of transnasal sphenoidal electrodes and scalp electrodes. The transnasal sphenoidal electrodes are implanted near the sphenoid sinus through the natural nasal passage, close to the midbrain reticular formation, shortening the stimulation path and reducing tissue attenuation. The scalp electrodes serve as auxiliary electrodes, forming an electric field loop with the transnasal sphenoidal electrodes. The electrode positions and stimulation parameters are optimized through brain imaging modeling and simulation to ensure that the electric field is precisely focused on the midbrain reticular formation. Combined with EEG signal monitoring and behavioral scale assessment of real-time feedback stimulation effects, accurate and safe closed-loop regulation is achieved.

[0053] The basic principles of this application have been described above with reference to specific embodiments. However, it should be noted that the advantages, benefits, and effects mentioned in this application are merely examples and not limitations, and should not be considered as essential features of each embodiment of this application. Furthermore, the specific details disclosed above are for illustrative and facilitative purposes only, and are not limitations. These details do not limit the application to the necessity of employing the aforementioned specific details for implementation.

[0054] The block diagrams of devices, apparatuses, devices, and systems involved in this application are merely illustrative examples and are not intended to require or imply that they must be connected, arranged, or configured in the manner shown in the block diagrams. As those skilled in the art will recognize, these devices, apparatuses, devices, and systems can be connected, arranged, and configured in any manner. Words such as “comprising,” “including,” “having,” etc., are open-ended terms meaning “including but not limited to,” and are used interchangeably with them. The terms “or” and “and” as used herein refer to the terms “and / or,” and are used interchangeably with them unless the context clearly indicates otherwise. The term “such as” as used herein refers to the phrase “such as but not limited to,” and is used interchangeably with it.

[0055] It should also be noted that in the apparatus, equipment, and methods of this application, the components or steps can be disassembled and / or recombined. These disassemblies and / or recombinations should be considered as equivalent solutions of this application.

[0056] The above description of the disclosed aspects is provided to enable any person skilled in the art to make or use this application. Various modifications to these aspects will be readily apparent to those skilled in the art, and the general principles defined herein can be applied to other aspects without departing from the scope of this application. Therefore, this application is not intended to be limited to the aspects shown herein, but rather to be accorded the widest scope consistent with the principles and novel features disclosed herein.

[0057] The above description has been given for purposes of illustration and description. Furthermore, this description is not intended to limit the embodiments of this application to the forms disclosed herein. Although numerous exemplary aspects and embodiments have been discussed above, those skilled in the art will recognize certain variations, modifications, alterations, additions, and sub-combinations therein.

Claims

1. A time-interference electrical stimulation system based on transnasal sphenoid sinus electrodes, characterized in that, include: The image acquisition and analysis unit acquires and fuses MRI and CT images of the subject to establish a brain model, and determines the first electrode position, second electrode position and stimulation parameters required to generate stimulation waveforms in the stimulation area based on brain model simulation. The stimulation unit includes a transnasal sphenoid sinus electrode, a scalp electrode, and a stimulation waveform generator, used to generate a stimulation waveform in the stimulation region, which is the midbrain reticular formation region. The implantation unit guides the implantation of the transnasal sphenoidal electrode at the first electrode location based on the brain model.

2. The time-interference electrical stimulation system based on transnasal sphenoid sinus electrodes according to claim 1, wherein, Based on brain model simulation, the required positions of the first and second electrodes and stimulation parameters for generating stimulation waveforms in the stimulation region include: The image acquisition and analysis unit simulates the optional stimulation waveform generated in the stimulation area when the transsphenoidal electrode and the scalp electrode have different optional electrode positions and optional stimulation parameters in the brain model. In response to an optional stimulation waveform having the highest electric field strength and / or the highest electric field focusing, the image acquisition and analysis unit sets the optional electrode position corresponding to the optional stimulation waveform as the first electrode position and the second electrode position, and sets the optional stimulation parameter as the stimulation parameter.

3. The time-interference electrical stimulation system based on transnasal sphenoid sinus electrodes according to claim 1, wherein, Based on the brain model, the transsphenoidal electrode is implanted at the first electrode location, including: The implanted unit aligns the coordinates of the brain model with the real physical coordinates through registration and alignment, so as to determine the position of the first electrode by means of the tip of the navigation needle; The implanted unit continuously monitors the navigation coordinates of the transsphenoidal electrode in the brain model through sensors to determine the true physical coordinates of the transsphenoidal electrode. The implantation unit guides the transsphenoidal electrode to the first electrode position and fixes the transsphenoidal electrode based on the first electrode position and the actual physical coordinates.

4. The time-interference electrical stimulation system based on transnasal sphenoid sinus electrodes according to claim 3, wherein, The implanted unit continuously monitors the navigation coordinates of the transsphenoidal electrode in the brain model via sensors, including: The implanted unit uses sensors to continuously collect optical or electromagnetic information emitted by the transsphenoidal electrode in order to continuously determine the navigation coordinates of the transsphenoidal electrode in the brain model.

5. The time-interference electrical stimulation system based on transnasal sphenoid sinus electrodes according to claim 1, wherein, Generating a stimulation waveform in the stimulation region includes: The stimulation waveform generator provides a first frequency fundamental electric field and a second frequency fundamental electric field to the transnasal sphenoid electrode and the scalp electrode, respectively, based on the stimulation parameters. The transnasal sphenoid sinus electrode and the scalp electrode output a first frequency fundamental electric field and a second frequency fundamental electric field at the first electrode position and the second electrode position, respectively, to generate the stimulation waveform in the stimulation area.

6. The time-interference electrical stimulation system based on transnasal sphenoid sinus electrodes according to claim 5, wherein, The transsphenoidal electrode is fixed at the first electrode position via the transsphenoidal sinus, and the scalp electrode is fixed at the second electrode position on the scalp surface; The frequency difference between the first frequency fundamental electric field and the second frequency fundamental electric field is set to 80 Hz ~ 200 Hz, and the amplitude of the stimulation waveform is set to 0 ~ 5 mA.

7. The time-interference electrical stimulation system based on transnasal sphenoid sinus electrodes according to claim 1 further includes an evaluation unit; The assessment unit acquires the subject's electroencephalogram (EEG) signals and / or clinical assessment data to analyze the electrical stimulation effect of the stimulation waveform on the stimulation area.

8. The time-interference electrical stimulation system based on transnasal sphenoid electrodes according to claim 7, wherein the assessment unit comprises an EEG signal acquisition subunit, a behavioral assessment subunit, and an analysis subunit; The EEG signal acquisition subunit acquires and processes EEG signals to obtain EEG characteristic parameters; The behavioral assessment subunit acquires and processes clinical assessment data to obtain behavioral assessment data; The analysis subunit processes the EEG characteristic parameters and behavioral assessment data to obtain the electrical stimulation effect.

9. The time-interference electrical stimulation system based on transnasal sphenoid sinus electrodes according to claim 7 further includes a control unit; The control unit controls the image acquisition and analysis unit to adjust the stimulation parameters based on the electrical stimulation effect, so that the stimulation unit adjusts the stimulation waveform generated by the stimulation region.

10. The time-interference electrical stimulation system based on transnasal sphenoid sinus electrodes according to claim 1, wherein, The stimulation unit also includes a clock timing control subunit; The clock timing control subunit adjusts the time axis of the stimulation waveform generated by the stimulation unit in the stimulation region to control the stimulation interval and stimulation time of the stimulation waveform generated by the stimulation unit in the stimulation region.

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