Full-cortex and deep-brain neural photoelectric signal synchronous detection system and method

Abstract

The invention provides a system and a method for synchronously detecting nerve photoelectric signals of a whole cortex and a deep brain. The system comprises an electrode array, a lead, a storage recording module and a microscopic system. The electrode array comprises a transparent electrode substrate and electrodes arranged on the transparent electrode substrate, and the electrode array is used for implanting the electrodes into a deep brain area of an experimental animal so as to collect deep brain nerve electrophysiological activity signals; one end of the lead is connected with the electrode array, and the other end is connected with the storage recording module; the storage recording module receives the deep brain nerve electrophysiological activity signals collected by the electrode array based on the lead, and stores the deep brain nerve electrophysiological activity signals; and the microscopic system is used for synchronously acquiring a whole cerebral cortex calcium imaging signal of the experimental animal under the condition that the electrode array acquires the deep brain nerve electrophysiological activity signal. The neural photoelectric signals of the whole cortex and the deep brain can be synchronously detected, and a foundation is laid for follow-up cross-scale multi-mode understanding of a whole brain neural activity interaction rule.

Description

Technical Field

[0001] The present invention relates to the technical field of brain-computer interfaces, and in particular, to a system and method for synchronous detection of neural optoelectronic signals in the whole cortex and deep brain. Background Art

[0002] The research on the cognitive coding mechanism of the nervous system is the core topic for revealing the high-level functions of the brain, and its research relies on the accurate analysis of the coordinated activities of the cerebral cortex and subcortical nuclei. At present, in the field of neuroscience, neural activity detection is mainly achieved through two types of technical means: microscopic imaging technology based on optical principles and electrode recording technology based on electrophysiology.

[0003] As can be known from related technologies, there are technical bottlenecks in the current technical system: optical imaging technology is limited by the strong scattering effect of brain tissue on photons, and its penetration depth usually makes it difficult to achieve real-time monitoring of deep brain nuclei with high spatio-temporal resolution; while microelectrode arrays can effectively collect the electrical signals of deep nuclei, but their spatial coverage is limited, and they cannot synchronously obtain the neural activity maps at the whole cortex scale. More critically, traditional experimental paradigms mostly adopt independent detection methods of time-sharing and zoning, and this discrete recording mode cannot meet the research needs of real-time interaction of the cortical-subcortical neural circuit during cognitive behavior.

[0004] Therefore, finding a detection system that can synchronously detect neural optoelectronic signals in the whole cortex and deep brain has become a current research hotspot. Summary of the Invention

[0005] The present invention provides a system and method for synchronous detection of neural optoelectronic signals in the whole cortex and deep brain, which can synchronously detect neural optoelectronic signals in the whole cortex and deep brain, and lay a foundation for subsequent cross-scale and multi-modal understanding of the interaction law of whole-brain neural activities.

[0006] The present invention provides a system for synchronous detection of neural optoelectronic signals in the whole cortex and deep brain. The system includes an electrode array, a lead wire, a storage and recording module, and a microscopic system. Among them, the electrode array includes a transparent electrode substrate and at least one electrode disposed on the transparent electrode substrate. The electrode array is used to implant the electrode into the deep brain region of an experimental animal to collect deep brain neuroelectrophysiological activity signals; one end of the lead wire is connected to the electrode array, and the other end of the lead wire is connected to the storage and recording module; the storage and recording module receives the deep brain neuroelectrophysiological activity signals collected by the electrode array based on the lead wire and stores the deep brain neuroelectrophysiological activity signals; the microscopic system is used to synchronously collect the calcium imaging signals of the whole brain cortex of the experimental animal when the electrode array collects the deep brain neuroelectrophysiological activity signals of the experimental animal.

[0007] A synchronous detection system for neural optoelectronic signals of the whole cortex and deep brain provided by the present invention, wherein the transparent electrode substrate is made of a transparent insulating material.

[0008] A synchronous detection system for neural optoelectronic signals of the whole cortex and deep brain provided by the present invention, wherein the transparent electrode substrate is made by bonding a transparent glass layer and a transparent polyimide layer.

[0009] A synchronous detection system for neural optoelectronic signals of the whole cortex and deep brain provided by the present invention, wherein the electrode is made of a metal material.

[0010] A synchronous detection system for neural optoelectronic signals of the whole cortex and deep brain provided by the present invention, wherein a conductive part is exposed at the tip of the electrode, and an insulating layer covers the part of the electrode except the conductive part.

[0011] A synchronous detection system for neural optoelectronic signals of the whole cortex and deep brain provided by the present invention, wherein the conductive part of the electrode is electroplated with a conductive nanomaterial.

[0012] A synchronous detection system for neural optoelectronic signals of the whole cortex and deep brain provided by the present invention, wherein the conductive part of the electrode is modified with a biocompatible gel material.

[0013] A synchronous detection system for neural optoelectronic signals of the whole cortex and deep brain provided by the present invention, wherein the tip diameter of the electrode is less than or equal to 30 μm.

[0014] A synchronous detection system for neural optoelectronic signals of the whole cortex and deep brain provided by the present invention, wherein the length of the conductive part exposed at the tip of the electrode is less than or equal to 50 μm.

[0015] The present invention also provides a method for synchronous detection of neural optoelectronic signals of the whole cortex and deep brain. The method is applied to the synchronous detection system for neural optoelectronic signals of the whole cortex and deep brain described in any one of the above, and the method includes: obtaining a synchronous detection instruction for neural optoelectronic signals, wherein the synchronous detection instruction for neural optoelectronic signals is used to indicate obtaining deep brain neuroelectrophysiological activity signals and whole brain cortex calcium imaging signals of an experimental animal during a stimulation experiment; based on the synchronous detection instruction for neural optoelectronic signals, during the stimulation experiment of the experimental animal, based on the synchronous detection system for neural optoelectronic signals of the whole cortex and deep brain, synchronously detect the deep brain neuroelectrophysiological activity signals and the whole brain cortex calcium imaging signals of the experimental animal in real time, wherein the stimulation experiment at least includes: an experiment in which the experimental animal receives visual and auditory stimuli, and an experiment in which the experimental animal receives response action punishment and / or response action reward, wherein the response action punishment and / or the response action reward are determined according to the response actions made by the experimental animal to the received visual and auditory stimuli.

[0016] The present invention also provides a virtual device for synchronous detection of neural optoelectronic signals in the whole cortex and deep brain. The virtual device is applied to the synchronous detection system of neural optoelectronic signals in the whole cortex and deep brain according to any one of the above. The virtual device includes: an acquisition module, configured to acquire a synchronous detection instruction for neural optoelectronic signals, wherein the synchronous detection instruction for neural optoelectronic signals is used to indicate acquiring deep brain neuroelectrophysiological activity signals and whole-brain cortical calcium imaging signals of an experimental animal during a stimulation experiment; a detection module, configured to, based on the synchronous detection instruction for neural optoelectronic signals, during the stimulation experiment of the experimental animal, synchronously detect in real time the deep brain neuroelectrophysiological activity signals and the whole-brain cortical calcium imaging signals of the experimental animal based on the synchronous detection system of neural optoelectronic signals in the whole cortex and deep brain, wherein the stimulation experiment at least includes: an experiment in which the experimental animal receives visual and auditory stimuli, and an experiment in which the experimental animal receives response action punishment and / or response action reward, wherein the response action punishment and / or the response action reward are determined according to the response actions made by the experimental animal to the received visual and auditory stimuli.

[0017] The present invention also provides an electronic device, including a memory, a processor, and a computer program stored on the memory and executable on the processor. When the processor executes the computer program, the method for synchronous detection of neural optoelectronic signals in the whole cortex and deep brain as described in any one of the above is implemented.

[0018] The present invention also provides a non-transitory computer-readable storage medium, on which a computer program is stored. When the computer program is executed by a processor, the method for synchronous detection of neural optoelectronic signals in the whole cortex and deep brain as described in any one of the above is implemented.

[0019] The present invention also provides a computer program product, including a computer program. When the computer program is executed by a processor, the method for synchronous detection of neural optoelectronic signals in the whole cortex and deep brain as described in any one of the above is implemented.

[0020] The full-cortex and deep-brain neural optoelectronic signal synchronous detection system and method provided by the present invention, the system includes an electrode array, a lead wire, a storage and recording module, and a microscopic system. Among them, the electrode array includes a transparent electrode substrate and at least one electrode disposed on the transparent electrode substrate. The electrode array is used to implant the electrode into the deep-brain region of an experimental animal to collect deep-brain neuroelectrophysiological activity signals; one end of the lead wire is connected to the electrode array, and the other end of the lead wire is connected to the storage and recording module; the storage and recording module receives the deep-brain neuroelectrophysiological activity signals collected by the electrode array based on the lead wire and stores the deep-brain neuroelectrophysiological activity signals; the microscopic system is used to synchronously collect the full-brain cortex calcium imaging signals of the experimental animal when the electrode array collects the deep-brain neuroelectrophysiological activity signals of the experimental animal. It realizes the ability to synchronously detect the neural optoelectronic signals of the full cortex and deep brain, laying a foundation for subsequent cross-scale multimodal understanding of the interaction law of the whole-brain neural activity. Description of the Drawings

[0021] In order to more clearly illustrate the technical solutions in the present invention or the prior art, the following will briefly introduce the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings in the following description are some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0022] Figure 1 It is a schematic structural diagram of the full-cortex and deep-brain neural optoelectronic signal synchronous detection system provided by the present invention.

[0023] Figure 2 It is one of the schematic structural diagrams of the electrode array provided by the present invention.

[0024] Figure 3 It is another schematic structural diagram of the electrode array provided by the present invention.

[0025] Figure 4 It is a schematic flow diagram of the full-cortex and deep-brain neural optoelectronic signal synchronous detection method provided by the present invention.

[0026] Figure 5 It is a schematic structural diagram of the full-cortex and deep-brain neural optoelectronic signal synchronous detection virtual device provided by the present invention.

[0027] Figure 6 It is a schematic structural diagram of the electronic device provided by the present invention.

[0028] Reference Signs: 100: Full-cortex and deep-brain neural optoelectronic signal synchronous detection system; 110: Electrode array; 120: Lead wire; 130: Storage and recording module; 140: Microscopic system; 111: Electrode; 112: Transparent electrode substrate; 1121: Transparent glass layer; 1122: Transparent polyimide layer; 1111: Conductive part; 1112: Insulating layer. Specific embodiments

[0029] To make the objectives, technical solutions and advantages of the present invention clearer, the technical solutions in the present invention will be clearly and completely described below with reference to the accompanying drawings in the present invention. Apparently, the described embodiments are some, but not all, of the embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art based on the embodiments in the present invention without making creative efforts shall fall within the protection scope of the present invention.

[0030] The whole cortex and deep brain neural optoelectronic signal synchronous detection system provided by the present invention can achieve cross-scale high-precision synchronous detection and recording of cortical-deep brain nerve activities, so as to effectively obtain high-throughput nerve activity interaction response characteristics of multiple brain regions. The whole cortex and deep brain neural optoelectronic signal synchronous detection system provided by the present invention can also help those skilled in the art to analyze the basic brain function mechanisms of the brain nervous system, such as cognition, memory, sleep, etc., from the mesoscopic scale, and provide a new and efficient technical means for understanding the interaction law of whole brain nerve activities in a cross-scale and multimodal manner, thus having great significance for deeply explaining the cognitive coding law of the nervous system.

[0031] Figure 1 is a schematic structural diagram of the whole cortex and deep brain neural optoelectronic signal synchronous detection system provided by the present invention; Figure 2 is one of the schematic structural diagrams of the electrode array provided by the present invention.

[0032] The following will be combined with Figure 1 and Figure 2 to illustrate the structure of the whole cortex and deep brain neural optoelectronic signal synchronous detection system provided by the present invention.

[0033] In an exemplary embodiment of the present invention, in combination with Figure 1 it can be seen that the whole cortex and deep brain neural optoelectronic signal synchronous detection system 100 may include an electrode array 110, a lead 120, a storage and recording module 130, and a microscopy system 140. Each module will be introduced separately below.

[0034] In one embodiment, the electrode array 110 may include a transparent electrode substrate 112 and at least one electrode 111 disposed on the transparent electrode substrate 112. Among them, the electrode array 110 is used to implant the electrode 111 into the deep brain region of an experimental animal to collect deep brain nerve electrophysiological activity signals.

[0035] In one embodiment, the length of the electrode 111 can be determined according to the actual situation. During application, microelectromechanical technology can be used to form a three-dimensional structure, with a customizable length and nerve detection electrode sites that match the entire cerebral cortex, namely the electrode 111, thus laying a foundation for the synchronous recording of cortical neural calcium imaging and subcortical neuroelectrophysiology.

[0036] In another embodiment, taking an experimental animal as a mouse for example, in order to match the acquisition of deep brain neuroelectrophysiological activity signals of the experimental animal mouse, 48 electrophysiological detection sites, namely the electrode 111, can be set. These are arranged according to the brain region division of the cerebral cortex of the experimental animal mouse, and the monitoring sites cover the entire cortical region. It can be understood that the number of electrodes 111 arranged on the transparent electrode substrate 112 can be determined according to the brain region division of the cerebral cortex of the experimental animal to be implanted, and no specific limitation is made in this embodiment.

[0037] In yet another embodiment, the deep brain region can include sublayers I - VI of the cerebral cortex and deep brain nuclei. Based on the electrode array 110, the acquisition of electrophysiological signals from sublayers I - VI of the cerebral cortex and deep brain nuclei can be achieved.

[0038] It should be noted that in this embodiment, the transparent electrode substrate 112 is set to be transparent, so as not to affect the imaging effect of the microscopic system 140, and further to lay a foundation for the synchronous acquisition of optoelectronic nerve activities in the entire cerebral cortex and subcortex, providing an effective tool for carrying out cross-scale multimodal neurocognitive activity research. In other words, setting the transparent electrode substrate 112 to be transparent can ensure high-resolution cortical neural activity calcium imaging (corresponding to the calcium imaging signal of the entire cerebral cortex).

[0039] In yet another embodiment, one end of the lead 120 can be connected to the electrode array 110, and the other end of the lead 120 is connected to the storage and recording module 130. Since the electrode array 110 is used to be implanted into the deep brain region of the experimental animal to collect deep brain neuroelectrophysiological activity signals, the deep brain neuroelectrophysiological activity signals collected can be transmitted through the lead to the storage and recording module 130 for storage. That is, the storage and recording module 130 receives the deep brain neuroelectrophysiological activity signals collected by the electrode array 110 based on the lead 120 and stores the deep brain neuroelectrophysiological activity signals.

[0040] In yet another embodiment, the microscopic system 140 is used to synchronously collect the calcium imaging signals of the whole brain cortex of an experimental animal while the electrode array 110 collects the deep brain nerve electrophysiological activity signals of the experimental animal. Among them, the microscopic system 140 can be the calcium activity imaging of the whole cortex neurons. In this embodiment, the microscopic system 140 is not specifically limited. Since the transparent electrode substrate 112 of the electrode array 110 is set to be transparent, the imaging effect of the microscopic system 140 can be not affected. When in use, it can not only display the calcium imaging activity of the whole brain cortex, but also synchronously obtain the electrophysiological activities of each sublayer under the cortex. The electrode detection sites of different lengths are distributed in multiple subregions of the cortex, and can reflect the information interaction and coordinated coding between brain regions in real time.

[0041] The neural optoelectronic signal synchronous detection system 100 for the whole cortex and deep brain provided by the present invention, the system includes an electrode array 110, a lead wire 120, a storage and recording module 130, and a microscopic system 140. Among them, the electrode array 110 includes a transparent electrode substrate 112 and at least one electrode 111 disposed on the transparent electrode substrate 112. The electrode array 110 is used to implant the electrode 111 into the deep brain region of an experimental animal to collect deep brain nerve electrophysiological activity signals; one end of the lead wire 120 is connected to the electrode array 110, and the other end of the lead wire 120 is connected to the storage and recording module 130; the storage and recording module 130 receives the deep brain nerve electrophysiological activity signals collected by the electrode array 110 based on the lead wire 120, and stores the deep brain nerve electrophysiological activity signals; the microscopic system 140 is used to synchronously collect the calcium imaging signals of the whole brain cortex of the experimental animal when the electrode array 110 collects the deep brain nerve electrophysiological activity signals of the experimental animal. It realizes the synchronous detection of neural optoelectronic signals of the whole cortex and deep brain, and lays a foundation for the subsequent cross-scale multi-modal understanding of the interaction law of whole brain nerve activities.

[0042] In yet another exemplary embodiment of the present invention, the transparent electrode substrate 112 can be made of a transparent insulating material. It can be understood that the transparent electrode substrate 112 can also be replaced with other materials with high transparency and not affecting imaging.

[0043] Figure 3 It is the second structural schematic diagram of the electrode array provided by the present invention.

[0044] Next, in combination with Figure 3 the structure of the electrode array will be described.

[0045] In yet another exemplary embodiment of the present invention, in combination with Figure 3 it can be known that the transparent electrode substrate 112 can be made by bonding a transparent glass layer 1121 and a transparent polyimide layer 1122. It can be understood that in Figure 3In this case, the transparent glass layer 1121 and the transparent polyimide layer 1122 can form the transparent electrode substrate 112. By bonding the transparent glass layer 1121 and the transparent polyimide layer 1122 to fabricate the transparent electrode substrate 112, it can effectively ensure that the imaging effect of the microscopic system 140 is not affected. Furthermore, when using the whole cortex and deep brain neural optoelectronic signal synchronous detection system 100, it can not only display the calcium imaging activity of the whole brain cortex, but also synchronously acquire the neuroelectrophysiological activities of each sublayer under the cortex, achieving the ability to synchronously detect the neural optoelectronic signals of the whole cortex and deep brain, laying a foundation for subsequent cross-scale multimodal understanding of the interaction law of whole brain neural activities.

[0046] In another exemplary embodiment of the present invention, the electrode 111 can be made of a metal material. In another example, the electrode 111 can be made of the gold Au material.

[0047] It can be understood that since the electrode 111 can be made of a metal material, the electrode 111 can also be used as an electrical stimulation electrode to apply electrical stimulation regulation to the subcortical and deep brain nuclei, realizing the integration of the detection function and the regulation function. In another example, the electrode 111 can also be made of a metal material with good biocompatibility, so as to ensure that the implantation of the electrode 111 will not have an adverse effect on the experimental animals.

[0048] In another exemplary embodiment of the present invention, continuing with the combination of Figure 3 for illustration, the tip of the electrode 111 exposes a conductive part 1111, and the part of the electrode 111 other than the conductive part 1111 is covered with an insulating layer 1112. It can be understood that covering the part of the electrode 111 other than the conductive part 1111 with the insulating layer 1112 can effectively avoid crosstalk of external signals.

[0049] In another exemplary embodiment of the present invention, the conductive part 1111 of the electrode 111 is electroplated with a conductive nanomaterial. During the application process, by electroplating the conductive part 1111 of the electrode 111 with a conductive nanomaterial, the conductivity of the electrode 111 can be enhanced, and the detection signal-to-noise ratio can be improved, so that the neural optoelectronic signals of the whole cortex and deep brain with a higher signal-to-noise ratio (including deep brain neuroelectrophysiological activity signals and whole brain cortex calcium imaging signals) can be synchronously detected, laying a foundation for subsequent cross-scale multimodal understanding of the interaction law of whole brain neural activities.

[0050] In another exemplary embodiment of the present invention, the conductive part 1111 of the electrode 111 is modified with a biocompatible gel material. During the application process, by modifying the conductive part 1111 of the electrode 111 with a biocompatible gel material, the proliferation of biological tissues can be minimized.

[0051] In the foregoing embodiments, to avoid the high impedance problem caused by micro-scale detection electrodes, other conductive materials, nano-materials or anti-tissue inflammation materials are used to modify the surface of electrode 111 through coating, cross-linking and electroplating, etc., which can further reduce the electrode impedance, reduce the detection phase delay, and increase the biocompatibility between the electrode and the tissue.

[0052] In another exemplary embodiment of the present invention, the tip diameter of electrode 111 can be set to be less than or equal to 30 μm. By setting the tip diameter of electrode 111 to be less than or equal to 30 μm, the tissue wound of the experimental animal can be effectively reduced, and thus the normal activities of the experimental action are not affected.

[0053] In another exemplary embodiment of the present invention, the length of the conductive part 1111 exposed at the tip of electrode 111 can be set to be less than or equal to 50 μm. By setting the length of the conductive part 1111 exposed at the tip of electrode 111 to be less than or equal to 50 μm, the mutual crosstalk between signals can be effectively reduced, and the accuracy of the neuro-optical signals of the entire cortex and deep brain collected (including the deep brain neuroelectrophysiological activity signals and the whole brain cortex calcium imaging signals) can be improved.

[0054] In another embodiment, the tip diameter of electrode 111 can be 10 μm, and the length of the conductive part 1111 exposed at the tip can be 30 μm. The height distribution of electrode 111 can be between hundreds of micrometers and millimeters. Specifically, the tip diameter, the exposed length of the conductive layer (corresponding to the length of the conductive part 1111), and the height of electrode 111 can be customized according to the position of the brain region to be detected, and can be distributed in each sublayer of cortical layers I-VI and deep brain nuclei, so as to ensure high-precision multi-nucleus neuroelectrical activity detection across scales while minimizing signal crosstalk.

[0055] To further introduce the neuro-optical signal synchronous detection system 100 for the entire cortex and deep brain provided by the present invention, the process of manufacturing the electrode array 110 will be described below.

[0056] In one embodiment, laser micromachining technology and microelectromechanical technology can be used to process the electrode array 110. Among them, a conical three-dimensional structure can be formed on polydimethylsiloxane (PDMS) using laser micromachining technology, and the height dimensions of electrodes 111 with different lengths can be formed by controlling the depth of laser processing, so as to obtain a formed PDMS template. Further, a transparent polyimide (CPI) can be spin-coated on the formed PDMS template to form a three-dimensional electrode base; after bonding the glass substrate with CPI, the PDMS and CPI are demolded to expose the sites of electrodes 111.

[0057] Further, photoresist can be spin-coated on the front side of the electrode 111, lithography can be performed using a mask, and the photoresist at the sites, leads, and pads of the electrode 111 can be removed; then, metal Au can be sputtered on the surface of the electrode 111 to form a conductive layer and the photoresist can be stripped; further, the conductive part 1111 can be exposed at the tip of the electrode 111, and photosensitive polyimide (PSPI) can be spin-coated on the part of the electrode 111 other than the conductive part 1111 as the insulating layer 1112. Finally, the prepared electrode array 110 can be encapsulated by thermocompression bonding or the like to complete the preparation of the electrode array 110.

[0058] As can be seen from the foregoing description, the full-cortex and deep-brain neural optoelectronic signal synchronous detection system provided by the present invention can synchronously collect high-throughput cortical fluorescence calcium activity and high-precision deep-brain nucleus electrophysiological activity, providing a neural activity detection tool with both detection breadth and depth, high spatio-temporal resolution, and good biocompatibility, and providing new technical support for large-scale research on neural activity coding mechanisms.

[0059] Based on the same inventive concept, the present invention also provides a full-cortex and deep-brain neural optoelectronic signal synchronous detection method, which will be described below in conjunction with the following embodiments.

[0060] Figure 4 It is a schematic flow chart of the full-cortex and deep-brain neural optoelectronic signal synchronous detection method provided by the present invention.

[0061] In another exemplary embodiment of the present invention, the full-cortex and deep-brain neural optoelectronic signal synchronous detection method can be applied to the full-cortex and deep-brain neural optoelectronic signal synchronous detection system described in any of the foregoing embodiments. Combining Figure 4 it can be seen that the full-cortex and deep-brain neural optoelectronic signal synchronous detection method can include step 410 and step 420, and each step will be introduced separately below.

[0062] In step 410, a neural optoelectronic signal synchronous detection instruction is obtained, where the neural optoelectronic signal synchronous detection instruction is used to indicate obtaining deep-brain neuroelectrophysiological activity signals and whole-brain cortical calcium imaging signals of an experimental animal during a stimulation experiment. In step 420, based on the neural optoelectronic signal synchronous detection instruction, during the stimulation experiment of the experimental animal, the deep-brain neuroelectrophysiological activity signals and the whole-brain cortical calcium imaging signals of the experimental animal are synchronously detected in real time based on the full-cortex and deep-brain neural optoelectronic signal synchronous detection system, where the stimulation experiment at least includes: an experiment in which the experimental animal receives visual and auditory stimuli, and An experiment in which an experimental animal receives response action punishment and / or response action reward, wherein the response action punishment and / or response action reward are determined according to the response actions made by the experimental animal to the received audiovisual stimuli.

[0063] In one embodiment, based on the received neuro-optical signal synchronization detection instruction, during the stimulation experiment on the experimental animal, the deep brain neuroelectrophysiological activity signal and the whole brain cortex calcium imaging signal of the experimental animal are synchronously detected in real time based on the neuro-optical signal synchronous detection system of the whole cortex and deep brain. Among them, the stimulation experiment can at least include: an experiment in which the experimental animal receives audiovisual stimuli, and an experiment in which the experimental animal receives response action punishment and / or response action reward, wherein the response action punishment and / or response action reward are determined according to the response actions made by the experimental animal to the received audiovisual stimuli. During the application process, a visual stimulus display screen or an auditory stimulus player can be used to show visual or auditory stimuli, that is, audiovisual stimuli, to the experimental animal.

[0064] In another embodiment, a water supply device can be used to provide sugar water to the experimental animal as a response action reward; a jet device can be used to apply jet stimulation to the experimental animal as a response punishment. During the application process, a video playback pulley can be set, which can be driven by the left and right sliding of the front paws of the experimental animal, such as a mouse, to allow the mouse to autonomously select the type of played image, and a mileage recorder can be used to record the distance that the mouse moves the pulley, wherein the distance that the mouse moves the pulley is associated with the video playback, and this can be used as a response action to the audiovisual stimuli.

[0065] Furthermore, the neuro-optical signal synchronous detection system of the whole cortex and deep brain is further called to synchronously detect the deep brain neuroelectrophysiological activity signal and the whole brain cortex calcium imaging signal in real time during the whole process of the above-mentioned stimulation experiment on the experimental animal. Thus, the behavior of the experimental animal can be evaluated and fed back in real time, and real biological neural activity data can be obtained through cross-scale neural activity monitoring, and the cognitive behavior of the experimental animal can be reshaped by combining multi-modal regulation means, providing new ideas for deeply understanding the coding rules of nervous system cognitive activities.

[0066] Next, the virtual device for synchronous detection of neuro-optical signals of the whole cortex and deep brain provided by the present invention will be described. The virtual device for synchronous detection of neuro-optical signals of the whole cortex and deep brain described below can be mutually referred to corresponding to the method for synchronous detection of neuro-optical signals of the whole cortex and deep brain described above.

[0067] Figure 5 It is a schematic structural diagram of the virtual device for synchronous detection of neuro-optical signals of the whole cortex and deep brain provided by the present invention.

[0068] Next, it will be combined with Figure 5Describe the structure of the virtual device for synchronous detection of neural optoelectronic signals in the whole cortex and deep brain.

[0069] In an exemplary embodiment of the present invention, the virtual device for synchronous detection of neural optoelectronic signals in the whole cortex and deep brain can be applied to the system for synchronous detection of neural optoelectronic signals in the whole cortex and deep brain described in any of the foregoing embodiments. Combining Figure 5 it can be seen that the virtual device for synchronous detection of neural optoelectronic signals in the whole cortex and deep brain may include an acquisition module 510 and a detection module 520. Each module will be introduced separately below.

[0070] The acquisition module 510 can be configured to obtain a neural optoelectronic signal synchronous detection instruction, wherein the neural optoelectronic signal synchronous detection instruction is used to indicate obtaining the deep brain neuroelectrophysiological activity signal and the whole brain cortex calcium imaging signal of an experimental animal during a stimulation experiment; The detection module 520 can be configured to, based on the neural optoelectronic signal synchronous detection instruction, during the process of the experimental animal performing a stimulation experiment, synchronously detect in real time the deep brain neuroelectrophysiological activity signal and the whole brain cortex calcium imaging signal of the experimental animal based on the system for synchronous detection of neural optoelectronic signals in the whole cortex and deep brain, wherein the stimulation experiment at least includes: An experiment in which the experimental animal receives visual and auditory stimuli, and An experiment in which the experimental animal receives response action punishment and / or response action reward, wherein the response action punishment and / or the response action reward are determined according to the response action of the experimental animal to the received visual and auditory stimuli.

[0071] Figure 6 Illustrates a schematic physical structure diagram of an electronic device, such as Figure 6As shown, the electronic device may include: a processor 610, a communications interface 620, a memory 630, and a communication bus 640. Among them, the processor 610, the communications interface 620, and the memory 630 complete communication with each other through the communication bus 640. The processor 610 may call the logical instructions in the memory 630 to execute the method for synchronous detection of neural optoelectronic signals in the whole cortex and deep brain. The method is applied to the system for synchronous detection of neural optoelectronic signals in the whole cortex and deep brain described in any one of the above, and the method includes: obtaining a synchronous detection instruction for neural optoelectronic signals, where the synchronous detection instruction for neural optoelectronic signals is used to indicate obtaining the deep brain neuroelectrophysiological activity signal and the whole brain cortex calcium imaging signal of an experimental animal during a stimulation experiment; based on the synchronous detection instruction for neural optoelectronic signals, during the stimulation experiment of the experimental animal, based on the system for synchronous detection of neural optoelectronic signals in the whole cortex and deep brain, synchronously detect the deep brain neuroelectrophysiological activity signal and the whole brain cortex calcium imaging signal of the experimental animal in real time, where the stimulation experiment at least includes: an experiment in which the experimental animal receives visual and auditory stimuli, and an experiment in which the experimental animal receives response action punishment and / or response action reward, where the response action punishment and / or the response action reward are determined according to the response action made by the experimental animal to the received visual and auditory stimuli.

[0072] In addition, when the logical instructions in the above-mentioned memory 630 are implemented in the form of software functional units and sold or used as independent products, they can be stored in a computer-readable storage medium. Based on such an understanding, the technical solution of the present invention, in essence, or the part that contributes to the prior art, or a part of this technical solution, can be embodied in the form of a software product. The computer software product is stored in a storage medium and includes several instructions for causing a computer device (which may be a personal computer, a server, or a network device, etc.) to execute all or part of the steps of the methods described in various embodiments of the present invention. The foregoing storage medium includes: various media such as USB flash drives, mobile hard disks, read-only memories (ROM, Read-Only Memory), random access memories (RAM, Random Access Memory), magnetic disks, or optical discs that can store program codes.

[0073] On the other hand, the present invention also provides a computer program product, which includes a computer program. The computer program can be stored on a non-transitory computer-readable storage medium. When the computer program is executed by a processor, the computer can execute the method for synchronously detecting neural optoelectronic signals of the whole cortex and deep brain provided by each of the above methods. The method is applied to any one of the systems for synchronously detecting neural optoelectronic signals of the whole cortex and deep brain, and the method includes: obtaining a neural optoelectronic signal synchronous detection instruction, where the neural optoelectronic signal synchronous detection instruction is used to indicate obtaining deep brain neuroelectrophysiological activity signals and whole brain cortex calcium imaging signals of an experimental animal during a stimulation experiment; based on the neural optoelectronic signal synchronous detection instruction, during the stimulation experiment of the experimental animal, based on the system for synchronously detecting neural optoelectronic signals of the whole cortex and deep brain, synchronously detecting in real time the deep brain neuroelectrophysiological activity signals and the whole brain cortex calcium imaging signals of the experimental animal, where the stimulation experiment at least includes: an experiment in which the experimental animal receives visual and auditory stimuli, and an experiment in which the experimental animal receives response action punishment and / or response action reward, where the response action punishment and / or the response action reward are determined according to the response actions made by the experimental animal to the received visual and auditory stimuli.

[0074] In yet another aspect, the present invention also provides a non-transitory computer-readable storage medium, on which a computer program is stored. When the computer program is executed by a processor, it realizes the method for synchronously detecting neural optoelectronic signals of the whole cortex and deep brain provided by each of the above methods. The method is applied to any one of the systems for synchronously detecting neural optoelectronic signals of the whole cortex and deep brain, and the method includes: obtaining a neural optoelectronic signal synchronous detection instruction, where the neural optoelectronic signal synchronous detection instruction is used to indicate obtaining deep brain neuroelectrophysiological activity signals and whole brain cortex calcium imaging signals of an experimental animal during a stimulation experiment; based on the neural optoelectronic signal synchronous detection instruction, during the stimulation experiment of the experimental animal, based on the system for synchronously detecting neural optoelectronic signals of the whole cortex and deep brain, synchronously detecting in real time the deep brain neuroelectrophysiological activity signals and the whole brain cortex calcium imaging signals of the experimental animal, where the stimulation experiment at least includes: an experiment in which the experimental animal receives visual and auditory stimuli, and an experiment in which the experimental animal receives response action punishment and / or response action reward, where the response action punishment and / or the response action reward are determined according to the response actions made by the experimental animal to the received visual and auditory stimuli.

[0075] The device embodiments described above are merely illustrative. The units described as separate components may or may not be physically separated, and the components shown as units may or may not be physical units, that is, they may be located in one place or distributed to multiple network units. Some or all of the modules can be selected according to actual needs to achieve the purpose of the solution of this embodiment. Those of ordinary skill in the art can understand and implement it without creative effort.

[0076] Through the description of the above embodiments, those skilled in the art can clearly understand that each embodiment can be implemented by means of software plus a necessary general hardware platform, and of course, it can also be implemented by hardware. Based on this understanding, the essence of the above technical solution, or the part that contributes to the prior art, can be embodied in the form of a software product. This computer software product can be stored in a computer-readable storage medium, such as ROM / RAM, magnetic disk, optical disk, etc., and includes several instructions to enable a computer device (which can be a personal computer, server, or network device, etc.) to execute the methods described in each embodiment or some parts of the embodiments.

[0077] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit them. Although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that they can still modify the technical solutions described in the foregoing embodiments, or perform equivalent replacements for some of the technical features. However, these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A neural optoelectronic signal synchronous detection system for the whole cortex and deep brain, characterized in that, The system includes an electrode array, leads, a storage and recording module, and a microscopy system. Among them, the electrode array includes a transparent electrode substrate and at least one electrode disposed on the transparent electrode substrate. The electrode array is used to implant the electrode into the deep brain region of an experimental animal to collect deep brain neuroelectrophysiological activity signals; one end of the lead is connected to the electrode array, and the other end of the lead is connected to the storage and recording module; the storage and recording module receives the deep brain neuroelectrophysiological activity signals collected by the electrode array based on the lead and stores the deep brain neuroelectrophysiological activity signals; the microscopy system is used to synchronously collect the whole brain cortical calcium imaging signals of the experimental animal when the electrode array collects the deep brain neuroelectrophysiological activity signals of the experimental animal.

2. The neuro-optical and electrical signal synchronous detection system for the whole cortex and deep brain according to claim 1, wherein The transparent electrode substrate is made of a transparent insulating material.

3. The synchronous detection system for neural optoelectronic signals of the entire cerebral cortex and deep brain according to claim 2, characterized in that, The transparent electrode substrate is made by bonding a transparent glass layer and a transparent polyimide layer.

4. The synchronous detection system for neural optoelectronic signals of the whole cortex and deep brain according to claim 1, wherein The electrode is made of a metal material.

5. The neuro-optoelectronic signal synchronous detection system for the whole cortex and deep brain according to claim 4, characterized in that The tip of the electrode exposes a conductive portion, and the portion of the electrode other than the conductive portion is covered with an insulating layer.

6. The full-cortex and deep-brain neural optoelectronic signal synchronous detection system according to claim 5, wherein The conductive portion of the electrode is electroplated with a conductive nanomaterial.

7. The neuro-optical and electrical signal synchronous detection system for the whole cortex and deep brain according to claim 5, wherein The conductive portion of the electrode is modified with a biocompatible gel material.

8. The whole cortex and deep brain neural optoelectronic signal synchronous detection system according to any one of claims 1 to 7, characterized in that, The tip diameter of the electrode is less than or equal to 30 um.

9. The whole cortex and deep brain neural optoelectronic signal synchronous detection system according to any one of claims 1 to 7, characterized in that, The length of the conductive portion exposed at the tip of the electrode is less than or equal to 50 um.

10. A method for synchronous detection of neural optoelectronic signals in the whole cortex and deep brain, characterized in that, The method is applied to the synchronous detection system for neuro-optical signals of the whole cortex and deep brain according to any one of claims 1 to 9. The method includes: obtaining a synchronous detection instruction for neuro-optical signals, where the synchronous detection instruction for neuro-optical signals is used to indicate obtaining deep brain neuroelectrophysiological activity signals and whole brain cortical calcium imaging signals of an experimental animal during a stimulation experiment; based on the synchronous detection instruction for neuro-optical signals, during the stimulation experiment of the experimental animal, the deep brain neuroelectrophysiological activity signals and the whole brain cortical calcium imaging signals of the experimental animal are synchronously detected in real time based on the synchronous detection system for neuro-optical signals of the whole cortex and deep brain. Among them, the stimulation experiment at least includes: an experiment in which the experimental animal receives visual and auditory stimuli, and an experiment in which the experimental animal receives response action punishment and / or response action reward, where the response action punishment and / or the response action reward are determined according to the response actions made by the experimental animal to the received visual and auditory stimuli.

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