Personalized brain stimulation device

Abstract

To provide a personalized brain stimulation device.SOLUTION: A personalized brain stimulation device includes: a sensor unit measuring biological information of an object; a control unit determining, based on the biological information of the object measured by the sensor unit, that the state of the object corresponds to a first state among a predetermined plurality of depression-related states; and a stimulation unit delivering a stimulus, which varies according to the first state determined from the control unit, to the brain of the object to entrain synchronized oscillation in multiple regions of the brain of the object, wherein the stimulus is a first stimulus to entrain gamma oscillation, a second stimulus to entrain any one of delta, theta, alpha, and beta oscillation, or a third stimulus that combines the first stimulus and the second stimulus, wherein a transcranial alternating current stimulation may be a first composite stimulation in which ON / OFF is repeated according to a first frequency, and a signal turned ON according to the first frequency is applied as a stimulation according to a second frequency.SELECTED DRAWING: Figure 5

Description

Technical Field

[0001] The present invention relates to an individualized brain stimulation device. More specifically, it relates to an individualized brain stimulation device capable of determining a patient's depressive state based on the patient's biological information and transmitting a combined stimulation based on tACS (Transcranial Alternating Current Stimulation) to the patient's brain to improve the patient's depressive state.

Background Art

[0002] In recent years, there has been a shift to an era of treating diseases with electronic medicine rather than oral medicine. Electronic medicine refers to medical devices that exert new therapeutic effects by applying energies such as electricity, magnetic fields, and ultrasonic waves to the cranial nerves, rather than inducing symptom relief through biochemical actions in the human body like pharmaceuticals. It is mainly regarded as a new field of miniaturized medical devices related to the regulation of cranial nerve function.

[0003] Moreover, electronic medicine is an electronic device that can treat diseases by means of electrical stimulation without directly injecting drugs into the patient's body. Since it can select and stimulate only specific sites that require treatment, it has the advantage of being safe for the human body. That is, patients who are resistant to taking drugs can reduce side effects by replacing them with electronic medicine treatment, and can also obtain a synergistic effect of treatment by combining with drugs.

[0004] Furthermore, among electronic drugs in Japan, an antidepressant electronic drug that treats depression by normalizing the prefrontal lobe function that causes depression has been put on the market. As methods of stimulating electronic drugs for treating depression, there are tACS (transcranial Alternating Current Stimulation), tDCS (transcranial Direct Current Stimulation), DBS (Deep Brain Stimulation), tMS (transcranial Magnetic Stimulation), ECT (ElectroConvulsive Therapy), and others.

[0005] First, tACS is a method of transmitting a minute current of less than 1 mA to the skull by attaching electrodes. It is used for non-drug treatments that improve symptoms such as anxiety, depression, insomnia, stress, headache, and various types of pain. It is effective in regulating microglial cells, is safe using minute current, has no side effects, and thus enables medium- to long-term treatment. Additionally, as a state-of-the-art treatment method highly compatible with existing chemotherapy that promotes and / or suppresses hormone secretion, it is possible to induce sleep and improve the quality of sleep by maintaining the stable DMN of the brain itself, and it is possible to induce sleep and improve the quality of sleep through the improvement of hormones (such as serotonin, melatonin, and GABA). And it can stimulate brain tissue to restore the neurochemical substances to the balance before stress. Such tACS stimulation energy is AC (current flow), the stimulation form is pulse and sinusoidal, the mechanism is entrainment of the brain by current, and the advantage is that its safety has been verified (0.5 mA or 500 μA), which is convenient for patients. However, due to skin impedance, which is a value that impedes the flow of current when voltage is applied in the circuit, there is no pain, but there is a disadvantage that the stimulation transmission is weak and it is difficult to feel the stimulation.

[0006] tDCS is a method of stimulating neurons in the cerebral cortex with a weak direct current by attaching electrodes to the head. It is a non-invasive brain stimulation method for the recovery of sequelae caused by brain damage, and can help improve brain function by adjusting the active state of cranial nerves through electrical stimulation. Such tDCS stimulation energy is DC (electric field), the stimulation form is direct current (DC), the mechanism is to maintain balance by activating (+) / inhibiting (-) charges at the electrode position, and the advantage is that it can be applied with a simple configuration (2 mA). However, since the difference between actual stimulation and sham stimulation is not large, there is a disadvantage that the therapeutic effect for depression is low. Although it is a non-invasive stimulation with simple treatment, there is a risk of burns at the electrode attachment site.

[0007] DBS is a method of stimulating the activity of neurons by placing a fine electrode needle in the deep nuclear region of the brain. By applying electrical stimulation to the nucleus of a specific brain region, it is possible to treat and improve various diseases including movement disorders by interfering with the pathological signals generated in the brain region. Also, by placing a fine electrode in the deep nuclear region of the brain and supplying the power required for activity from a pulse generator inserted into the chest in a manner similar to a cardiac pacemaker, depolarization can be blocked, that is, the nerve output of the neurons located at the electrode site can be blocked. And synaptic inhibition, that is, by activating the axon terminals with synaptic connections to the neurons near the electrode, the output of the neurons can be indirectly adjusted. Such DBS stimulation energy is direct current (DC), pulse, and near-infrared (NIR), the stimulation form is pulse and sine wave, the mechanism is effective for high-frequency stimulation (130 Hz) as deep brain direct stimulation, and the advantage is that the therapeutic effect for depression is high compared to other electro-therapeutic stimulation methods due to high-frequency stimulation. However, there is a disadvantage that an additional operation is required to insert the needle into the deep nuclear region of the brain.

[0008] Transcranial magnetic stimulation (tMS) is a method of non-invasively stimulating nerve cells in the brain using magnetic energy. It is effective in treating neurological and psychiatric disorders such as Parkinson's syndrome and depression. When a powerful magnetic field is generated by an induction electromagnetic coil near the head, this magnetic field passes through the skull and stimulates the nerve cells in the transcranial cortex. At this time, the activity of the cerebral cortex can be increased or decreased according to the speed of the magnetic field. For example, when the activity of the cerebral cortex is low, as in the case of depression, high-frequency stimulation can be used, and when the activity is too high, as in the case of anxiety or mania, low-frequency stimulation can be used to adjust the activity. Such tMS stimulation energy is an edge current caused by a magnetic field. The stimulation pattern is activation in the case of 10 Hz pulses (5 Hz intermittent theta burst stimulation, iTBS), and inhibition in the case of 1 Hz pulses. The mechanism is energy supply by the magnetic field and the resulting increase in gamma band power. The advantage is that it is a non-invasive stimulation and does not require an incision. However, there are limitations in that it is a large device and thus has low patient convenience, and it is difficult to perform high-frequency electrical stimulation in practice because it is a non-invasive stimulation.

[0009] In electroconvulsive therapy (ECT), the stimulation energy is alternating current (AC), the stimulation patterns are pulses and sine waves, and the mechanism is to reset nerve cells (neurons) by strong electrical stimulation (20 - 70 Hz). However, there is a problem in that anesthesia must be performed in order to apply strong electrical stimulation to reset nerve cells.

[0010] On the other hand, transcranial alternating current stimulation (tACS), which is one of the above-described electro-wave stimulation methods, is different from the other electro-wave stimulation methods. It is possible to monitor the patient's electroencephalogram (EEG) in real time through brain synchronization by current, and through this, it is possible to provide the operator with a biomarker for depression that can confirm the patient's depressive state.

[0011] That is, unlike electronic drugs based on other stimulation methods, the electronic drug for treating depression based on tACS (Transcranial Alternating Current Stimulation) can perform individualized brain stimulation according to the patient's depressive state, and thus is predicted to be effective in treating the patient's depression.

[0012] However, in order to provide an electronic drug for treating depression based on tACS, it is necessary to improve the problem of tACS that the stimulation transmission is weak due to skin impedance.

Prior Art Documents

Patent Documents

[0013] (Patent Document 1) Korean Registered Patent Publication No. 10-1465597 (registered on November 20, 2014)

[0014] (Patent Document 2) Japanese Published Patent No. 2014-502900 (published on February 6, 2014)

Summary of the Invention

Problems to be Solved by the Invention

[0015] The problem to be solved by the present invention is to provide an individualized brain stimulation device that can determine the patient's depressive state based on the patient's biological information, transmit a composite stimulation based on tACS (Transcranial Alternating Current Stimulation) to the patient's brain, and improve the patient's depressive state, enabling individualized brain stimulation.

[0016] Specifically, the present invention aims to provide a personalized brain stimulation device capable of determining a patient's depression based on at least one of the patient's biometric information, namely, heart rate variability (HRV) information, electroencephalogram (EEG) information, heart rate information, stress information, body composition information, body weight information, oxygen saturation information, pulse information, blood pressure information, iris information, voice information, vein information, and electrocardiogram (ECG) information, and transmitting a composite stimulation based on tACS (Transcranial Alternating Current Stimulation) to the patient's brain to improve the patient's depressive state.

[0017] Further, when the depression-related state of the patient is a Major Unipolar Depression (MDD) state, the present invention aims to provide a personalized brain stimulation device capable of personalized brain stimulation that can enhance gamma-level brain waves in the patient's EEG through gamma oscillation synchronization.

[0018] Further, when the depression-related state of the patient is a stress-induced depressive state, the present invention aims to provide a personalized brain stimulation device capable of personalized brain stimulation that can reduce gamma-level brain waves in the patient's EEG through synchronization of any one of delta, theta, alpha, and beta oscillations.

[0019] Further, when the depression-related state of the patient is a Bipolar Disorder (BD) state, the present invention aims to provide a personalized brain stimulation device capable of personalized brain stimulation that can enhance gamma-level brain waves when the gamma level in the patient's EEG is the lowest and reduce gamma-level brain waves when the gamma level in the patient's EEG is the highest.

[0020] However, the technical problems to be achieved by the present invention are not limited to the technical problems described above, and other technical problems not described will be clearly understood by those having ordinary knowledge in the technical field to which the present invention pertains from the following description.

Means for Solving the Problems

[0021] An individualized brain stimulation device according to an embodiment of the present invention, which is a technical means for achieving the above object, a sensor unit that measures biological information of an object; a control unit that determines whether the state of the object corresponds to a first state among a plurality of preset states related to depression based on the biological information of the object measured by the sensor unit; and a stimulation unit that transmits a stimulation corresponding to the first state determined by the control unit to the brain of the object in order to synchronize vibrations synchronized in a plurality of regions of the brain of the object, and includes the stimulation is a first stimulation for synchronizing gamma vibrations synchronized in a plurality of regions of the brain, a second stimulation for synchronizing any one of delta, theta, alpha, and beta vibrations synchronized in a plurality of regions of the brain, or a third stimulation combining the first stimulation and the second stimulation, the first, second, and third stimulations are transcranial alternating current stimulation (tACS), the transcranial alternating current stimulation is a first combined signal in which ON / OFF is repeated according to a preset first frequency, and a signal turned ON according to the first frequency is applied as a stimulation according to a preset second frequency.

[0022] In addition, the biological information can include at least one of heart rate variability (HRV) information, electroencephalogram (EEG) information, heart rate information, stress information, body composition information, body weight information, oxygen saturation information, pulse information, blood pressure information, iris information, voice information, vein information, and electrocardiogram (ECG) information.

[0023] In addition, the plurality of preset states related to depression can include a depression state due to stress, a major unipolar depression (MDD) state, and a bipolar disorder (BD) state.

[0024] In addition, when the first state of the object determined by the control unit is the major unipolar depression state, the stimulation unit transmits the first stimulation to the brain, and the transmission of the first stimulation can enhance the gamma-level brain waves in the object's brain waves through the synchronization of the gamma oscillation.

[0025] In addition, when the first state of the object determined by the control unit is a depression state due to stress, the stimulation unit transmits the second stimulation to the brain, and the transmission of the second stimulation can decrease the gamma-level brain waves in the object's brain waves through the synchronization of any one of the delta, theta, alpha, and beta oscillations.

[0026] In addition, when the first state of the object determined by the control unit is the bipolar disorder state, the stimulation unit transmits the third stimulation to the brain. When the first state of the object is the bipolar disorder state and the gamma-level brain waves in the object's brain waves are the lowest, the first stimulation is transmitted to the brain to enhance the gamma-level brain waves in the object's brain waves. When the first state of the object is the bipolar disorder state and the gamma-level brain waves in the object's brain waves are the highest, the second stimulation is transmitted to the brain to decrease the gamma-level brain waves in the object's brain waves.

[0027] Further, the electroencephalogram information is the first electroencephalogram acquired by the brain, the sensor unit measures the second electroencephalogram of the object in a state where the stimulus is transmitted to the brain, and the control unit is based on the second electroencephalogram of the object measured from the sensor unit. It is possible to determine whether or not a first reaction for synchronizing vibrations synchronized in a plurality of regions of the object's brain is derived.

[0028] Also, the first frequency is applied to induce synchronization of vibrations synchronized in a plurality of brain regions of the object, and the second frequency is applied to induce membrane action potential and brain oscillation in a plurality of brain regions of the object. It can be a value higher than the first frequency.

[0029] Further, the control unit processes the first signal due to the first complex stimulus among the signals measured by the sensor unit as noise, and the first reaction is based on the second signal excluding the first signal among the signals measured by the sensor unit. It is possible to determine whether or not it is derived.

[0030] Also, when the first reaction based on the first complex stimulus is not derived, the control unit causes the stimulation unit to output at least one of the output, waveform, and period of the stimulation based on the first frequency, the second frequency, and the second frequency. The stimulation unit can be controlled to transmit a modified second complex stimulus to the brain of the object.

[0031] Further, the first reaction relates to synchronization of any one of gamma oscillation, delta oscillation, theta oscillation, alpha oscillation, and beta oscillation synchronized in a plurality of regions of the brain, and the first frequency is a frequency of 30 Hz to 80 Hz for synchronizing gamma oscillation synchronized in a plurality of brain regions of the object including the prefrontal cortex (PFC) and hippocampus of the object, a frequency of 14 Hz to 29 Hz for synchronizing the beta oscillation, a frequency of 8 Hz to 13 Hz for synchronizing the alpha oscillation, a frequency of 4 Hz to 7 Hz for synchronizing the theta oscillation, or a frequency exceeding 0 Hz and less than 4 Hz for synchronizing the delta oscillation.

[0032] Also, based on the fact that the magnitude of the first signal has a difference greater than or equal to a preset value from the magnitude of the second signal, it is possible to provide an individualized brain stimulation device characterized in that signal interference by the first complex stimulus is negligible.

Advantages of the Invention

[0033] According to an embodiment of the present invention, it is possible to provide an individualized brain stimulation device capable of individualized brain stimulation that determines the depressive state of a patient based on the patient's biological information and transmits a composite stimulus based on tACS (Transcranial Alternating Current Stimulation) to the patient's brain to improve the patient's depressive state.

[0034] Specifically, the present invention can determine a patient's depression based on at least one of the patient's biometric information, namely, heart rate variability (HRV) information, electroencephalogram (EEG) information, heart rate information, stress information, body composition information, body weight information, oxygen saturation information, pulse information, blood pressure information, iris information, voice information, vein information, and electrocardiogram (ECG) information, and can provide a personalized brain stimulation device capable of transmitting a composite stimulation based on transcranial alternating current stimulation (tACS) to the patient's brain to improve the patient's depressive state.

[0035] Further, when the patient's depression-related state is a major unipolar depression (MDD) state, the present invention can provide a personalized brain stimulation device capable of personalized brain stimulation that can enhance gamma-level brain waves in the patient's electroencephalogram through gamma oscillation synchronization.

[0036] Further, when the patient's depression-related state is a stress-induced depressive state, the present invention can provide a personalized brain stimulation device capable of personalized brain stimulation that can reduce gamma-level brain waves in the patient's electroencephalogram through synchronization of any of the vibrations of delta, theta, alpha, and beta.

[0037] Further, when the patient's depression-related state is a bipolar disorder (BD) state, the present invention can provide a personalized brain stimulation device capable of personalized brain stimulation that can enhance gamma-level brain waves when the gamma level in the patient's electroencephalogram is the lowest and reduce gamma-level brain waves when the gamma-level brain waves in the patient's electroencephalogram are the highest.

[0038] However, the effects obtained by the present invention are not limited to the effects described above, and other effects not described will be clearly understood by those with ordinary knowledge in the technical field to which the present invention belongs from the following description.

Brief Description of the Drawings

[0039]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Modes for Carrying Out the Invention

[0040] Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings so that those having ordinary knowledge in the technical field to which the present invention belongs can easily implement them. However, since the description of the present invention is only an example for structural or functional explanation, the scope of the rights of the present invention should not be construed as being limited by the embodiments described in the text. That is, the embodiments can be variously changed and can have various forms, so the scope of the rights of the present invention should be understood to include equivalents that can realize the technical idea. In addition, the objects and effects shown in the present invention do not mean that a specific embodiment must include all of them, nor do they mean that only the effects need to be included, so the scope of the rights of the present invention should not be understood to be limited thereby.

[0041] The meanings of the terms described in the present invention should be understood as follows.

[0042] Terms such as "first" and "second" are used to distinguish one component from another, and the scope of rights is not limited by these terms. For example, the first component can be named the second component, and similarly, the second component can be named the first component. When a component is described as "connected to" another component, it should be understood that it may be directly connected to the other component, but there may also be other components in between. Conversely, when a component is described as "directly connected to" another component, it should be understood that there are no other components in between. Also, other expressions for describing the relationship between components, such as "between", "directly between", or "adjacent to" and "directly adjacent to", should be interpreted in the same way.

[0043] Singular expressions should be understood to include plural expressions unless the context clearly has a different meaning, and terms such as "including" or "having" are used to specify the presence of the described features, numerical values, steps, operations, components, parts, or combinations thereof, and should not be construed as precluding the presence or possibility of addition of one or more other features, numerical values, steps, operations, components, parts, or combinations thereof.

[0044] All terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which the present invention pertains, unless otherwise specifically defined. Terms defined in commonly used dictionaries should be interpreted as consistent with the meaning in the context of the related art, and should not be interpreted as having an ideal or overly formal meaning unless specifically defined in the present invention.

[0045] Configuration of the brain stimulation system

[0046] Hereinafter, the configuration of the preferred embodiment will be described in detail with reference to the accompanying drawings.

[0047] FIG. 1 is a block configuration diagram of a brain stimulation system according to an embodiment of the present invention.

[0048] Referring to FIG. 1, the brain stimulation system (1) can include a brain stimulation device (100) and a server (200).

[0049] First, the brain stimulation device (100) can include a wireless communication unit (110), an A / V (Audio / Video) input unit (120), a user input unit (130), a sensing unit (140), an output unit (150), a memory (160), an interface unit (170), a control unit (180), a power supply unit (190), and a stimulation unit (300), etc.

[0050] However, the components shown in FIG. 1 are not necessarily essential, and a brain stimulation system (1) having more components or fewer components than those may also be realized.

[0051] Hereinafter, the above components will be sequentially described.

[0052] The wireless communication unit (110) can include one or more modules that enable wireless communication between the brain stimulation system (1) and a wireless communication system, or between devices located on a network.

[0053] For example, the wireless communication unit (110) can include a mobile communication module (112), a wireless Internet module (113), a short-range communication module (114), and a location information module (115), etc.

[0054] The broadcast receiving module (111) receives broadcast signals and / or broadcast-related information from an external broadcast management server through a broadcast channel.

[0055] The broadcast channel can include a satellite channel and a terrestrial wave channel. The broadcast management server means a server that generates and transmits a broadcast signal and / or broadcast-related information, or a server that provides the already generated broadcast signal and / or broadcast-related information and transmits it to the brain stimulation device (100). The broadcast signal can include not only a TV broadcast signal, a radio broadcast signal, and a data broadcast signal, but also a broadcast signal in a form in which a data broadcast signal is combined with a TV broadcast signal or a radio broadcast signal.

[0056] The broadcast-related information can mean information related to a broadcast channel, a broadcast program, or a broadcast service provider.

[0057] The broadcast-related information can also be provided through a mobile communication network. In this case, it can be received by the mobile communication module (112).

[0058] The broadcast-related information can exist in various forms. For example, it can exist in the form of an EPG (Electronic Program Guide) of DMB (Digital Multimedia Broadcasting) or an ESG (Electronic Service Guide) of DVB-H (Digital Video Broadcast-Handheld).

[0059] The broadcast receiving module (111) can receive digital broadcast signals using, for example, digital broadcast systems such as DMB-T (Digital Multimedia Broadcasting-Terrestrial), DMB-S (Digital Multimedia Broadcasting-Satellite), MediaFLO (Media Forward Link Only), DVB-H (Digital Video Broadcast-Handheld), DVB-CBMS, OMA-BCAST, ISDB-T (Integrated Services Digital Broadcast-Terrestrial). Of course, the broadcast receiving module (111) can be configured to be compatible not only with the above digital broadcast systems but also with other broadcast systems.

[0060] The broadcast signals and / or broadcast-related information received through the broadcast receiving module (111) can be stored in the memory (160).

[0061] The mobile communication module (112) transmits and receives radio signals with at least one of a base station, an external brain stimulation device (100), and a server over a mobile communication network. The radio signals can include voice call signals, video call signals, or various forms of data associated with text / multimedia message transmission and reception.

[0062] The wireless Internet module (113) means a module for wireless Internet connection and can be built into or externally attached to the brain stimulation device (100).

[0063] As the wireless Internet technology, WLAN (Wireless LAN) (Wi-Fi), Wibro (Wireless Broadband), Wimax (World Interoperability for Microwave Access), HSDPA (High Speed Downlink Packet Access), etc. can be used.

[0064] The short-range communication module (114) means a module for short-range communication. As the technology of the short range communication, Bluetooth, RFID (Radio Frequency Identification), IrDA (Infrared Data Association), UWB (Ultra-Wideband), ZigBee, etc. can be used.

[0065] The position information module (115) is a module for acquiring the position of the brain stimulation device (100), and a typical example thereof is a GPS (Global Position System) module. In the current technology, the GPS module (115) calculates distance information from three or more satellites and accurate time information, and then accurately calculates three-dimensional current position information based on latitude, longitude, and altitude by applying trigonometry to the calculated information. Currently, a method of calculating position and time information using three satellites and further using one satellite to correct errors in the calculated position and time information is widely used. Also, the GPS module (115) can calculate speed information by continuously calculating the current position in real time.

[0066] Referring to FIG. 1, the A / V (Audio / Video) input unit (120) is for input of an audio signal or a video signal, and this may include a camera (121) and a microphone (122), etc.

[0067] The camera (121) processes an image frame such as a still image or a moving image obtained by an image sensor in a shooting mode, and the processed image frame can be displayed on the display unit (151).

[0068] The image frame processed by the camera (121) can be stored in the memory (160) or transmitted externally through the wireless communication unit (110).

[0069] The camera (121) may be provided with two or more depending on the usage environment.

[0070] The microphone (122) inputs an external acoustic signal by a microphone in a recording mode, a voice recognition mode, etc., and processes it into electrical voice data.

[0071] The processed voice data can be converted into a form that can be transmitted to a mobile communication base station through the mobile communication module (112) and output.

[0072] Various noise removal algorithms for removing noise generated in the process of inputting an external acoustic signal can be implemented in the microphone (122).

[0073] Next, the user input unit (130) generates input data for the user to control the operation of the brain stimulation system (1).

[0074] The user input unit (130) can be composed of a key pad, a dome switch, a touch pad (static pressure / electrostatic), a jog wheel, a jog switch, etc.

[0075] The sensing unit (140) senses the current state of the brain stimulation system (1), such as the open / closed state of the brain stimulation system (1) main body, the position of the brain stimulation system (1), the presence or absence of user contact, the orientation of the brain stimulation system (1), the acceleration / deceleration of the brain stimulation system (1), etc., and generates a sensing signal for controlling the operation of the brain stimulation system (1).

[0076] The sensing unit (140) can also sense the presence or absence of power supply from the power supply unit (190), the presence or absence of connection of an external device to the interface unit (170), etc.

[0077] In particular, the sensing unit (140) according to the present invention can include an EGG sensor (141) and a biological information sensor (142) for measuring biological information of a subject (patient).

[0078] In the present invention, the biological information of the subject is not limited, but can include at least one of heart rate variability (HRV) information, electroencephalogram (EEG) information, heart rate information, stress information, body composition information, weight information, oxygen saturation information, pulse information, blood pressure information, iris information, voice information, vein information, and electrocardiogram (ECG) information.

[0079] Also, the EGG sensor (141) means a sensor for measuring the electroencephalogram information of the subject, and the biological information sensor (142) can be a sensor for measuring other biological information excluding the electroencephalogram information measurable by the EGG sensor (141).

[0080] That is, it is desirable that the sensing unit (140) be understood as a sensor for measuring the above-described biological information.

[0081] Brain waves are generated by communication between nerve cells in the brain, which is responsible for an individual's thoughts, emotions, and actions. Brain waves are synchronous electrical waves generated by the transmission of signals between nerve cells in the cerebral cortex. Brain waves can be measured by an electroencephalogram (EEG) examination that measures the potential difference between surface electrodes located in specific regions of the scalp. The brain waves shown by the electroencephalogram are the sum of the electrical activities of a large number of cerebral cortex nerve cells under the surface electrodes.

[0082] Brain waves appear in various frequency bands, and these frequency bands indicate the state of the brain. Brain waves are classified into delta waves, theta waves, alpha waves, beta waves, gamma waves, etc. according to the frequency band.

[0083] Delta waves have a frequency band of less than 4 Hz and large amplitudes. They are waveforms that appear in a deep sleep state without dreaming.

[0084] Theta waves are brain waves in the 4 - 7 Hz range, which occur in specific sleep states and also appear during deep meditation. They are also known to be involved in the process of fixing memories through learning during sleep.

[0085] Alpha waves are around 8 - 13 Hz and are brain waves that appear in a waking state of quiet rest.

[0086] Beta waves are in the 14 - 29 Hz range and are the rhythm of the activated cerebral cortex. They are waveforms that appear when the cerebral cortex performs general cognitive thinking activities in a waking state.

[0087] Gamma waves are waveforms in the 30 - 80 Hz range and are high - frequency brain waves that appear in a state of tension or excitement. They are known as waveforms that appear in a state of high concentration.

[0088] Electroencephalogram (EEG) is a non - invasive technique for measuring brain waves. It uses conductive paste to fix planar electrodes on the scalp and measures the potential difference between two electrodes.

[0089] Multiple electrodes are attached to standard positions on the scalp, and the weak - amplitude voltage changes generated from nerve cells in the cerebral cortex are amplified through a signal amplifier and recorded by a brain wave recording device.

[0090] Brain waves appear as a result of synaptic currents in dendrites, which are electric currents generated during the process of communication between nerve cells in the cerebral cortex located just below the skull.

[0091] The synaptic current of a single nerve cell is extremely weak, and in order for its signal to reach the electrodes attached to the scalp, it must pass through multiple meninges, cerebrospinal fluid, skull, and scalp layers. The reason why electroencephalogram (EEG) can be electrically recorded is that EEG is the sum of signals generated when thousands of nerve cells are simultaneously activated. Therefore, the more synchronized the activities of nerve cells are, the more they appear as brain waves in the form of low-frequency waveforms with large amplitudes.

[0092] On the other hand, the output unit (150) is for generating outputs related to vision, audition, or touch, etc., and this can include a display unit (151), an acoustic output module (152), an alarm unit (153), a haptic module (154), a projector module (155), a head-up display (HUD), a head-mounted display (HMD), etc.

[0093] The display unit (151) displays (outputs) the information processed by the brain stimulation system (1).

[0094] The display unit (151) can include at least one of a liquid crystal display (LCD), a thin film transistor-liquid crystal display (TFT LCD), an organic light-emitting diode (OLED), a flexible display, and a 3D display.

[0095] Among these, it can be configured as a transparent type or a light-transmissive type that allows viewing the outside. This may be referred to as a transparent display, and typical examples of the transparent display include TOLED (Transparent OLED). The rear structure of the display unit (151) can also be configured as a light-transmissive structure. With such a structure, the user can see an object located behind the body of the brain stimulation system (1) through the area occupied by the display unit (151) of the body of the brain stimulation system (1).

[0096] Depending on the embodiment of the brain stimulation system (1), there can be two or more display units (151). For example, in the brain stimulation system (1), a plurality of display units can be arranged separately or integrally on one surface, or can be arranged on different surfaces respectively.

[0097] When the display unit (151) and a sensor that senses a touch operation (hereinafter referred to as a "touch sensor") form an interlayer structure (hereinafter referred to as a "touch screen"), the display unit (151) can be used not only as an output device but also as an input device. The touch sensor can have forms such as a touch film, a touch sheet, a touch pad, etc.

[0098] The touch sensor can be configured to convert changes such as pressure applied to a specific part of the display unit (151) or capacitance generated at a specific part of the display unit (151) into an electrical input signal. The touch sensor can be configured to detect not only the touched position and area but also the pressure at the time of touch.

[0099] When there is a touch input to the touch sensor, the corresponding signal is sent to the touch controller. The touch controller processes the signal and transmits the corresponding data to the control unit (180). Thereby, the control unit (180) can know which area of the display unit (151) has been touched.

[0100] The proximity sensor can be disposed in the internal area of the brain stimulation system (1) surrounded by the touch screen or near the touch screen. The proximity sensor refers to a sensor that detects the presence or absence of an object approaching a predetermined detection surface or an object existing in the vicinity without mechanical contact by using the force of an electromagnetic field or infrared rays. The proximity sensor has a longer lifespan and higher utilization rate than a contact sensor.

[0101] Examples of the proximity sensor include a transmissive photoelectric sensor, a direct reflection photoelectric sensor, a mirror reflection photoelectric sensor, a high-frequency oscillation proximity sensor, a capacitance proximity sensor, a magnetic proximity sensor, an infrared proximity sensor, etc. When the touch screen is a capacitive type, it is configured to detect the proximity of the pointer based on the change in the electric field due to the proximity of the pointer. In this case, the touch screen (touch sensor) may also be classified as a proximity sensor.

[0102] The proximity sensor senses proximity touches and proximity touch patterns (for example, proximity touch distance, proximity touch direction, proximity touch speed, proximity touch time, proximity touch position, proximity touch movement state, etc.). Information corresponding to the sensed proximity touch operations and proximity touch patterns can be output on the touch screen.

[0103] The acoustic output module (152) can output audio data received from the wireless communication unit (110) in a recording mode, a voice recognition mode, a broadcast reception mode, etc., or stored in the memory (160).

[0104] The acoustic output module (152) may also output an acoustic signal related to the function executed in the brain stimulation system (1). Such an acoustic output module (152) includes a receiver, a speaker, a buzzer, etc.

[0105] The alarm unit (153) outputs a signal for notifying the occurrence of an event in the brain stimulation system (1).

[0106] The alarm unit (153) can also output a signal for notifying the occurrence of an event in other forms than video signals and audio signals, for example, vibration.

[0107] The video signal and the audio signal can also be output through the display unit (151) and the acoustic output module (152), and they (151, 152) may be classified as part of the alarm unit (153).

[0108] The haptic module (154) generates various tactile effects that can be felt by the user. A typical example of the tactile effect generated by the haptic module (154) is vibration. The intensity and pattern of the vibration generated by the haptic module (154) are controllable.

[0109] For example, different vibrations can be synthesized and output, or output sequentially.

[0110] In addition to vibration, the haptic module (154) can generate various tactile effects such as the effect of a pin array that moves vertically with respect to the contact skin surface, the injection force and suction force of air through injection ports and suction ports, rubbing against the skin surface, the contact of electrodes, the effect of electrostatic force, and the effect of reproducing cold and warm sensations using elements capable of heat absorption and heat generation.

[0111] The haptic module (154) can not only transmit the tactile effect through direct contact, but can also be implemented so that the user can feel the tactile effect through the muscle sense of fingers, arms, etc. The haptic module (154) may be provided with two or more depending on the embodiment of the brain stimulation system (1).

[0112] The projector module (155) can display on an external screen or wall a video that is the same as or at least partially different from the video displayed on the display unit (151) according to the control signal of the control unit (180) as a component for executing an image projection function using the brain stimulation system (1).

[0113] Specifically, the projector module (155) can include a light source (not shown) that generates light (e.g., laser light) for outputting a video externally, video generation means (not shown) for generating a video to be output externally using the light generated by the light source, and a lens (not shown) for magnifying and outputting the video externally at a fixed focal length. Further, the projector module (155) can include a device (not shown) that can mechanically move the lens or the entire module to adjust the video projection direction.

[0114] The projector module (155) can be classified into a CRT (Cathode Ray Tube) module, an LCD (Liquid Crystal Display) module, a DLP (Digital Light Processing) module, etc. according to the element type of the display means. In particular, the DLP module is advantageous for miniaturization of the projector module (151) in a method of magnifying and projecting a video generated by reflecting light generated from a light source onto a DMD (Digital Micromirror Device) chip.

[0115] Desirably, the projector module (155) can be provided vertically on the side, front, or back of the brain stimulation system (1). Of course, it goes without saying that the projector module (155) can be provided at any position of the brain stimulation system (1) as needed.

[0116] In addition, a head-up display (HUD, 156) refers to a device that projects information such as the current speed of a vehicle, remaining fuel level, and navigation guidance information as graphic images onto the windshield in front of the driver in a vehicle or the like.

[0117] Also, a head-mounted display (HMD, 157) is a typical device that can output virtual reality (VR) information.

[0118] Virtual reality (VR) generally refers to a human-computer interface that creates a specific environment or situation as three-dimensional (3D) content with a sense of depth through a computer, and enables the user to interact with the 3D content as if they were interacting with the actual surrounding situation or environment.

[0119] Generally, the sense of depth perceived by humans is caused by the combined action of factors such as the degree of change in the thickness of the lens depending on the position of the observed object, the angular difference between both eyes and the object, the differences in the position and shape of the object seen by the left and right eyes, the parallax caused by the movement of the object, and other various psychological and memory effects.

[0120] Among these, the most important factor for humans to feel a sense of depth is binocular disparity, which is caused by the fact that the two eyes of a person are separated horizontally by about 65 cm. That is, due to binocular disparity, the angles of view with respect to the object are different, and the images entering each eye have different images. When these two images are transmitted to the brain through the retina, the brain can accurately fuse these two pieces of information and recognize it as the original 3D stereoscopic image.

[0121] Such 3D content with a sense of depth has already been widely used in various media fields and has received favorable reviews from consumers. For example, 3D movies, 3D games, and immersive displays are typical examples.

[0122] With the spread of virtual reality technology and 3D content like this, the development of technologies that can provide more immersive virtual reality services is being demanded from various angles.

[0123] Generally, an image display device refers to an image display device that forms a focus using a precision optical device so that virtual large screens are configured at a distance for the video light generated at a position very close to the eyes, allowing the user to see an enlarged virtual image.

[0124] In addition, the image display device can be divided into a sealed type (See-close) where the surrounding environment cannot be seen and only the video light emitted from the display element can be seen, and a transmissive type (See-through) where the surrounding environment can be seen through a window and at the same time the video light emitted from the display element can be seen.

[0125] The head-mounted display (HMD, 157) according to the present invention refers to various digital devices that are worn on the head like glasses and can provide multimedia content. Due to the trend of weight reduction and miniaturization of digital devices, various wearable computers have been developed, and HMDs are also widely used.

[0126] The HMD (157) can provide various conveniences to the user by combining with augmented reality technology, N-screen technology, etc., exceeding just a simple display function.

[0127] For example, when a microphone and a speaker are attached to the HMD (157), the user can make a phone call while wearing the HMD (157). Also, for example, when an infrared camera (122) is attached to the HMD (157), the user can capture an image in the direction the user desires while wearing the HMD (157).

[0128] In addition, the memory unit (160) may store a program for the processing and control of the control unit (180), and can also function to temporarily store input / output data (for example, messages, audio, still images, moving images, etc.). The usage frequency for each of the data can also be stored together in the memory unit (160). Further, the memory unit (160) can store data related to various patterns of vibration and sound output when a touch input is made on the touch screen.

[0129] The memory (160) can include at least one type of storage medium such as a flash memory type, a hard disk type, a multimedia card micro type, a card type memory (for example, SD or XD memory, etc.), a RAM (Random Access Memory), an SRAM (Static Random Access Memory), a ROM (Read-Only Memory), an EEPROM (Electrically Erasable Programmable Read-Only Memory), a PROM (Programmable Read-Only Memory), a magnetic memory, a magnetic disk, and an optical disk. The brain stimulation system (1) can also operate in association with a web storage that performs the storage function of the memory (160) on the internet.

[0130] The interface unit (170) serves as a passageway to all external devices connected to the brain stimulation system (1). The interface unit (170) receives data from external devices, supplies power, and transmits it to each component inside the brain stimulation system (1), or enables the data inside the brain stimulation system (1) to be transmitted to external devices. For example, it can include a wired / wireless headset port, an external charger port, a wired / wireless data port, a memory card port, a port for connecting a device equipped with an identification module, an audio I / O (Input / Output) port, a video I / O (Input / Output) port, an earphone port, etc.

[0131] The identification module is a chip that stores various information for authenticating the usage rights of the brain stimulation system (1), and can include a user identification module (User Identify Module, UIM), a subscriber identification module (Subscriber Identify Module, SIM), a universal subscriber identity module (Universal Subscriber Identity Module, USIM), etc. The device equipped with the identification module (hereinafter referred to as the "identification device") can be manufactured in the form of a smart card. Therefore, the identification device can be connected to the brain stimulation system (1) through a port.

[0132] When the brain stimulation system (1) is connected to an external cradle, the interface unit can become a passageway for power from the cradle to be supplied to the brain stimulation system (1), or a passageway for various command signals input by the user from the cradle to be transmitted to the mobile device. The various command signals or the power input from the cradle can also act as signals for recognizing that the mobile device is correctly mounted on the cradle.

[0133] The control unit (controller, 180) generally controls the overall operation of the brain stimulation system (1).

[0134] In the present invention, the control unit (180) can be provided in the brain stimulation device (100), but is not limited thereto, and preferably can be implemented as an existing (or installed) application in a device (such as a smartphone, tablet, PC, etc.) equipped by the user of the brain stimulation device (100).

[0135] The power supply unit (190) supplies power required for the operation of each component by applying an external power supply or an internal power supply under the control of the control unit (180).

[0136] The various embodiments described herein can be implemented in a computer or similar device-readable recording medium using, for example, software, hardware, or a combination thereof.

[0137] According to a hardware implementation, the embodiments described herein can be implemented using at least one of ASICs (application specific integrated circuits), DSPs (digital signal processors), DSPDs (digital signal processing devices), PLDs (programmable logic devices), FPGAs (field programmable gate arrays), processors, controllers, micro-controllers, microprocessors, and other electrical units for performing other functions. In some cases, the embodiments described herein can be implemented as the control unit (180) itself.

[0138] According to a software implementation, examples such as the procedures and functions described in this specification can be implemented as separate software modules. Each of the software modules can execute one or more functions and operations described in this specification. The software code can be implemented as a software application written in an appropriate programming language. The software code can be stored in a memory (160) and executed by a control unit (180).

[0139] In addition, the stimulation unit (300) provides a function of stimulating the user's brain through neuromodulation techniques, neurofeedback techniques, sensory stimulation techniques, and the like.

[0140] The stimulation unit (300) according to the present invention can be provided in a brain stimulation device (100) and can include an electrical stimulation unit (310), a magnetic stimulation unit (320), an ultrasonic stimulation unit (330), an optical stimulation unit (340), and a sensory stimulation unit (350).

[0141] First, the electrical stimulation unit (310) can include a DBS stimulation unit (311), a tDCS stimulation unit (312), and a tACS stimulation unit (313).

[0142] The DBS stimulation unit (311) utilizes deep brain stimulation (DBS), positions fine electrodes at deep nuclear sites in the brain, and stimulates the activity of nerve cells.

[0143] DBS stimulation can be provided in DC format, Pulse format, or NIR format.

[0144] Regarding deep brain stimulation (DBS), when electrical stimulation is administered to the nuclei of specific brain regions, it is possible to treat and improve symptoms of various diseases including movement disorders by interfering with pathological signals generated in the brain region.

[0145] Deep brain stimulation places fine electrodes in deep nuclear regions of the brain and supplies the necessary power for activity from a pulse generator inserted in the chest in a manner similar to a cardiac pacemaker.

[0146] This can block depolarization block, that is, the neural output of nerve cells located at the electrode site.

[0147] Also, synaptic inhibition, that is, it can indirectly regulate the output of nerve cells by activating axon terminals with synaptic connections to nerve cells near the electrode.

[0148] Next, the tDCS stimulation unit (312) uses transcranial direct current stimulation, which stimulates nerve cells in the cerebral cortex with a weak direct current form by attaching electrodes to the head.

[0149] The tDCS stimulation unit (312) is one method of non-invasive brain stimulation aimed at the recovery of sequelae due to brain injury, and can help improve brain function by adjusting the active state of the cranial nerves through electrical stimulation.

[0150] The tACS (transcranial Alternating Current Stimulation) stimulation unit (313) attaches electrodes and transmits a fine current of less than 1 mA through them to the skull, and is used for non-drug treatments that improve symptoms such as anxiety, depression, insomnia, stress, headache, and various types of pain.

[0151] tACS (transcranial Alternating Current Stimulation) stimulation is effective in regulating microglial cells, is safe using a fine current, has no side effects, and allows for medium- to long-term treatment.

[0152] Also, it is a state-of-the-art treatment method highly compatible with existing chemotherapy that promotes and / or suppresses hormone secretion.

[0153] When applying tACS (transcranial Alternating Current Stimulation), it is possible to induce sleep and improve sleep quality by maintaining the stable DMN of the brain itself.

[0154] Also, it is possible to induce sleep and improve sleep quality by improving hormones (such as serotonin, melatonin, GABA, etc.).

[0155] Also, the brain tissue can be stimulated to restore the neurochemical substances to the balance before stress.

[0156] The magnetic stimulation unit (320) uses the TMS (transcranial magnetic stimulation) method, which is called transcranial magnetic stimulation, and non-invasively stimulates nerve cells in the brain using magnetic energy.

[0157] This is effective for the treatment of neurological and mental diseases such as Parkinson's syndrome and depression.

[0158] When a powerful magnetic field is generated by an induction electromagnetic coil near the head, this magnetic field stimulates the nerve cells of the transcranial cortex while passing through the skull.

[0159] At this time, the activity of the cerebral cortex can be increased or decreased according to the speed of the magnetic field. For example, when the activity of the cerebral cortex is low, such as in depression, high-frequency stimulation is used, and when the activity is too high, such as in anxiety disorder or mania, low-frequency stimulation is used to adjust the activity.

[0160] Also, the ultrasonic stimulation unit (330) utilizes ultrasonic waves for therapeutic effects and is widely used in obstetrics and gynecology, orthopedics, dermatology, etc.

[0161] Ultrasound refers to sound waves with frequencies beyond the limit that humans can hear. Generally, the sound waves that a healthy person can hear are 20 kHz, and ultrasound refers to sound waves beyond this frequency. Ultrasound therapy utilizes such ultrasound for therapeutic effects and is widely used in obstetrics and gynecology, orthopedics, dermatology, etc.

[0162] Ultrasound therapy can be broadly divided into high-intensity ultrasound above 1000 W / cm2 and low-intensity ultrasound in the range of 10 - 50 W / cm2. High-intensity ultrasound therapy is a method of selectively heating tissues for treatment and is mainly used for tumor treatment. Low-intensity ultrasound therapy heats subcutaneous tissues for treatment and is used in orthopedic treatments such as skin lifting, fracture, and chondrocyte regeneration. And ultrasound therapy has the advantages of no skin damage and fast recovery.

[0163] HIFU (High Intensity Focused Ultrasound) is a method that utilizes the heat and energy generated when ultrasonic beams transmitted from multiple directions are focused to necrotize tumors or reduce their size without incision or surgery. This is used in the treatment of uterine fibroids, prostate cancer, bone metastasis cancer, liver cancer, etc.

[0164] LIFU (Low Intensity Focused Ultrasound) is a method that can obtain a skin lifting effect through necrosis of subcutaneous tissues by utilizing heat. Although the treatment mechanism is similar to that of high-intensity focused ultrasound, there are differences in the intensity and range used.

[0165] LIPUS (Low Intensity Pulsed Ultrasound) is a method of radiating ultrasound to the treatment site to stimulate physical vibration and activate cells, and is used in fracture treatment, chondrocyte regeneration treatment, etc.

[0166] Sonophoresis is used for the purpose of transmitting drugs through the skin using low-frequency ultrasound.

[0167] In addition, the light stimulation unit (340) can apply the Brain Photo Modulation method in a manner of irradiating the head with light to stimulate the brain.

[0168] According to the light stimulation unit (340), light with a wavelength of 600 - 1000 nm penetrates the cell wall and participates in the COX (Cytochrome c oxidase) respiratory chain in the mitochondria.

[0169] As a result, it is possible to increase synaptogenesis / angiogenesis / blood flow / prevent inflammation / prevent cell apoptosis / increase SOD / decrease neuroexcitotoxicity.

[0170] In addition, the sensory stimulation unit (350) can include a visual stimulation unit (351) and an auditory stimulation unit (352).

[0171] The sensory stimulation unit (350) is a method of indirectly stimulating the brain by stimulating other organs without directly stimulating the brain.

[0172] The visual stimulation unit (351) means radiation that can enter the naked eye and cause a sense of light.

[0173] For example, the visual stimulation unit (351) usually uses a white stroboscope flash of about 100,000 lux, fixes the stroboscope bulb about 20 cm in front of the eyes of the subject in a closed - eye state, and irradiates the entire visual field. As a stimulation method, stimulation is applied for 10 seconds in order from low frequency to high frequency, and then the brain waves and the state of the subject are observed for the next 10 seconds, and then the next stimulation is carried out.

[0174] On the other hand, the server (200) can build a database and exchange information with the brain stimulation device (100).

[0175] At this time, short - range communication or long - range communication can be applied between the server (200) and the brain stimulation device (100).

[0176] In addition, the server (200) can form a network with a medical institution, receive information regarding the judgment and opinions of medical staff, and transmit it to the brain stimulation device (100).

[0177] Structure of the brain stimulation device

[0178] FIG. 2 is a drawing showing an example of the brain stimulation device.

[0179] Referring to FIG. 2, the brain stimulation device (100) can be manufactured in a form that can be worn on the head so as to be able to apply stimulation to the brain of a subject (patient) as shown in FIG. 3.

[0180] At this time, a plurality of sensing units (140) can be arranged in the brain stimulation device (100) to measure the biological information of the subject.

[0181] In one embodiment, the brain stimulation device (100) can be implemented as an EEG sensor (141) for measuring the electroencephalogram (EEG) information of the subject, which is one of the biological information of the subject, for each of the plurality of sensing units (140).

[0182] In addition, the EEG information measured by the EEG sensor (141) is the first EEG acquired by the EEG sensor (141) from the subject's brain before the stimulation unit (300) transmits stimulation to the subject's brain. The EEG sensor (141) can measure not only the first EEG but also the second EEG of the subject in a state where the stimulation unit (300) transmits stimulation to the subject's brain.

[0183] And the sensing unit (140) can be implemented as a biological information sensor (142) for measuring the biological information of the subject excluding the EEG information. In one embodiment, the description will be made based on the EEG sensor (141).

[0184] In addition, a plurality of electrical stimulation units (310) can be arranged in the brain stimulation device (100) to transmit stimulation for improving the subject's depression to the subject's brain.

[0185] The plurality of electrical stimulation units (310) can be tACS stimulation units (313) for transmitting tACS-based composite stimulation to the target brain.

[0186] Also, although not shown in the drawings, the plurality of electrical stimulation units (310) can include a DBS stimulation unit (311) and a tDCS stimulation unit (312), or can be replaced by at least one of the DBS stimulation unit (311) and the tDCS stimulation unit (312).

[0187] The method of transmitting stimulation to the target brain through such a brain stimulation device (100) is as follows.

[0188] Stimulation method related to the present invention

[0189] First, the sensing unit (140) can measure the biological information of the target (patient).

[0190] Based on the biological information of the target measured by the sensing unit (140), the control unit (180) can determine that the state of the target corresponds to the first state among a plurality of preset states related to depression shown in FIG. 3.

[0191] FIG. 3 is a drawing for explaining a plurality of preset states related to depression.

[0192] In the present invention, the plurality of preset states related to depression can include a stress-induced depression state (stress depression), a major unipolar depression (MDD) state, and a bipolar disorder (BD) state as shown in FIG. 3.

[0193] On the other hand, the electrical stimulation unit (310) can transmit different stimulations to the target brain according to the first state of the target determined by the control unit (180) in order to adjust the synchronized oscillations in a plurality of regions of the target brain.

[0194] In the present invention, the stimulus transmitted to the target brain can be a first stimulus for adjusting gamma oscillations synchronized in a plurality of regions of the brain, a second stimulus for adjusting any of delta, theta, alpha, and beta oscillations synchronized in a plurality of regions of the brain, or a third stimulus combining the first stimulus and the second stimulus.

[0195] The first stimulus, the second stimulus, and the third stimulus can each be transcranial alternating current stimulation (tACS, 400) transmitted from the electrical stimulation unit (310) to the target brain.

[0196] That is, it is desirable that the electrical stimulation unit (310) is composed of a tACS stimulation unit (313) capable of transmitting a tACS stimulation (400) to the target brain.

[0197] When the first state of the target determined by the control unit (180) is the major depressive state, the tACS stimulation unit (313) can transmit the first stimulus to the target brain.

[0198] At this time, the transmission of the first stimulus is for enhancing gamma-level brain waves in the target brain waves through the adjustment of gamma oscillations as shown in FIG. 3.

[0199] When the first state of the target determined by the control unit (180) is the stress-induced depressive state, the tACS stimulation unit (313) can transmit the second stimulus to the target brain.

[0200] At this time, the transmission of the second stimulus is for reducing gamma-level brain waves in the target brain waves through the adjustment of any of delta, theta, alpha, and beta oscillations as shown in FIG. 3.

[0201] When the first state of the target determined by the control unit (180) is the bipolar disorder (BD) state, the tACS stimulation unit (313) can transmit the third stimulus to the target brain.

[0202] More specifically, when the first state of the subject is a bipolar disorder state and the gamma-level brain wave in the subject's brain wave is the lowest, the tACS stimulation unit (313) can transmit a first stimulation to the subject's brain to enhance the gamma-level brain wave in the subject's brain wave.

[0203] Conversely, when the first state of the subject is a bipolar disorder state and the gamma-level brain wave in the subject's brain wave is the highest, the tACS stimulation unit (313) can transmit a second stimulation to the subject's brain to reduce the gamma-level brain wave in the subject's brain wave.

[0204] The tACS stimulation method proposed by the present invention

[0205] Inducing the entrainment of synchronized gamma oscillations by the tACS stimulation proposed by the present invention and sensing this in real time has been impossible in the past.

[0206] That is, for the GET (Gamma Entrainment Therapy) method, a technology for monitoring brain signals in real time is essential. However, gamma oscillation is in the region of about 25 - 100 Hz, usually 40 Hz is the target frequency, and for the method of oscillating at 40 Hz, since the oscillation frequency and the frequency to be measured by EEG are in the same frequency region, real-time monitoring is technically impossible.

[0207] For example, when a 40 Hz stimulation is given to synchronize gamma oscillations, since the sensing by EEG also targets signals in the 40 Hz band, there is a major problem that it is impossible to distinguish whether the measured signal is noise from the stimulation or the target EEG signal. Therefore, the method proposed by the present invention could not be realized in the past.

[0208] In contrast, in the present invention, as a tACS stimulation method for real-time EEG signal acquisition, a composite stimulation method of Burst Frequency (Burst) and Pulse Repetition Frequency (PRF) can be used to separate the EEG frequency and the stimulation frequency band.

[0209] Also, the frequency of the composite stimulation follows the Pulse Repetition Frequency (PRF) in the 30 Hz to 50 Hz band in order to induce synchronization of oscillations synchronized in a plurality of target brain regions.

[0210] Furthermore, the composite stimulation is a signal having a strength for inducing membrane action potential and brain oscillation in a plurality of target brain regions, and this signal is not continuously applied, but has the form of a burst signal (Burst Signal) that is turned on (ON) / off (OFF) according to the PRF.

[0211] Also, the signal turned on (ON) according to the PRF is given as a stimulation according to the Burst Frequency, and at this time, the Burst Frequency (Burst) is set higher than the Pulse Repetition Frequency (PRF).

[0212] For example, a low frequency of 40 Hz for the on (ON) / off (OFF) PRF can be used (for the purpose of inducing gamma oscillation entrainment), and a high frequency of 10 kHz for the burst frequency of the on (ON) signal can be used (for the purpose of inducing membrane action potential and brain oscillation).

[0213] Here, since the signal by the composite stimulus is in the high-frequency (10 kHz) band, in order to measure the frequency (40 Hz) of the target EEG signal, it is separated through a low-pass filter. Also, since the strength of the electrical signal generated by the PRF is approximately 100 times lower than the strength of the target EEG signal, the brain wave signal induced by the PRF of the composite stimulus can be acquired in real time without interference.

[0214] That is, when performing electrical stimulation at 40 Hz to receive 40 Hz EEG in real time, real-time monitoring becomes impossible due to the interference between the electrical stimulation signal and the EEG signal.

[0215] Therefore, in the present invention, gamma entrainment is induced by transmitting high-frequency burst electrical stimulation through a 40 Hz PRF.

[0216] At this time, since the electrical stimulation signal by the burst is separated in the high-frequency band, the target 40 Hz EEG signal can be sensed in real time.

[0217] A more specific description will be given with reference to FIG. 4.

[0218] FIG. 4 is a drawing for explaining the closed-loop neurofeedback tACS stimulation method of the EEG signal base proposed by the present invention.

[0219] Referring to FIG. 4, the brain stimulation device (100) can use the tACS stimulation (400) method in a composite stimulation method of Burst Frequency (Burst) and Pulse Repetition Frequency (PRF) in order to separate the EEG frequency and the stimulation frequency band.

[0220] At this time, the tACS stimulus (400), which is a composite stimulus, is turned on (ON) / off (OFF) repeatedly according to a Pulse Repetition Frequency (PRF) whose given signal is a preset first frequency (410), and the signal turned on (ON) according to the first frequency (410) is given as a stimulus according to a Burst Frequency (Burst) which is a preset second frequency (420).

[0221] That is, the tACS stimulus (400) can be a first composite stimulus (combined signal) including a first frequency (410) and a second frequency (420).

[0222] As described above, the PRF (410) is applied to induce synchronization of oscillations synchronized in a plurality of brain regions of the subject, and the Burst Frequency (420) is applied to induce a membrane action potential and a brain oscillation in the plurality of brain regions of the subject.

[0223] Here, the Burst Frequency (420) is 10 kHz and will have a value higher than that of the Pulse Repetition Frequency (410) having a value of 40 Hz.

[0224] The Burst Frequency (420) moves neurons through a membrane action potential, induces brain oscillations, and enables them to communicate with each other.

[0225] By stimulating the Burst Frequency (420) at a high frequency, membrane activity can be easily induced, and oscillations can be rapidly induced. Further, to distinguish the complex stimulus given from the brain wave signal induced by the PRF (410) of the complex stimulus generated in the brain according to the Pulse Repetition Frequency (410), the Burst Frequency (420) is set to a frequency much higher than the 30 Hz to 50 Hz band.

[0226] Also, the Pulse Repetition Frequency (410) is given to induce the synchronization of the aforementioned synchronized gamma oscillations, and the activity stimulated by the Burst Frequency (420) is induced to be synchronized according to the gamma oscillation.

[0227] In particular, the Pulse Repetition Frequency (410) can be a method of transmitting a stimulus having a frequency of 30 Hz to 50 Hz to the subject in order to synchronize the synchronized gamma oscillations in a plurality of brain regions of the subject including the prefrontal cortex (PFC) and the hippocampus of the subject.

[0228] When a complex stimulus is given to the brain of the subject, the activity of neurons is induced by the Burst Frequency (420), irregular communication occurs, and the neurons induced to act in the period of the gamma wave region according to the PRF (410) here are synchronized to operate.

[0229] Therefore, in the present invention, brain wave synchronization is induced through high-frequency burst electrical stimulation, and gamma entrainment is induced through a 40 Hz PRF.

[0230] Furthermore, since the Burst Frequency (420) of the composite stimulus to be given is set to a frequency much higher than the 30 Hz to 50 Hz band, the brain wave signal induced by the PRF (410) of the composite stimulus can be distinguished from the given composite stimulus, the sensed composite stimulus can be ignored, and only the actually targeted brain waves can be distinguished and acquired.

[0231] Previously, since it was necessary to set the PRF to 40 Hz and sense the 40 Hz EEG, it was impossible to measure in real time. However, when a burst signal (Burst Signal) that is turned on (ON) / off (OFF) according to the Burst Frequency (420) as in the present invention is given as a composite stimulus according to the PRF (410) that induces synchronization of vibrations synchronized in the brain region, a difference of 40 dB or more (mathematically converted to 100 times or more) occurs, and it becomes possible to distinguish the signal by the composite stimulus from the brain wave signal induced by the PRF (410) of the composite stimulus, and only the targeted brain wave signal can be acquired.

[0232] The EEG sensor (141) can measure the brain waves of the brain induced by the stimulus, and the control unit (180) determines whether a reaction is elicited by using whether the brain waves measured by the EEG sensor (141) correspond to the output and waveform of the synchronized brain waves that appear only when the gamma oscillation is synchronized.

[0233] The control unit (180) extracts the characteristics of the measured brain waves by calculating the average and standard deviation of the power spectrum values of each frequency band, and the ratio of each average value by the combination of brain waves of gamma, alpha, beta, delta, and theta from the brain waves of the subject measured by the EEG sensor (141).

[0234] The EEG sensor (141) according to the present invention measures the EEG signal (500) in real time. For example, signals that are not used as the preliminary EEG (preEEG) signal (510) for the first 5 minutes can be sensed, and the RT EEG signal (520) used for real-time analysis for the next 20 minutes can be sensed. After measuring the RT EEG signal (520) for 20 minutes, it can be processed as a signal that is not used as the postEEG signal (530) again for 5 minutes.

[0235] As described above, the purpose of measuring EEG in real time in the present invention is to confirm whether the gamma oscillations synchronized in the brain region of the user (patient) are actually synchronized through the device provided by the present invention.

[0236] Generally, by applying a composite stimulus according to the PRF (410) of 40 Hz, the user (patient) may have synchronized gamma oscillations.

[0237] However, depending on the patient's depressive state, the synchronization of the synchronized gamma oscillations may occur at a frequency lower than 40 Hz.

[0238] Therefore, in the present invention, by applying a second composite stimulus in which at least one of the first frequency (410), the second frequency (420), and the output, waveform, and period of the stimulus based on the second frequency (420) is modified to the target brain, it is possible to induce the actual synchronized gamma oscillations to be synchronized.

[0239] As a specific example, when the PRF (410) is initially set to 40 Hz and the synchronization of gamma oscillations is not induced, the synchronization can be induced by reducing the signal to 38, 36, 34, 32 Hz. By continuously using the brain stimulation device (100) in this way, the brain function of the patient can be improved, and patients in whom synchronization is induced in the 32 Hz band can be made to have synchronization induced in the normal 40 Hz band.

[0240] Conversely, since there are also patients in whom gamma oscillation synchronization is induced at frequencies higher than 40 Hz, it is also possible to modify and stimulate the composite stimulus in the direction of increasing the frequency.

[0241] Referring to FIG. 4, through the tACS stimulation unit (313), a first composite stimulus (combined signal) can be given according to the PRF (410) for inducing synchronization of the synchronized oscillation in the brain region by a burst signal (Burst Signal) that is turned on (ON) / off (OFF) according to the Burst Frequency (420) (S1).

[0242] Also, the EEG sensor (141) can measure the brain wave signal by the first composite stimulus while the stimulus is being transmitted to the subject's brain (S2, S3).

[0243] At this time, the control unit (180) can distinguish and ignore the first signal by the first composite stimulus as noise among the signals measured (sensed) by the EEG sensor (141).

[0244] Furthermore, the control unit (180) can determine whether a reaction for synchronizing gamma oscillation is derived based on the second signal, which is the brain wave signal induced by the PRF (410) of the composite stimulus, among the signals measured by the EEG sensor (141) excluding the first signal (S4).

[0245] If the synchronized gamma oscillation is actually synchronized and a first reaction by the first composite stimulus is elicited (S4 - YES), the control unit (180) analyzes the correlation with the effect of depression treatment (improvement) for the patient's depressive state (indication) (S5), and can provide the user with a treatment monitoring reading model that outputs the analysis result in the form of a table, graph, etc. through the display unit (151) (S6).

[0246] On the other hand, when the synchronized gamma oscillations are actually not synchronized and the first response due to the first complex stimulus is not elicited (S4-NO), the control unit (180) modifies at least one of the first frequency (410), the second frequency (420), and the output, waveform, and period of the stimulus based on the second frequency (420), and controls the tACS stimulation unit (313) to transmit the second complex stimulus to the target brain (S7).

[0247] At this time, the first response relates to the synchronization of gamma oscillations synchronized in a plurality of regions of the brain, or the synchronization of any one of delta oscillations, theta oscillations, alpha oscillations, and beta oscillations.

[0248] Also, the first frequency (410) is a frequency from 30 Hz to 80 Hz for synchronizing gamma oscillations synchronized in a plurality of brain regions of the target including the prefrontal cortex (PFC) and the hippocampus of the target, a frequency from 14 Hz to 29 Hz for synchronizing beta oscillations, a frequency from 8 Hz to 13 Hz for synchronizing alpha oscillations, a frequency from 4 Hz to 7 Hz for synchronizing theta oscillations, or a frequency greater than 0 Hz and less than 4 Hz for synchronizing delta oscillations.

[0249] On the other hand, based on the fact that the magnitude of the first signal has a difference greater than or equal to a preset value from the magnitude of the second signal, signal interference due to the first complex stimulus can be ignored.

[0250] Ultimately, the present invention can improve the depressive state of a patient through a neurofeedback method that determines whether gamma oscillations actually occur based on the EEG signal acquisition technology during real-time tACS stimulation.

[0251] Real-time tACS-EEG Neurofeedback Algorithm

[0252] FIG. 5 is a block diagram of a real-time tACS-EEG Neurofeedback algorithm according to an embodiment of the present invention.

[0253] First, a real-time tACS-EEG Neurofeedback algorithm can be developed to induce gamma synchronization tailored to individuals optimized for each patient.

[0254] After going through the learning and verification processes, the real-time tACS-EEG Neurofeedback algorithm can be installed in the control unit (180).

[0255] Also, the control unit (180) can preprocess the brain wave signals from the EEG sensor (141) by the first composite stimulus (S10).

[0256] In the preprocessing stage (S10), when the control unit (180) receives the second signal among the brain wave signals from the EEG sensor (141) by the first composite stimulus, it applies a moving average filter on the time axis (S11), and then performs frequency axis conversion through FFT (S12), removes the DC voltage, and applies a band-pass filter for observing only the gamma band (S13) in sequence.

[0257] And after the preprocessing stage (S10), the control unit (180) can analyze the preprocessed second signal (S20).

[0258] In the analysis stage (S20), in order for the control unit (180) to determine whether the first reaction is elicited from the preprocessed second signal, power analysis of the frequency (S21) and analysis of the EEG signal (S22) can proceed simultaneously or sequentially.

[0259] Also, after the analysis stage (S20), the control unit (180) can induce gamma synchronization tailored to individuals optimized for each patient (S30).

[0260] In the gamma synchronization stage (S30), the control unit (180) monitors gamma synchronization (S31), quantitatively analyzes another neuron oscillation for gamma synchronization optimized for the patient for each PRF (410) (S32), and can vary the PRF (410) of the first composite stimulus for gamma synchronization according to the quantitative analysis result (S33).

[0261] On the other hand, the control unit (180) can store the monthly stimulation information / EEG data of the patient using the brain stimulation device (100) in the memory (160) and transmit the monthly stimulation information / EEG data to the server (200) through the wireless communication unit (110) (S40).

[0262] Thereby, when the user requests confirmation of the monthly stimulation information / EEG data by touching the user input unit (130) or the display unit (150), the brain stimulation device (100) can receive the monthly stimulation information / EEG data from the server (200) through the wireless communication unit (110) and provide the monthly stimulation information / EEG data to the user through the display unit (151).

[0263] In addition, the control unit (180) can store the first composite stimulus or the second composite stimulus information transmitted to the brain of the subject (patient) included in the monthly stimulation information in the memory (160) and transmit the first composite stimulus or the second composite stimulus information to the server (200) through the wireless communication unit (110).

[0264] Thereby, when the user requests confirmation of the stimulation history transmitted to the brain of the subject by touching the user input unit (130) or the display unit (150), the brain stimulation device (100) can receive the first composite stimulus or the second composite stimulus information transmitted to the brain of the subject (patient) from the server (200) through the wireless communication unit (110) and provide the stimulation history information to the user through the display unit (151).

[0265] Clinical trial

[0266] FIG. 6 is a diagram showing the clinical protocol of a clinical trial.

[0267] Referring to FIG. 6, a clinical trial was conducted to confirm whether depression improvement in patients was possible using the brain stimulation device (100).

[0268] The purpose of the clinical trial is to verify the neurophysiological, molecular biological, anatomical and kinematic effects of tACS stimulation on depression.

[0269] The subjects of the clinical trial were set as patients aged 40 years or older and less than 70 years old with anxiety / depression symptoms.

[0270] The sample size of the clinical trial was set at a minimum of 60 subjects based on a dropout rate of 15% during the exploratory clinical trial process, and the sample size of the confirmatory clinical trial was to be finally determined according to the exploratory pre - post comparison clinical results and the approval process of the Food and Drug Administration.

[0271] The random assignment of the clinical trial was carried out by the stratified block random assignment method, stratifying by gender (female and male) and age (less than or equal to 42 years old or above), and setting two or four blocks randomly mixed so that the test group and the control group were assigned at a ratio of 1:1. The test group (the brain stimulation device of the present invention to which parameters are applied), the control group (the external and internal designs are the same as those of the brain stimulation device, but since the internal current is cut off, a sham device to which no actual tACS - based combined stimulation is applied).

[0272] The effectiveness evaluation indicators of the clinical trial were as follows: the primary indicators were evaluated using BDI - II and LEIDS - R to evaluate depression, and the secondary indicators were evaluated by blood tests, the change amount of the heart rate variability index SDNN, LF / HF, the average amplitude and power of the induced slow waves (theta, delta, gamma) electroencephalogram.

[0273] For the statistical analysis of the clinical trial, the Independent t-test or chi-square test and Paired t-test were used to confirm the differences in basic demographic variables and baseline test results between the two groups (the test for the difference in means between the two groups was performed using the Independent t-test method, and the Paired t-test was applied when the observed values of the two populations were paired).

[0274] As a result of the clinical trial, it was confirmed that the test group using the brain stimulation device (100) equipped with the tACS stimulation unit (313) of the present invention had an effect of improving depression compared to the control group using a sham device.

[0275] Effects according to the present invention

[0276] The present invention can provide a personalized brain stimulation device capable of judging a patient's depressive state based on the patient's biological information and improving the patient's depressive state by transmitting a composite stimulation based on tACS (Transcranial alternating current stimulation) to the patient's brain.

[0277] Specifically, the present invention judges a patient's depression based on at least one of the patient's biological information, namely, Heart Rate Variability (HRV) information, electroencephalogram (EEG) information, heart rate information, stress information, body composition information, body weight information, oxygen saturation information, pulse information, blood pressure information, iris information, voice information, vein information, and electrocardiogram (ECG) information, and can provide a personalized brain stimulation device capable of improving the patient's depressive state by transmitting a composite stimulation based on tACS (Transcranial alternating current stimulation) to the patient's brain.

[0278] In addition, when the depression-related state of the patient is a Major Unipolar depression (MDD) state, the present invention can provide a personalized brain stimulation device capable of performing personalized brain stimulation that can enhance the gamma-level brain waves in the patient's brain waves through synchronization of gamma oscillations.

[0279] In addition, when the depression-related state of the patient is a stress-induced depressive disorder state, the present invention can provide a personalized brain stimulation device capable of performing personalized brain stimulation that can reduce the gamma-level brain waves in the patient's brain waves through synchronization of any one of delta, theta, alpha, and beta oscillations.

[0280] In addition, when the depression-related state of the patient is a Bipolar Disorder (BD) state, the present invention can provide a personalized brain stimulation device capable of performing personalized brain stimulation that can enhance the gamma-level brain waves when the gamma level in the patient's brain waves is the lowest and can reduce the gamma-level brain waves when the gamma-level brain waves in the patient's brain waves are the highest.

[0281] On the other hand, the embodiments of the present invention can be realized through various means. For example, the embodiments of the present invention can be realized by hardware, firmware, software, or a combination thereof.

[0282] In the case of realization by hardware, the method according to the embodiments of the present invention can be realized by one or more Application Specific Integrated Circuits (ASICs), Digital Signal Processors (DSPs), Digital Signal Processing Devices (DSPDs), Programmable Logic Devices (PLDs), Field Programmable Gate Arrays (FPGAs), processors, controllers, microcontrollers, microprocessors, etc.

[0283] In the case of implementation by firmware or software, the method according to the embodiments of the present invention can be implemented in the form of modules, procedures, functions, etc. that execute the above-described functions or operations. The software code can be stored in a memory unit and driven by a processor. The memory unit is located inside or outside the processor and can exchange data with the processor by various known means.

[0284] The detailed description of the preferred embodiments of the present invention disclosed as above is provided for those skilled in the art to implement and understand the present invention. Although the preferred embodiments of the present invention have been described above, those skilled in the art can understand that the present invention can be variously modified and changed without departing from the scope of the present invention. For example, those skilled in the art can use each configuration described in the above embodiments in a way of combining them with each other. Therefore, the present invention is not limited to the embodiments shown herein, but is intended to confer the broadest scope consistent with the principles and novel features disclosed herein.

[0285] The present invention can be embodied in other specific forms without departing from the spirit and essential characteristics of the present invention. Therefore, the above detailed description should not be construed as limiting in all respects, but should be regarded as exemplary. The scope of the present invention should be determined by a reasonable interpretation of the appended claims, and all changes within the equivalent scope of the present invention are included in the scope of the present invention. The present invention is not limited to the embodiments shown herein, but is intended to confer the broadest scope consistent with the principles and novel features disclosed herein. Also, embodiments can be constituted by combining claims without an explicit citation relationship in the claims, or can be included as new claims by amendments after filing.

Claims

1. A sensor unit that measures biological information of a subject, A control unit that determines whether the state of the subject corresponds to a first state among a plurality of preset states related to depression based on the biological information of the subject measured by the sensor unit, A stimulation unit that transmits different stimuli to the brain of the object according to the first state determined by the control unit in order to synchronize oscillations synchronized in a plurality of regions of the object's brain, including: The stimuli are A first stimulus for synchronizing gamma oscillations synchronized in a plurality of regions of the brain, a second stimulus for synchronizing any one of delta, theta, alpha, and beta oscillations synchronized in a plurality of regions of the brain, or a third stimulus combining the first stimulus and the second stimulus, The first, second, and third stimuli are transcranial alternating current stimulation (tACS), The transcranial alternating current stimulation is An individualized brain stimulation device characterized in that it is a first combined signal in which ON / OFF is repeated according to a preset first frequency, and a signal turned ON according to the first frequency is applied as a stimulus according to a preset second frequency.

2. The biological information is At least one of heart rate variability (HRV) information, electroencephalogram (EEG) information, heart rate information, stress information, body composition information, body weight information, oxygen saturation information, pulse information, blood pressure information, iris information, voice information, vein information, and electrocardiogram (ECG) information, The individualized brain stimulation device according to claim 1.

3. The plurality of preset states related to depression are Characterized in that it includes a depressive state due to stress, a major unipolar depression (MDD) state, and a bipolar disorder (BD) state, The individualized brain stimulation device according to claim 1.

4. The stimulation unit is When the first state of the subject determined by the control unit is the major depressive state, the first stimulus is transmitted to the brain, The transmission of the first stimulus is characterized by enhancing the gamma-level brain waves in the electroencephalogram of the subject through resonance of the gamma oscillation, the individualized brain stimulation device according to claim 3.

5. The stimulation unit transmits the second stimulus to the brain when the first state of the subject determined by the control unit is the depressive state due to stress, The transmission of the second stimulus is characterized by decreasing the gamma-level brain waves in the electroencephalogram of the subject through resonance of any one of the delta, theta, alpha, and beta oscillations, the individualized brain stimulation device according to claim 4.

6. The stimulation unit transmits the third stimulus to the brain when the first state of the subject determined by the control unit is the bipolar disorder state, when the first state of the subject is the bipolar disorder state and the gamma-level brain waves in the electroencephalogram of the subject are the lowest, the first stimulus is transmitted to the brain to enhance the gamma-level brain waves in the electroencephalogram of the subject, when the first state of the subject is the bipolar disorder state and the gamma-level brain waves in the electroencephalogram of the subject are the highest, the second stimulus is transmitted to the brain to decrease the gamma-level brain waves in the electroencephalogram of the subject, the individualized brain stimulation device according to claim 5.

7. The electroencephalogram information is the first electroencephalogram obtained in the brain, The sensor unit measures the second electroencephalogram of the subject in a state where the stimulus is transmitted to the brain, The control unit is characterized by determining whether a first reaction that resonates oscillations synchronized in a plurality of regions of the subject's brain is derived based on the second electroencephalogram of the subject measured by the sensor unit, the individualized brain stimulation device according to claim 2.

8. The first frequency is applied to induce resonance of oscillations synchronized in a plurality of brain regions of the subject, The second frequency is applied to induce membrane action potential and brain oscillation in a plurality of brain regions of the subject, characterized by being a value higher than the first frequency, the individualized brain stimulation device according to claim 1.

9. The control unit processing, as noise, a first signal based on the first composite stimulus among the signals measured by the sensor unit, determining whether a first response is derived based on a second signal obtained by excluding the first signal from the signals measured by the sensor unit, the individualized brain stimulation device according to claim 8. **Claim 10** The control unit when the first response based on the first composite stimulus is not derived, controlling the stimulation unit to transmit a second composite stimulus in which at least one of the output, waveform, and period of the stimulation based on the first frequency, the second frequency, and the second frequency is corrected to the brain of the subject, the individualized brain stimulation device according to claim 9. **Claim 11** The first response relates to resonance of any one of gamma oscillation, delta oscillation, theta oscillation, alpha oscillation, and beta oscillation synchronized in a plurality of regions of the brain, The first frequency is a frequency from 30 Hz to 80 Hz for resonating gamma oscillation synchronized in a plurality of brain regions of the subject including the prefrontal cortex (PFC) and the hippocampus of the subject, a frequency from 14 Hz to 29 Hz for resonating the beta oscillation, a frequency from 8 Hz to 13 Hz for resonating the alpha oscillation, a frequency from 4 Hz to 7 Hz for resonating the theta oscillation, or a frequency exceeding 0 Hz and less than 4 Hz for resonating the delta oscillation, the individualized brain stimulation device according to claim 10. **Claim 12** Based on the fact that the magnitude of the first signal has a difference of a preset value or more from the magnitude of the second signal, signal interference by the first composite stimulus is negligible, the individualized brain stimulation device according to claim 11.

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