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 drugs rather than oral drugs. Electronic drugs refer to medical devices that exert a new therapeutic effect by acting on cranial nerves with energies such as electricity, magnetic fields, and ultrasonic waves, 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 adjustment of cranial nerve functions.

[0003] Moreover, electronic drugs are electronic devices that can treat diseases by means of electrical stimulation without directly injecting drugs into the patient's body. Since they can select and stimulate only specific sites that require treatment, they have 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 drug treatment, and can also obtain a synergistic effect of treatment by combining with drugs.

[0004] Furthermore, among electronic drugs, there are antidepressant electronic drugs available in Japan that treat depression by normalizing frontal lobe function, which is the cause of depression. Stimulation methods for electronic drugs used to treat depression include tACS (transcranial alternating current stimulation), tDCS (transcranial direct current stimulation), DBS (deep brain stimulation), tMS (transcranial magnetic stimulation), and ECT (electroconvulsive therapy).

[0005] First, tACS is a method of transmitting microcurrents of less than 1 mA to the skull by attaching electrodes. It is used as a non-pharmacological treatment to improve symptoms such as anxiety, depression, insomnia, stress, headaches, and various types of pain. It is effective in regulating microglia cells, is safe due to its use of microcurrents, and has no side effects, making it suitable for medium- to long-term treatment. Furthermore, as a cutting-edge treatment with high compatibility with existing chemotherapy that promotes and / or suppresses hormone secretion, it can additionally induce sleep and improve sleep quality by maintaining a stable DMN in the brain itself, and improve sleep induction and sleep quality through the improvement of hormones (serotonin, melatonin, GABA, etc.). It can also stimulate brain tissue to restore neurochemicals to their pre-stress balance. The stimulation energy of tACS is AC (current flow), the stimulation form is pulsed or sinusoidal, the mechanism is brain entrainment by electric current, and its advantages include high patient convenience due to its verified safety (0.5 mA or 500 μA). However, while there is no pain due to skin impedance (SPU), which is a value that opposes the flow of current when voltage is applied in a circuit, it has the disadvantage of being less sensitive to stimulation because the transmission of stimuli is weak.

[0006] tDCS is a method of stimulating nerve cells in the cerebral cortex with a weak direct current by attaching electrodes to the head. It is a non-invasive brain stimulation method for recovering from sequelae of brain injury, and it can help improve brain function by adjusting the activity state of brain nerves through electrical stimulation. The stimulation energy of tDCS is DC (electric field), the stimulation mode is direct current (DC), and the mechanism is the maintenance of balance by activation (+) / inhibition (-) charges at the electrode site. Its advantages include a simple configuration and applicability (2 mA). However, it has the disadvantage of having a low therapeutic effect on depression because the difference between actual stimulation and simulated (sham) stimulation is not large, and although it is a non-invasive stimulation and easy to perform, there is a risk of burns at the electrode attachment site.

[0007] DBS (Deep Brain Stimulation) is a method that stimulates the activity of nerve cells by placing tiny electrodes, or needles, in deep brain nuclei. By applying electrical stimulation to nuclei in specific brain regions, it can disrupt pathological signals generated in those brain areas, thereby treating and improving symptoms of various diseases, including motor disorders. Furthermore, by placing tiny electrodes in deep brain nuclei and supplying the necessary power 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 nerve cells located at the electrode site can be blocked. This can then indirectly regulate the output of nerve cells by synaptic inhibition, that is, by activating axon terminals that have synaptic connections to nerve cells near the electrode. The stimulation energy of DBS is direct current (DC), pulse, or infrared (NIR), and the stimulation mode is pulse or sine wave. The mechanism is deep brain direct stimulation, and high-frequency stimulation (130 Hz) is effective. A key advantage is that high-frequency stimulation provides a higher therapeutic effect on depression compared to other electropharmaceutical stimulation methods. However, it has the disadvantage of requiring additional surgery to insert the needle into the deep nuclei of the brain.

[0008] tMS is a non-invasive method of 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. A strong magnetic field is generated near the head using an induction electromagnetic coil, and this field passes through the skull, stimulating nerve cells in the transcranial cortex. The activity level of the cerebral cortex can be increased or decreased depending on the speed of the magnetic field. For example, high-frequency stimulation can be used when the activity level of the cerebral cortex is low, such as in depression, while low-frequency stimulation can be used to adjust the activity level when it is too high, such as in anxiety disorders or mania. The stimulation energy of tMS is an edge current caused by the magnetic field. The stimulation mode is activation with a 10Hz pulse (5Hz iTBS) and inhibition with a 1Hz pulse. The mechanism is energy supply by the magnetic field and the resulting increase in gamma wave energy (gamma band power). A key advantage of tMS is that it is a non-invasive stimulation method and does not require surgery. However, there are limitations: the large size of the equipment makes it inconvenient for patients, and the non-invasive nature of the stimulation makes high-frequency electrical stimulation practically difficult.

[0009] ECT uses current flow (AC) as the stimulation energy, and the stimulation mode is pulsed or sinusoidal. The mechanism involves resetting nerve cells (neurons) with strong electrical stimulation (20-70 Hz). However, a problem is that anesthesia is always required to apply strong electrical stimulation to reset nerve cells.

[0010] On the other hand, tACS, one of the above-mentioned electroencephalography (EMG) methods, differs from the other EEG methods mentioned above in that it is possible to monitor the patient's electroencephalogram (EEG) in real time through brain synchronization using electrical currents, and through this, it is possible to provide practitioners with depression biomarkers that can confirm the patient's depressive state.

[0011] In other words, tACS-based electronic drugs for treating depression, unlike other stimulation-based electronic drugs, are expected to be more effective in treating depression in patients because they allow for individualized brain stimulation tailored to the patient's depressive state.

[0012] However, in order to provide tACS-based electronic drugs for the treatment of depression, it is necessary to improve the problem of tACS, which is that stimulus transmission is weak due to skin impedance. [Prior art documents] [Patent Documents]

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

[0014] (Patent Document 2) Japanese Published Patent No. 2014-502900 (Published February 6, 2014) [Overview of the Initiative] [Problems that the invention aims to solve]

[0015] The problem that this invention aims to solve is to provide a personalized brain stimulation device that can determine the patient's depressive state based on the patient's biological information and deliver a combination of tACS (Transcranial Alternating Current Stimulation)-based stimulation to the patient's brain to improve the patient's depressive state.

[0016] Specifically, the present invention aims to provide a personalized brain stimulation device that can determine a patient's depression based on at least one of the patient's biological information, such as heart rate variability (HRV), electroencephalogram (EEG), heart rate, stress, body composition, weight, oxygen saturation, pulse, blood pressure, iris, voice, venous information, and electrocardiogram (ECG), and then transmit a combination of tACS-based stimulation to the patient's brain to improve the patient's depressive state.

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

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

[0019] Furthermore, the present invention aims to provide a personalized brain stimulation device that can provide individualized brain stimulation when the patient's depression-related state is a bipolar disorder (BD) state, by enhancing the gamma level brainwaves when the gamma level is lowest in the patient's electroencephalogram (EEG) and decreasing the gamma level brainwaves when the gamma level is highest in the patient's EEG.

[0020] However, the technical problems that this invention aims to solve are not limited to those described above, and other technical problems not mentioned will be clearly understood by those with ordinary skill in the art to which this invention belongs from the following description. [Means for solving the problem]

[0021] A personalized brain stimulation device according to one embodiment of the present invention, which is a technical means for achieving the above objective, A sensor unit that measures the biological information of an object; A control unit that determines, based on the biological information of the object measured by the sensor unit, whether the state of the object corresponds to a first state among a plurality of pre-set states related to depression; and a stimulator that transmits stimuli to the brain of the object according to a first state determined by the control unit in order to synchronize vibrations synchronized in multiple regions of the brain of the object; The aforementioned stimulus is A first stimulus for synchronizing gamma oscillations synchronized in multiple regions of the brain, a second stimulus for synchronizing any of delta, theta, alpha, and beta oscillations synchronized in multiple regions of the brain, or a third stimulus which is a combination of the first and second stimuli. The first, second, and third stimuli are transcranial alternating current stimulation (tACS), The aforementioned transcranial alternating electrical stimulation is A first combined signal can be one in which an ON / OFF cycle is repeatedly performed according to a preset first frequency, and the signal that is ON according to the first frequency is applied as a stimulus 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 wave in the brain wave of the object 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 reduce the gamma-level brain wave in the brain wave of the object 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 wave in the brain wave of the object is the lowest, the first stimulation is transmitted to the brain to enhance the gamma-level brain wave in the brain wave of the object. When the first state of the object is the bipolar disorder state and the gamma-level brain wave in the brain wave of the object is the highest, the second stimulation is transmitted to the brain to reduce the gamma-level brain wave in the brain wave of the object.

[0027] Furthermore, the electroencephalogram information is a first electroencephalogram acquired by the brain, the sensor unit measures the second electroencephalogram of the object while the stimulus is being transmitted to the brain, and the control unit can determine, based on the second electroencephalogram of the object measured by the sensor unit, whether a first response is derived that synchronizes vibrations in multiple regions of the object's brain.

[0028] Furthermore, the first frequency is applied to induce synchronization of synchronized vibrations in multiple brain regions of the object, and the second frequency is applied to induce membrane action potentials and brain oscillations in multiple brain regions of the object, and can be higher than the first frequency.

[0029] Furthermore, the control unit can process the first signal from the first composite stimulus as noise among the signals measured by the sensor unit, and determine whether the first response is derived based on the second signal obtained by removing the first signal from the signals measured by the sensor unit.

[0030] Furthermore, if the first response based on the first composite stimulus is not derived, the control unit can control the stimulator to transmit a second composite stimulus to the brain of the object, which is obtained by modifying at least one of the first frequency, the second frequency, and the output, waveform, and period of the stimulus based on the second frequency.

[0031] Furthermore, the first response relates to the synchronization of any of the following vibrations synchronized in multiple brain regions of the object: gamma or delta vibration, theta vibration, alpha vibration, and beta vibration, wherein the first frequency may be a frequency of 30 Hz to 80 Hz for synchronizing gamma vibration synchronized in multiple brain regions of the object, including the prefrontal cortex (PFC) and hippocampus; a frequency of 14 Hz to 29 Hz for synchronizing beta vibration; a frequency of 8 Hz to 13 Hz for synchronizing alpha vibration; a frequency of 4 Hz to 7 Hz for synchronizing theta vibration; or a frequency greater than 0 Hz but less than 4 Hz for synchronizing delta vibration.

[0032] Furthermore, based on the fact that the magnitude of the first signal differs from the magnitude of the second signal by a predetermined value or more, it is possible to provide a personalized brain stimulation device in which signal interference by the first composite stimulus can be ignored. [Effects of the Invention]

[0033] According to one embodiment of the present invention, it is possible to provide an individualized brain stimulation device that can determine the patient's depressive state based on the patient's biological information and deliver a complex 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 provides an individualized brain stimulation device that can determine a patient's depression based on at least one of the patient's biological information, including heart rate variability (HRV), electroencephalogram (EEG), heart rate, stress, body composition, weight, oxygen saturation, pulse, blood pressure, iris, voice, venous, and electrocardiogram (ECG) information, and deliver a combination of tACS-based stimulation to the patient's brain to improve the patient's depressive state.

[0035] Furthermore, the present invention can provide a personalized brain stimulation device that can enhance gamma-level brain waves in the patient's electroencephalogram (EEG) through gamma oscillation synchronization when the patient's depression-related state is Major Unipolar Depression (MDD).

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

[0037] Furthermore, the present invention provides an individualized brain stimulation device that can provide individualized brain stimulation when the patient's depression-related state is a bipolar disorder (BD) state, by enhancing the gamma level brainwave when the gamma level is lowest in the patient's electroencephalogram (EEG) and decreasing the gamma level brainwave when the gamma level brainwave is highest in the patient's EEG.

[0038] However, the effects obtained by the present invention are not limited to those described above, and other effects not mentioned will be clearly understood by those with ordinary skill in the art to which the present invention pertains from the following description. [Brief explanation of the drawing]

[0039] [Figure 1] Figure 1 is a block diagram of a brain stimulation system according to one embodiment of the present invention. [Figure 2] Figure 2 is a diagram showing an example of a brain stimulation device. [Figure 3] Figure 3 is a diagram illustrating several predefined states related to depression. [Figure 4] Figure 4 is a diagram illustrating the EEG signal-based closed-loop neurofeedback tACS stimulation method proposed by the present invention. [Figure 5] Figure 5 is a block diagram of a real-time tACS-EEG neurofeedback algorithm according to one embodiment of the present invention. [Figure 6] Figure 6 is a diagram showing the clinical protocol for the clinical trial. [Modes for carrying out the invention]

[0040] Hereinafter, embodiments of the present invention will be described in detail with reference to the attached drawings, so that they can be easily implemented by a person with ordinary skill in the art to which the present invention pertains. However, since the description of the present invention is merely an example for structural or functional explanation, the scope of the present invention should not be interpreted as being limited by the embodiments described herein. In other words, since embodiments can be modified in various ways and can take on diverse forms, the scope of the present invention should be understood to include equivalents that can realize the technical idea. Furthermore, the purposes and effects shown in the present invention do not mean that a particular embodiment must include all of them, nor that it must include only those effects, so the scope of the present invention should not be understood as being limited by these.

[0041] The meanings of the terms used in this invention should be understood as follows:

[0042] Terms such as "first," "second," etc., are used to distinguish one component from another, and these terms do not limit the scope of rights. For example, the first component can be named the second component, and similarly, the second component can be named the first component. When it is stated that one component is "connected" to another component, it should be understood that it may be directly connected to the other component, or there may be other components in between. Conversely, when it is stated that one component is "directly connected" to another component, it should be understood that there are no other components in between. Other expressions describing the relationship between components, such as "between," "directly between," or "adjacent to" and "directly adjacent to," should be interpreted similarly.

[0043] Unless the context clearly indicates otherwise, singular expressions should be understood to include plural expressions, and terms such as “include” or “have” should be understood to indicate the existence of the described features, numbers, stages, actions, components, parts, or combinations thereof, without prejudice to the possibility of the existence or addition of one or more other features, numbers, stages, actions, components, parts, or combinations thereof.

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

[0045] Configuration of the brain stimulation system

[0046] The configuration of a preferred embodiment will be described in detail below with reference to the attached drawings.

[0047] Figure 1 is a block diagram of a brain stimulation system according to one embodiment of the present invention.

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

[0049] First, the brain stimulator (100) may 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 unit (160), an interface unit (170), a control unit (180), a power supply unit (190), and a stimulator unit (300), among others.

[0050] However, the components shown in Figure 1 are not necessarily required, and brain stimulation systems (1) with more or fewer components may be realized.

[0051] The above components will be explained in order below.

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

[0053] For example, the wireless communication unit (110) may 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 via a broadcast channel.

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

[0056] The aforementioned broadcast-related information may mean information relating to broadcast channels, broadcast programs, or broadcast service providers.

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

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

[0059] The broadcast receiving module (111) can receive digital broadcast signals using digital broadcasting 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, and 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-mentioned digital broadcasting systems but also with other broadcasting systems.

[0060] 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 to and from at least one of a base station, an external brain stimulator (100), or a server on a mobile communication network. The radio signals may include various forms of data associated with voice call signals, video call signals, or text / multimedia messages.

[0062] The wireless internet module (113) refers to a module for wireless internet connectivity, which can be built into or attached to the brain stimulator (100).

[0063] The aforementioned wireless internet technologies include WLAN (Wireless LAN) (Wi-Fi), Wibro (Wireless Broadband), WiMAX (World Interoperability for Microwave Access), and HSDPA (High Speed ​​Downlink Packet Access).

[0064] The short-range communication module (114) refers to a module for short-range communication. Technologies that can be used for this short-range communication include Bluetooth, RFID (Radio Frequency Identification), infrared communication (IrDA, Infrared Data Association), UWB (Ultra-Wideband), and ZigBee.

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

[0066] Referring to Figure 1, the A / V (Audio / Video) input section (120) is for inputting audio or video signals, and may include a camera (121) and a microphone (122), etc.

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

[0068] Image frames processed by the camera (121) can be stored in memory (160) or transmitted externally via wireless communication unit (110).

[0069] Depending on the usage environment, there may be two or more cameras (121).

[0070] The microphone (122) receives external acoustic signals via the microphone in recording mode, voice recognition mode, etc., and processes them into electrical audio data.

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

[0072] The microphone (122) can be equipped with various noise reduction algorithms to remove noise generated during the process of inputting external acoustic signals.

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

[0074] The user input section (130) can consist of a keypad, dome switch, touchpad (static / electrostatic), jog wheel, 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), whether or not there is user contact, the orientation of the brain stimulation system (1), and the acceleration / deceleration of the brain stimulation system (1), and generates sensing signals to control the operation of the brain stimulation system (1).

[0076] The sensing unit (140) can also sense whether or not power is being supplied to the power supply unit (190), whether or not external devices are connected to the interface unit (170), and so on.

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

[0078] In this invention, the subject's biological information is not limited, but may include at least one of the following: 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, venous information, and electrocardiogram (ECG) information.

[0079] Furthermore, the EGG sensor (141) refers to a sensor for measuring the brainwave information of a subject, and the bio-information sensor (142) may be a sensor for measuring bio-information other than the brainwave information that can be measured by the EGG sensor (141).

[0080] In other words, it is desirable that the sensing unit (140) be understood as a sensor for measuring the aforementioned biological information.

[0081] Electroencephalography (EEG) reveals that an individual's thoughts, emotions, and actions are generated by communication between nerve cells in the brain. EEG is a synchronized electrical wave produced by the transmission of signals between nerve cells in the cerebral cortex. EEG can be measured using electroencephalography (EEG), which measures the potential difference between surface electrodes located in specific areas of the scalp. The EEG shown in an EEG is the sum of the electrical activity of numerous cerebral cortical nerve cells beneath the surface electrodes.

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

[0083] Delta waves have a frequency range below 4 Hz and a large amplitude. They are waveforms that appear in deep sleep states where dreams do not occur.

[0084] Theta waves are brainwaves in the 4-7 Hz range that occur in certain sleep states and also appear during deep meditation. Theta waves are also known to be involved in the process of memory consolidation during sleep.

[0085] Alpha waves are brainwaves that appear in a state of wakefulness while quietly resting, with a frequency of approximately 8-13 Hz.

[0086] Beta waves, ranging from 14 to 29 Hz, are the rhythm of the activated cerebral cortex. They are the waveforms that appear when the cerebral cortex is in an aroused state and performing general cognitive thinking activities.

[0087] Gamma waves are high-frequency brainwaves with a frequency range of 30-80 Hz that appear during states of tension or excitement. They are known to appear during states of high concentration.

[0088] Electroencephalography (EEG) is a non-invasive technique for measuring brain waves. It involves fixing planar electrodes to the scalp using conductive paste and measuring the potential difference between the two electrodes.

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

[0090] Electroencephalograms (EEGs) are generated by synaptic currents in dendrites, which are electrical currents produced during 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 for that signal to reach electrodes attached to the scalp, it must pass through multiple layers of meninges, cerebrospinal fluid, skull, and scalp. Electrical recording of brain waves is possible because brain waves are the sum of signals generated when thousands of nerve cells are activated simultaneously. Therefore, the more synchronized the activity of nerve cells, the larger the amplitude and lower the frequency of the brain wave.

[0092] On the other hand, the output unit (150) is for generating outputs related to vision, hearing, or touch, and may 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), and the like.

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

[0094] The display unit (151) may include at least one of the following: liquid crystal display (LCD), thin film transistor-liquid crystal display (TFT LCD), organic light-emitting diode (OLED), flexible display, or 3D display.

[0095] These can be configured as transparent or light-transmitting types that allow the outside to be seen. These are sometimes called transparent displays, and typical examples of such transparent displays include TOLED (Transparent OLED). The rear structure of the display unit (151) can also be configured as a light-transmitting structure. With such a structure, the user can see an object located behind the brain stimulation system (1) body through the area occupied by the display unit (151) of the brain stimulation system (1) body.

[0096] Depending on the embodiment of the brain stimulation system (1), there may be two or more display units (151). For example, the brain stimulation system (1) may have multiple display units arranged separately or together on one surface, or they may be arranged on different surfaces.

[0097] When the display unit (151) and the touch sensor (hereinafter referred to as "touch sensor") form an interlayer structure (hereinafter referred to as "touchscreen"), the display unit (151) can be used not only as an output device but also as an input device. The touch sensor can take the form of, for example, a touch film, a touch sheet, or a touchpad.

[0098] The touch sensor can be configured to convert pressure applied to a specific part of the display unit (151) or changes in capacitance occurring 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 position and area of ​​the touch, but also the pressure applied at the time of the 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 sends the corresponding data to the control unit (180). This allows the control unit (180) to know which area of ​​the display unit (151) has been touched.

[0100] The proximity sensor can be positioned within the internal area of ​​the brain stimulation system (1) surrounded by the touchscreen, or near the touchscreen. The proximity sensor means a sensor that detects the presence or absence of an object approaching a predetermined detection surface, or an object present in the vicinity, without mechanical contact, using the force of an electromagnetic field or infrared light. Proximity sensors have a longer lifespan and higher applicability than contact sensors.

[0101] Examples of proximity sensors include transmissive photoelectric sensors, direct reflection photoelectric sensors, mirror reflection photoelectric sensors, high-frequency oscillation proximity sensors, capacitive proximity sensors, magnetic proximity sensors, and infrared proximity sensors. When the touchscreen is capacitive, it is configured to detect the proximity of the pointer by a change in the electric field caused by the pointer's proximity. In this case, the touchscreen (touch sensor) may also be classified as a proximity sensor.

[0102] The proximity sensor detects proximity touches and proximity touch patterns (e.g., proximity touch distance, proximity touch direction, proximity touch speed, proximity touch duration, proximity touch position, proximity touch movement state, etc.). The information corresponding to the detected proximity touch actions and proximity touch patterns can be output on the touchscreen.

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

[0104] The acoustic output module (152) may also output acoustic signals related to the functions performed by the brain stimulation system (1). Such acoustic output modules (152) may include receivers, speakers, buzzers, etc.

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

[0106] The alarm unit (153) can also output signals in forms other than video signals and audio signals, such as vibrations, to indicate the occurrence of an event.

[0107] The aforementioned video and audio signals can also be output through the display unit (151) and the sound output module (152), and these (151, 152) may sometimes be classified as part of the alarm unit (153).

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

[0109] For example, it's possible to synthesize and output different vibrations, or output them sequentially.

[0110] In addition to vibration, the haptic module (154) can generate various tactile effects through stimuli such as pin arrangements that move perpendicularly to the contacting skin surface, air jets and suction forces through nozzles and suction ports, friction against the skin surface, electrode contact, and electrostatic force, as well as effects from reproducing hot and cold sensations using heat-absorbing and heat-generating elements.

[0111] The haptic module (154) can transmit tactile effects through direct contact, and can also be implemented in a way that allows the user to feel the tactile effects through muscle sensation in their fingers, arms, etc. Two or more haptic modules (154) may be provided depending on the embodiment of the brain stimulation system (1).

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

[0113] Specifically, the projector module (155) may include a light source (not shown) that generates light (e.g., laser light) for outputting an image to the outside, an image generation means (not shown) for generating an image to be output to the outside using the light generated by the light source, and a lens (not shown) for magnifying and outputting the image to the outside at a constant focal length. The projector module (155) may also include a device (not shown) that can adjust the image projection direction by mechanically moving the lens or the entire module.

[0114] Projector modules (155) can be classified into CRT (Cathode Ray Tube) modules, LCD (Liquid Crystal Display) modules, and DLP (Digital Light Processing) modules depending on the type of elements used in the display. In particular, DLP modules are advantageous for miniaturizing projector modules (151) because they project an image generated by reflecting light from a light source off a DMD (Digital Micromirror Device) chip.

[0115] Preferably, the projector module (155) can be mounted vertically on the side, front, or back of the brain stimulation system (1). Of course, the projector module (155) can be mounted at any position on the brain stimulation system (1) as needed.

[0116] Furthermore, a head-up display (HUD, 156) refers to a device in a vehicle that projects information such as the vehicle's current speed, fuel level, and navigation guidance information as graphic images onto the window directly in front of the driver.

[0117] Furthermore, head-mounted displays (HMDs, 157) are representative devices that can output virtual reality information.

[0118] Virtual reality is a general term for human-computer interfaces that create three-dimensional content of specific environments and situations using computers, allowing users to interact with the 3D content as if they were actually experiencing their surroundings and environment.

[0119] Generally, the sense of depth that a person perceives arises from a combination of factors, including the degree to which the thickness of the lens changes depending on the position of the object being observed, the difference in angle between the two eyes and the object, the difference in the position and form of the object seen by the left and right eyes, parallax caused by the movement of the object, and various other psychological and memory-related effects.

[0120] The most important factor in how people perceive depth is binocular disparity, which arises from the fact that a person's eyes are separated by approximately 65 cm horizontally. In other words, binocular disparity causes us to see objects with a different angle, and this difference results in different images entering each eye. When these two images are transmitted to the brain via the retina, the brain accurately fuses these two pieces of information and recognizes them as the original 3D stereoscopic image.

[0121] Such three-dimensional 3D content is already widely used in various media fields and has been well-received by consumers. Examples include 3D movies, 3D games, and immersive displays.

[0122] As virtual reality technology and 3D content become more widespread, there is a multifaceted need to develop technologies that can provide more immersive virtual reality services.

[0123] Generally, an image display device refers to an image display device that uses a precise optical device to focus the image light generated at a very close position to the eye, so that a large virtual screen is formed at a distance, allowing the user to see an enlarged virtual image.

[0124] Furthermore, image display devices can be divided into two types: see-closed devices, which do not allow the surrounding environment to be seen and only allow the viewing of the image light emitted from the display element, and see-through devices, which allow the viewing of the surrounding environment through a window and simultaneously allow the viewing of the image light emitted from the display element.

[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 enable the provision of multimedia content. Due to the trend towards lighter and smaller digital devices, various wearable computers have been developed, and HMDs are also widely used.

[0126] HMD(157) goes beyond mere display functionality; it can be combined with augmented reality technology, N-screen technology, and other technologies to provide users with a variety of conveniences.

[0127] For example, if the HMD(157) is equipped with a microphone and speaker, the user can make phone calls while wearing the HMD(157). Also, for example, if the HMD(157) is equipped with a far-infrared camera(122), the user can capture images in a direction of their choice while wearing the HMD(157).

[0128] Furthermore, the memory unit (160) may store programs for processing and controlling the control unit (180), and can also function as a temporary storage unit for input and output data (e.g., messages, audio, still images, videos, etc.). The memory unit (160) can also store the frequency of use for each of the data. In addition, the memory unit (160) can store data related to various patterns of vibration and sound output when touch input is performed on the touchscreen.

[0129] The memory (160) may include at least one type of storage medium from among flash memory type, hard disk type, multimedia card micro type, card type memory (e.g., SD or XD memory), RAM (Random Access Memory), SRAM (Static Random Access Memory), ROM (Read-Only Memory), EEPROM (Electrically Erasable Programmable Read-Only Memory), PROM (Programmable Read-Only Memory), magnetic memory, magnetic disk, and optical disk. The brain stimulation system (1) can also operate in conjunction with web storage that performs the storage function of the memory (160) over the internet.

[0130] The interface unit (170) serves as a conduit for all external devices connected to the brain stimulation system (1). The interface unit (170) receives data from external devices, is supplied with power, and transmits it to the various components inside the brain stimulation system (1), and also enables data from inside the brain stimulation system (1) to be transmitted to external devices. For example, the interface unit (170) may 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, and an earphone port.

[0131] The identification module is a chip that stores various information for authenticating the right to use the brain stimulation system (1), and may include a User Identify Module (UIM), a Subscriber Identify Module (SIM), a Universal Subscriber Identity Module (USIM), etc. A device equipped with an identification module (hereinafter referred to as the "identification device") can be manufactured in smart card format. Therefore, the identification device can be connected to the brain stimulation system (1) through a port.

[0132] The interface unit can serve as a channel through which power from the cradle is supplied to the brain stimulation system (1) when the brain stimulation system (1) is connected to the cradle, or as a channel through which various command signals input by the user from the cradle are transmitted to the mobile device. The various command signals input from the cradle or the power supply can also function as signals to recognize that the mobile device is properly mounted on the cradle.

[0133] The control unit (controller, 180) typically 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 stimulator (100), but is not limited thereto, and is preferably implemented as an existing (or installed) application on a device owned by the user of the brain stimulator (100) (e.g., a smartphone, tablet, PC, etc.).

[0135] The power supply unit (190) is controlled by the control unit (180) and applies external and internal power supplies to supply the power necessary for the operation of each component.

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

[0137] In terms of hardware implementation, the embodiments described herein can be implemented using at least one of the following: 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, microcontrollers, microprocessors, or other electrical units for performing functions. In some cases, the embodiments described herein can be implemented as the control unit (180) itself.

[0138] In a software implementation, embodiments such as the procedures and functions described herein can be implemented as separate software modules. Each of these software modules can perform one or more of the functions and operations described herein. Software code can be implemented as a software application written in a suitable programming language. The software code can be stored in memory (160) and executed by a control unit (180).

[0139] Furthermore, the stimulator (300) provides functions to stimulate the user's brain through neuromodulation techniques, neurofeedback techniques, sensory stimulation techniques, and the like.

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

[0141] First, the electrical stimulation unit (310) may 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, stimulating the activity of nerve cells by positioning tiny electrodes in deep nuclei of the brain.

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

[0144] Deep brain stimulation (DBS) involves applying electrical stimulation to nuclei in specific brain regions, which can disrupt pathological signals generated in those brain areas, thereby treating and improving symptoms of various diseases, including motor disorders.

[0145] Deep brain stimulation involves placing tiny electrodes in deep nuclei of the brain and supplying the necessary power for activity from a pulse generator inserted into the chest in a manner similar to a cardiac pacemaker.

[0146] This allows for depolarization blockade, that is, the blocking of nerve output from nerve cells located at the electrode site.

[0147] Furthermore, synaptic inhibition, that is, activation of axon terminals that have synaptic connections to nerve cells near the electrode, can indirectly regulate the output of nerve cells.

[0148] Next, the tDCS stimulation unit (312) utilizes transcranial direct current stimulation, where electrodes are attached to the head and a weak direct current is used to stimulate nerve cells in the cerebral cortex.

[0149] The tDCS stimulation unit (312) is a non-invasive brain stimulation method aimed at recovering from sequelae caused by brain injury. It can help improve brain function by adjusting the activity state of cranial nerves through electrical stimulation.

[0150] The tACS (transcranial alternating current stimulation) stimulation unit (313) involves attaching electrodes to the skull and transmitting a minute current of less than 1 mA through them. It is used as a non-pharmacological treatment to improve symptoms such as anxiety, depression, insomnia, stress, headaches, and various types of pain.

[0151] tACS (transcranial alternating current stimulation) is effective in regulating microglial cells, is safe due to its use of microcurrents, has no side effects, and allows for medium- to long-term treatment.

[0152] Furthermore, it is a cutting-edge treatment that is highly compatible with existing chemotherapy regimens that promote and / or suppress hormone secretion.

[0153] When tACS (transcranial alternating current stimulation) stimulation is applied, it is possible to induce sleep and improve sleep quality by maintaining a stable default mode network (DMN) in the brain itself.

[0154] Furthermore, sleep induction and improvement of sleep quality are possible through the improvement of hormones (serotonin, melatonin, GABA, etc.).

[0155] Furthermore, it can stimulate brain tissue and restore neurochemicals to their pre-stress balance.

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

[0157] This is effective in treating neurological and psychiatric disorders such as Parkinson's syndrome and depression.

[0158] When a strong magnetic field is generated near the head using an induction electromagnetic coil, this magnetic field passes through the skull and stimulates nerve cells in the transcranial cortex.

[0159] In this process, the activity level of the cerebral cortex can be increased or decreased depending on the speed of the magnetic field. For example, high-frequency stimulation is used when the activity level of the cerebral cortex is low, such as in depression, while low-frequency stimulation is used to adjust the activity level when it is too high, such as in anxiety disorders or mania.

[0160] Furthermore, the ultrasound stimulation unit (330) utilizes ultrasound for therapeutic effects and is widely used in obstetrics and gynecology, orthopedics, dermatology, and other fields.

[0161] Ultrasound refers to sound waves with frequencies exceeding the limits of human hearing. Generally, healthy individuals can hear sound waves up to 20 kHz, and ultrasound refers to sound waves above this level. Ultrasound therapy utilizes such ultrasound for therapeutic purposes and is widely used in obstetrics and gynecology, orthopedics, dermatology, and other medical fields.

[0162] Ultrasound therapy can be broadly divided into high-intensity ultrasound (1000 W / cm² or higher) and low-intensity ultrasound (10-50 W / cm²). High-intensity ultrasound therapy selectively heats tissue and is mainly used for tumor treatment, while low-intensity ultrasound therapy heats subcutaneous tissue and is used for musculoskeletal treatments such as skin lifting, fracture treatment, and chondrocyte regeneration. Ultrasound therapy has the advantage of causing no skin damage and resulting in rapid recovery.

[0163] HIFU (High-Intensity Focused Ultrasound) is a method that uses the heat and energy generated when ultrasound beams transmitted from multiple directions are focused to cause necrosis or reduce the size of tumors without incision or surgery. It is used to treat uterine fibroids, prostate cancer, bone metastases, liver cancer, and other conditions.

[0164] LIFU (Low-Intensity Focused Ultrasound) is a method that uses heat to achieve a skin lifting effect through subcutaneous tissue necrosis. While its treatment mechanism is similar to high-intensity focused ultrasound, it differs in the intensity and area of ​​application.

[0165] LIPUS (Low-Intensity Pulsed Ultrasound) is a method that uses ultrasound waves to stimulate physical vibrations and activate cells in the treatment area, and is used in fracture treatment, cartilage cell regeneration therapy, and other applications.

[0166] Sonophoresis is a technique that uses low-frequency ultrasound to deliver drugs to the skin.

[0167] Furthermore, the light stimulation unit (340) can be used to stimulate the brain by irradiating light onto the head, and the Brain Photo Modulation method can be applied to it.

[0168] According to the photostimulation section (340), light in the 600-1000 nm range penetrates the cell wall and participates in the COX (Cytochrome c oxidase) respiratory chain within mitochondria.

[0169] This allows for increased synapse formation, increased angiogenesis, increased blood flow, prevention of inflammation, prevention of cell apoptosis, increased SOD levels, and decreased neuroexcitotoxicity.

[0170] Furthermore, the sensory stimulation unit (350) may 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, rather than directly stimulating the brain.

[0172] The visual stimulus portion (351) refers to radiation that can enter the naked eye and produce a sensation of light.

[0173] For example, the visual stimulation unit (351) typically uses a white stroboscope flash of about 100,000 lux, with the stroboscope bulb fixed approximately 20 cm in front of the eyes of the subject with their eyes closed, illuminating the entire field of view. The stimulation method involves applying stimuli in order from low frequency to high frequency for 10 seconds, then observing the brainwaves and the subject's condition for the following 10 seconds before moving on to the next stimulus.

[0174] Meanwhile, the server (200) can build a database and exchange information with the brain stimulator (100).

[0175] In this case, short-range or long-range communication can be applied between the server (200) and the brain stimulator (100).

[0176] Furthermore, the server (200) can form a network with medical institutions, receive information regarding the judgments and opinions of medical staff, and transmit it to the brain stimulator (100).

[0177] Structure of a brain stimulator

[0178] Figure 2 is a diagram showing an example of a brain stimulation device.

[0179] Referring to Figure 2, the brain stimulator (100) can be manufactured in a form that can be worn on the head so as to stimulate the brain of the subject (patient), as shown in Figure 3.

[0180] In this case, the brain stimulator (100) can be equipped with multiple sensing units (140) to measure the subject's biological information.

[0181] In one embodiment, the brain stimulator (100) can be configured with multiple sensing units (140) each implemented as an EGG sensor (141) for measuring electroencephalogram (EEG) information of the target, which is one of the target's biological information.

[0182] Furthermore, the electroencephalogram (EEG) information measured by the EGG sensor (141) is a first EEG acquired by the EGG sensor (141) from the target brain before the stimulator (300) transmits a stimulus to the target brain. The EGG sensor (141) can measure not only the first EEG but also the second EEG of the target while the stimulator (300) is transmitting a stimulus to the target brain.

[0183] The sensing unit (140) can be implemented as a bio-information sensor (142) that measures biological information of the target, excluding electroencephalogram (EGG) information, but in one embodiment, the EGG sensor (141) will be used as the basis for explanation.

[0184] Furthermore, the brain stimulator (100) may have multiple electrical stimulators (310) arranged to transmit stimuli to the brain of the subject for the purpose of improving the subject's depression.

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

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

[0187] The method for transmitting stimuli to the target brain through such a brain stimulator (100) is as follows:

[0188] Stimulation methods related to the present invention

[0189] First, the sensing unit (140) can measure the biological information of the subject (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 of several pre-set states related to depression shown in Figure 3.

[0191] Figure 3 is a diagram illustrating several predefined states related to depression.

[0192] In the present invention, the pre-defined depression-related states can include stress-induced depression, major unipolar depression (MDD), and bipolar disorder (BD), as shown in Figure 3.

[0193] On the other hand, the electrical stimulation unit (310) can transmit different stimuli to the target brain according to the target's first state determined by the control unit (180) in order to adjust the synchronized vibrations in multiple regions of the target brain.

[0194] In this invention, the stimulus transmitted to the target brain can be a first stimulus for adjusting gamma oscillations synchronized across multiple regions of the brain, a second stimulus for adjusting any of delta, theta, alpha, or beta oscillations synchronized across multiple regions of the brain, or a third stimulus which is a combination of the first and second stimuli.

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

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

[0197] The tACS stimulator (313) can transmit a first stimulus to the subject's brain if the first state of the subject, as determined by the control unit (180), is a major depressive state.

[0198] In this case, the transmission of the first stimulus is intended to enhance the gamma level brainwaves in the target brainwave through the adjustment of gamma oscillations, as shown in Figure 3.

[0199] The tACS stimulator (313) can transmit a second stimulus to the brain of a subject if the first state of the subject, as determined by the control unit (180), is a depressive state caused by stress.

[0200] At this time, the transmission of the second stimulus is intended to reduce the gamma level electroencephalogram in the target brainwave by modulating one of the delta, theta, alpha, or beta oscillations, as shown in Figure 3.

[0201] The tACS stimulator (313) can transmit a third stimulus to the subject's brain if the subject's first state, as determined by the control unit (180), is a bipolar disorder (BD) state.

[0202] More specifically, the tACS stimulator (313) can transmit a first stimulus to the subject's brain to enhance the gamma-level brain waves in the subject's brainwaves if the subject's first state is a bipolar disorder state and the gamma-level brainwaves in the subject's brainwaves are at their lowest.

[0203] Conversely, the tACS stimulator (313) can transmit a second stimulus to the subject's brain to reduce the gamma-level brain waves in the subject's brainwaves if the subject's first state is a bipolar disorder state and the gamma-level brainwaves are highest in the subject's electroencephalogram.

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

[0205] Inducing the synchronization (entrainment) of gamma wave oscillations (gamma oscillations) using tACS stimulation, as proposed in this invention, and sensing this in real time has been impossible in the past.

[0206] In other words, the GET (Gamma Entrainment Therapy) method requires technology to monitor brain signals in real time. However, gamma wave oscillations occur in the range of approximately 25-100 Hz, with 40 Hz being the target frequency. Since the method uses 40 Hz for oscillation, the oscillation frequency and the frequency that needs to be measured by EEG are in the same frequency range, making real-time monitoring technically impossible.

[0207] For example, when applying a 40Hz stimulus to synchronize gamma wave oscillations, EEG sensing also targets signals in the 40Hz band. This presents a major problem: it is impossible to distinguish whether the measured signal is noise from the stimulus or the target EEG signal. Consequently, the method proposed in this invention has not been implemented in the past.

[0208] In contrast, the present invention utilizes a combined stimulation method of Burst Frequency (Burst) and Pulse Repetition Frequency (PRF) as the tACS stimulation method for real-time EEG signal acquisition, which allows for the separation of the EEG frequency and the stimulation frequency band.

[0209] Furthermore, the frequency of the composite stimulus follows the Pulse Repetition Frequency (PRF) in the 30Hz to 50Hz range to induce synchronization of vibrations across multiple brain regions of the target.

[0210] Furthermore, the composite stimulus is a signal with sufficient intensity to induce membrane action potentials and brain oscillations in multiple target brain regions. This signal is not continuously applied, but rather takes the form of a burst signal that is turned on and off according to the PRF.

[0211] Furthermore, the signal that is turned ON according to the PRF is applied as a stimulus according to the Burst Frequency, and in this case, the Burst Frequency (Burst) is set higher than the Pulse Repetition Frequency (PRF).

[0212] For example, the PRF that is turned on / off can use a low frequency of 40 Hz (for the purpose of inducing gamma oscillation entrainment), while the burst frequency of the turned-on signal can use a high frequency of 10 kHz (for the purpose of inducing membrane action potential and brain oscillation).

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

[0214] In other words, if electrical stimulation is performed at 40Hz in order to receive a 40Hz EEG in real time, real-time monitoring becomes impossible due to interference between the electrical stimulation signal and the EEG signal.

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

[0216] In this case, the electrical stimulation signal caused by the burst is separated in the high-frequency band, allowing the target 40Hz EEG signal to be sensed in real time.

[0217] Please refer to Figure 4 for a more detailed explanation.

[0218] Figure 4 is a diagram illustrating the EEG signal-based closed-loop neurofeedback tACS stimulation method proposed by the present invention.

[0219] Referring to Figure 4, the brain stimulator (100) can utilize the tACS stimulation (400) method as a combined stimulation method of Burst Frequency (Burst) and Pulse Repetition Frequency (PRF) in order to separate the EEG frequency and the stimulation frequency band.

[0220] In this case, the composite stimulus, the tACS stimulus (400), is repeatedly turned on and off according to the Pulse Repetition Frequency (PRF), which is a preset first frequency (410) of the signal being applied. The signal that is turned on according to the first frequency (410) is then applied as a stimulus according to the Burst Frequency (Burst), which is a preset second frequency (420).

[0221] In other words, the tACS stimulus (400) can be a first combined signal containing a first frequency (410) and a second frequency (420).

[0222] As described above, PRF(410) is applied to induce synchronized oscillations in multiple brain regions of the target, and Burst Frequency(420) is applied to induce membrane action potentials and brain oscillations in the same multiple brain regions of the target.

[0223] Here, the Burst Frequency (420) is 10 kHz, which is higher than the Pulse Repetition Frequency (410), which has a value of 40 Hz.

[0224] Burst frequency (420) stimulates neurons through membrane action potentials, inducing brain oscillations and enabling 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. Furthermore, in order to distinguish the electroencephalogram signal induced by the PRF (410) of the complex stimulation generated in the brain according to the Pulse Repetition Frequency (410) from the complex stimulation being applied, the Burst Frequency (420) is set to a frequency much higher than the 30Hz to 50Hz band.

[0226] Furthermore, the Pulse Repetition Frequency (410) is provided to induce the synchronization of the aforementioned synchronized gamma oscillations, so that the activity stimulated by the Burst Frequency (420) is induced to synchronize according to the gamma oscillations.

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

[0228] When a complex stimulus is applied to the target brain, the Burst Frequency (420) induces neuronal activity, resulting in irregular communication. Neurons whose activity is induced with a gamma wave period following the PRF (410) then begin to operate in sync.

[0229] Therefore, in this invention, electroencephalogram (EEG) synchronization is induced through high-frequency burst electrical stimulation, and gamma synchronization (entrainment) is induced through 40Hz PRF.

[0230] Furthermore, since the Burst Frequency (420) of the applied composite stimulus is set to a much higher frequency than the 30Hz to 50Hz band, it is possible to distinguish the electroencephalogram (EEG) signal induced by the PRF (410) of the composite stimulus from the applied composite stimulus itself. This allows the sensed composite stimulus to be ignored, and only the target EEG signal to be distinguished and acquired.

[0231] Previously, it was impossible to measure in real time because it was necessary to set the PRF to 40Hz and sense the EEG at 40Hz. However, as in the present invention, when a burst signal that is turned on / off according to the Burst Frequency (420) is applied as a composite stimulus according to the PRF (410) for inducing synchronized vibration synchronization in brain regions, a difference of 40dB or more (more than 100 times mathematically) is generated, making it possible to distinguish between the signal from the composite stimulus and the electroencephalogram signal induced by the PRF (410) of the composite stimulus, and to acquire only the target electroencephalogram signal.

[0232] The EEG sensor (141) can measure brainwaves induced in response to stimuli, and the control unit (180) determines whether a response is elicited by using whether the brainwaves measured by the EEG sensor (141) correspond to the output and waveform of synchronized brainwaves that appear only when gamma oscillations are synchronized.

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

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

[0235] As mentioned above, the purpose of measuring EEG in real time in this invention is to allow the user (patient) to confirm, through the device provided by this invention, whether synchronized gamma oscillations in brain regions have actually been synchronized.

[0236] Generally, by applying complex stimuli according to a 40Hz PRF (410), the user (patient) may be able to synchronize their gamma oscillations.

[0237] However, depending on the patient's depressive state, the synchronized gamma oscillation may be tuned at frequencies lower than 40 Hz.

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

[0239] As a specific example, if gamma oscillation synchronization is not induced when the PRF(410) is initially set to 40Hz, synchronization can be induced by reducing the signal to 38, 36, 34, and 32Hz. By continuously using the brain stimulator (100) in this way, the patient's brain function can be improved, and patients who are induced to synchronize in the 32Hz band can be made to synchronize in the normal range of the 40Hz band.

[0240] Conversely, some patients can induce gamma oscillation synchronization at frequencies higher than 40 Hz, so it is possible to modify the complex stimulation by increasing the frequency.

[0241] Referring to Figure 4, a first combined signal can be delivered via the tACS stimulator (313) according to the PRF (410) to induce synchronization of oscillatory signals synchronized in brain regions, with the Burst Signal being turned on / off according to the Burst Frequency (420) (S1).

[0242] Furthermore, the EEG sensor (141) can measure the electroencephalogram (EEG) signal from the first composite stimulus while the stimulus is being transmitted to the target brain (S2, S3).

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

[0244] Furthermore, the control unit (180) can determine whether a response that synchronizes gamma oscillations can be derived based on the second signal, which is an electroencephalogram 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 oscillations are actually synchronized and the first response is elicited by the first composite stimulus (S4-YES), the control unit (180) can analyze the correlation between the patient's depressive state (indication) and the effect of depression treatment (improvement) (S5), and provide the user with a treatment monitoring image interpretation model that outputs the analysis results in tables, graphs, etc., via the display unit (151) (S6).

[0246] In contrast, if the synchronized gamma oscillations are not actually synchronized and the first combined stimulus does not elicit a first response (S4-NO), the control unit (180) can control the tACS stimulator (313) to transmit a second combined stimulus to the target brain, which has been modified to include a first frequency (410), a second frequency (420), and at least one of the output, waveform, and period of the stimulus based on the second frequency (420) (S7).

[0247] In this case, the first response concerns the synchronization of gamma oscillations, or the synchronization of one of the following oscillations—delta oscillation, theta oscillation, alpha oscillation, or beta oscillation—in multiple regions of the brain.

[0248] Furthermore, the first frequency (410) can be a frequency of 30 Hz to 80 Hz for synchronizing gamma oscillations synchronized in multiple brain regions of the subject, including the prefrontal cortex (PFC) and hippocampus; a frequency of 14 Hz to 29 Hz for synchronizing beta oscillations; a frequency of 8 Hz to 13 Hz for synchronizing alpha oscillations; a frequency of 4 Hz to 7 Hz for synchronizing theta oscillations; or a frequency greater than 0 Hz but less than 4 Hz for synchronizing delta oscillations.

[0249] On the other hand, signal interference from the first composite stimulus can be ignored if the magnitude of the first signal is greater than or equal to a predetermined value.

[0250] In short, the present invention can improve a patient's depressive state through a neurofeedback method that determines whether gamma oscillation is actually occurring based on EEG signal acquisition technology during real-time tACS stimulation.

[0251] Real-time tACS-EEG Neurofeedback algorithm

[0252] Figure 5 is a block diagram of a real-time tACS-EEG neurofeedback algorithm according to one embodiment of the present invention.

[0253] First, we can develop a real-time tACS-EEG neurofeedback algorithm that can induce personalized gamma synchronization optimized for each patient.

[0254] The real-time tACS-EEG neurofeedback algorithm can be implemented in the control unit (180) after undergoing a learning and validation process.

[0255] Furthermore, the control unit (180) can preprocess the electroencephalogram signal from the EEG sensor (141) due to the first composite stimulus (S10).

[0256] In the preprocessing stage (S10), when the control unit (180) receives the second signal of the electroencephalogram signal from the first composite stimulus from the EEG sensor (141), it can sequentially perform the following processes: apply a moving average filter on the time axis (S11), then perform a frequency axis transformation through FFT (S12), remove the rated voltage, and apply a bandpass filter to observe only the gamma band (S13).

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

[0258] In the analysis stage (S20), the control unit (180) may simultaneously or sequentially perform frequency power analysis (S21) and EEG signal analysis (S22) to determine whether a first reaction can be derived from the pre-processed second signal.

[0259] Furthermore, after the analysis step (S20), the control unit (180) can induce personalized gamma synchronization optimized for each patient (S30).

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

[0261] Meanwhile, the control unit (180) can store monthly stimulation information / EEG data of patients using the brain stimulator (100) in memory (160) and transmit the monthly stimulation information / EEG data to the server (200) via the wireless communication unit (110) (S40).

[0262] As a result, when a user requests to check monthly stimulation information / EEG data by touching the user input unit (130) or the display unit (150), the brain stimulator (100) can receive monthly stimulation information / EEG data from the server (200) via the wireless communication unit (110) and provide the monthly stimulation information / EEG data to the user via the display unit (151).

[0263] Furthermore, the control unit (180) can store the first or second composite stimulus information transmitted to the subject's (patient's) brain, which is included in the monthly stimulus information, in the memory (160), and transmit the first or second composite stimulus information to the server (200) via the wireless communication unit (110).

[0264] As a result, when a user requests confirmation of the stimulation history transmitted to the target brain by touching the user input unit (130) or the display unit (150), the brain stimulator (100) can receive first or second complex stimulation information transmitted to the target (patient) brain from the server (200) via the wireless communication unit (110) and provide the stimulation history information to the user via the display unit (151).

[0265] Clinical trials

[0266] Figure 6 shows the clinical protocol for the clinical trial.

[0267] Referring to Figure 6, a clinical trial was conducted to determine whether it was possible to improve patients' depression using a brain stimulation device (100).

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

[0269] The clinical trial included patients aged 40 to under 70 with anxiety / depressive symptoms.

[0270] The sample size for clinical trials will be set at a minimum of 60 participants, based on a 15% dropout rate criterion during the exploratory clinical trial process. The sample size for confirmatory clinical trials will be finalized in accordance with the results of the exploratory before-and-after clinical trials and the approval process of the Korea Food and Drug Administration.

[0271] Random assignment for the clinical trial involved a test group (a brain stimulator of the present invention with applied parameters) and a control group (a sham device with the same external and internal design as the brain stimulator, but with the internal current blocked, so that the actual tACS-based composite stimulation was not applied). Participants were stratified by sex (female and male) and age (under or over 42 years) using a stratified block randomization method, with two or four blocks randomly mixed to ensure a 1:1 ratio between the test and control groups.

[0272] The efficacy evaluation metrics for the clinical trial included primary indicators such as BDI-II and LEIDS-R to assess depression, and secondary indicators such as blood tests, heart rate variability indices (SDNN), LF / HF change, and mean amplitude and power of led slow-wave (theta, delta, gamma) electroencephalograms.

[0273] Statistical analysis of the clinical trials used independent t-tests or chi-squared tests and paired t-tests to examine differences in basic demographic variables and baseline test results between the two groups (the independent t-test was used to test the difference in means between the two groups, and the paired t-test was applied when the observations from the two populations were paired).

[0274] Clinical trial results confirmed that the group using the brain stimulator (100) equipped with the tACS stimulator (313) of the present invention showed a greater effect in improving depression compared to the control group using a sham device.

[0275] Effects according to the present invention

[0276] The present invention provides a personalized brain stimulation device that can improve a patient's depressive state by determining the patient's depressive state based on the patient's biological information and transmitting a tACS (transcranial alternating current stimulation)-based complex stimulation to the patient's brain.

[0277] Specifically, the present invention provides a personalized brain stimulation device that can improve a patient's depressive state by determining the patient's depression based on at least one of the patient's biological information, including heart rate variability (HRV), electroencephalogram (EEG), heart rate, stress, body composition, weight, oxygen saturation, pulse, blood pressure, iris, voice, venous, and electrocardiogram (ECG) information, and by transmitting a transcranial alternating current stimulation (tACS)-based composite stimulation to the patient's brain.

[0278] Furthermore, the present invention provides a personalized brain stimulation device that can enhance gamma-level brain waves in the patient's electroencephalogram through gamma oscillation synchronization, when the patient's depression-related state is a major unipolar depression (MDD) state.

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

[0280] Furthermore, the present invention provides a personalized brain stimulation device that can provide personalized brain stimulation, which, when a patient's depression-related state is a bipolar disorder (BD) state, enhances the gamma level brainwave when the gamma level is lowest in the patient's electroencephalogram (EEG) and reduces the gamma level brainwave when the gamma level brainwave is highest in the patient's EEG.

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

[0282] In the case of hardware implementation, the method according to the embodiment of the present invention can be implemented using one or more 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, microcontrollers, microprocessors, etc.

[0283] In the case of implementation by firmware or software, the method according to the embodiment of the present invention can be implemented in the form of a module, procedure, or function that performs the aforementioned function or operation. The software code can be stored in a memory unit and driven by a processor. The memory unit may be located inside or outside the processor and may exchange data with the processor by various known means.

[0284] The detailed description of preferred embodiments of the present invention disclosed above is provided for those skilled in the art to practice and understand the present invention. While preferred embodiments of the present invention have been described above with reference, those skilled in the art will understand that the present invention can be modified and altered in various ways without departing from the scope of the invention. For example, those skilled in the art can utilize the configurations described above by combining them with each other. Thus, the present invention is not limited to the embodiments shown herein, but seeks to provide the broadest possible 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 features of the invention. Therefore, the above detailed description should not be interpreted restrictively in all respects, but rather as illustrative. The scope of the invention should be determined by a reasonable interpretation of the appended claims, and all modifications within the equivalent scope of the invention are included within the scope of the invention. The present invention is not limited to the embodiments shown herein, but seeks to provide the broadest possible scope consistent with the principles and novel features disclosed herein. Furthermore, embodiments can be formed by combining claims that are not explicitly referenced in the claims, or by including new claims through amendments after filing.

Claims

1. A sensor unit that measures the target's biological information, A control unit that determines whether the state of the target falls into one of a set of predetermined states related to depression, based on the biological information of the target measured by the sensor unit, In order to synchronize the oscillations of electrical activity generated by nerve cells in multiple regions of the target brain, a stimulator transmits different stimuli to the target brain according to the state of the target determined by the control unit, Includes, The aforementioned stimulus is A first stimulus for synchronizing the gamma oscillations of electrical activity generated by nerve cells in multiple regions of the brain; a second stimulus for synchronizing any of the delta, theta, alpha, and beta oscillations of electrical activity generated by nerve cells in multiple regions of the brain; or a third stimulus which is a combination of the first and second stimuli. The first, second, and third stimuli are transcranial alternating current stimulation (tACS), The aforementioned transcranial alternating electrical stimulation is A first composite stimulus is provided in which a burst signal is repeatedly turned on and off according to a preset first frequency, the burst signal being an electrical stimulus that vibrates at a second frequency, and when the burst signal is on, the burst signal is applied to the brain as a stimulus. The aforementioned predefined states related to depression include stress-induced depressive disorder, major depressive disorder (MDD) state, and bipolar disorder (BD) state. When the state of the target determined by the control unit is a depressive disorder state caused by stress, the stimulator delivers the second stimulus to the brain. The transmission of the second stimulus reduces the intensity of the gamma frequency band brain waves in the target brainwave through the synchronization of the electrical activity oscillations generated by one of the delta, theta, alpha, and beta oscillation neurons. A personalized brain stimulation device characterized by the following features.

2. The aforementioned biometric information is A personalized brain stimulator according to claim 1, characterized in that it includes at least one of the following: 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, venous information, and electrocardiogram (ECG) information.

3. The aforementioned stimulating part is, If the state of the target as determined by the control unit is a major depressive state, the first stimulus is transmitted to the brain. The transmission of the first stimulus is The individualized brain stimulation device according to claim 1, characterized in that it enhances the intensity of brain waves in the gamma frequency band of the target brain waves by synchronizing gamma oscillations in the electrical activity generated by the nerve cells.

4. The aforementioned stimulating part is, If the state of the target as determined by the control unit is a bipolar disorder state, the third stimulus is transmitted to the brain. If the subject's condition is bipolar disorder, and the intensity of the brainwaves in the gamma frequency band is lower than the intensity of the subject's brainwaves in the delta frequency band, theta frequency band, alpha frequency band, and beta frequency band, then the first stimulus is transmitted to the brain to enhance the intensity of the brainwaves in the gamma frequency band of the subject's brainwaves. The individualized brain stimulation device according to claim 3, characterized in that, if the subject's condition is a bipolar disorder state, and the intensity of the brainwaves in the gamma frequency band is higher than the intensity of the subject's brainwaves in the delta frequency band, theta frequency band, alpha frequency band, and beta frequency band, the second stimulus is transmitted to the brain to reduce the intensity of the brainwaves in the gamma frequency band in the subject's brainwaves.

5. The aforementioned electroencephalogram information is This is the first brainwave acquired in the aforementioned brain, The aforementioned sensor unit is The second electroencephalogram of the subject is measured while the stimulus is being transmitted to the brain. The control unit, The individualized brain stimulation device according to claim 2, characterized in that, based on the second brainwave of the target measured from the sensor unit, it determines whether any of the gamma oscillation, delta oscillation, theta oscillation, and beta oscillation in the electrical activity generated by the nerve cells, which are synchronized among multiple regions of the target's brain, are derived in a synchronized manner.

6. The first frequency is, This method is applied to induce synchronization of the oscillations of electrical activity generated by nerve cells in multiple brain regions of the aforementioned target. The second frequency is, This method is applied to induce membrane action potential and brain oscillation between multiple target brain regions. The individualized brain stimulation device according to claim 1, characterized in that the frequency is higher than the first frequency.

7. The control unit, The sensor unit processes the first signal based on the first composite stimulus from the signals it has measured as noise. The individualized brain stimulation device according to claim 6, characterized in that, based on a second signal obtained by excluding the first signal from the signals measured by the sensor unit, it determines whether any of the gamma oscillation, delta oscillation, theta oscillation, and beta oscillations in the electrical activity generated by the nerve cells, which are synchronized among multiple regions of the target brain, are derived.

8. The control unit, The individualized brain stimulator according to claim 7, characterized in that, if no gamma oscillation, delta oscillation, theta oscillation, or beta oscillation is derived in the electrical activity generated by the nerve cells that is synchronized among multiple regions of the target brain based on the first composite stimulation, the stimulator controls the stimulator to transmit a second composite stimulation to the target brain, which is modified by at least one of the first frequency, the second frequency, and the output, waveform, and period of the stimulation based on the second frequency.

9. The first frequency is, The individualized brain stimulation device according to claim 8, characterized in that the frequencies are 30 Hz to 80 Hz for synchronizing the gamma oscillations of electrical activity generated by the nerve cells among a plurality of brain regions of the target, including the prefrontal cortex (PFC) and hippocampus of the target; 14 Hz to 29 Hz for synchronizing the beta oscillations of electrical activity generated by the nerve cells; 8 Hz to 13 Hz for synchronizing the alpha oscillations of electrical activity generated by the nerve cells; 4 Hz to 7 Hz for synchronizing the theta oscillations of electrical activity generated by the nerve cells; or a frequency greater than 0 Hz and less than 4 Hz for synchronizing the delta oscillations of electrical activity generated by the nerve cells.

10. The individualized brain stimulation device according to claim 9, characterized in that, based on the fact that the magnitude of the first signal differs from the magnitude of the second signal by a predetermined value or more, the first signal resulting from the first composite stimulus is processed as noise.

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