Apparatus and method for providing gamma brainwave synchronization for mild cognitive impairment patient

Abstract

The present invention relates to an apparatus and a method for providing gamma brainwave synchronization for mild cognitive impairment patients, which can maximize a treatment response of mild cognitive impairment patients by activating brainwaves in a gamma band through light stimulation to mild cognitive impairment patients. The apparatus for providing gamma brainwave synchronization for mild cognitive impairment patients comprises: a light irradiation unit for providing visual stimulation to a subject by irradiating blinking light at a frequency of a gamma band; a brainwave measurement unit for measuring a brainwave in a gamma band induced in the brain of the subject while the visual stimulation is provided to the subject through the light irradiation unit; and a control unit for selecting, as an optimal frequency, a center frequency at which the synchronization of the brainwave in the gamma band appears the strongest, and controlling the light irradiation unit to provide the visual stimulation to the subject at the selected optimal frequency.

Description

Device and method for providing gamma brainwave entrainment for patients with mild cognitive impairment

[0001] [Cross-reference to related applications]

[0002] This application claims priority to Republic of Korea Patent Application No. 10-2024-0098036, filed July 24, 2024, the entire contents of which are incorporated herein by reference.

[0003] The present invention relates to a device and method for providing gamma brainwave entrainment for patients with mild cognitive impairment, and more particularly, to a device and method for providing gamma brainwave entrainment for patients with mild cognitive impairment, which activates gamma band brainwaves through optical stimulation to maximize the treatment response of patients with mild cognitive impairment.

[0004] [National Research and Development Project Supporting This Invention]

[0005] [Project ID] 1711189819

[0006] [Assignment Number] 2017R1A5A1014708

[0007] [Ministry Name] Ministry of Science and ICT

[0008] [Name of Project Management (Specialist) Institution] National Research Foundation of Korea

[0009] [Research Project Name] Group Research Support

[0010] [Research Project Name] Center for Healthcare Engineering for Body-Attached Light Therapy

[0011] [Name of the project performing organization] Korea Advanced Institute of Science and Technology

[0012] [Research Period] March 1, 2023 - February 29, 2024

[0013] Mild Cognitive Impairment (MCI) is a condition in which memory or other cognitive functions decline significantly enough to be confirmed through objective tests, but the ability to perform daily life activities is preserved, so it is not dementia yet.

[0014] Mild cognitive impairment is considered a high-risk group that may progress to Alzheimer's disease (AD).

[0015] A recent study observed that gamma waves in brain waves were reduced in Alzheimer's patients compared to the general population.

[0016] Gamma waves are brain waves that belong to the highest frequency band among the brain's electrical activities, and their frequency range is approximately between 25 Hz and 100 Hz, and the 30 Hz to 40 Hz band is commonly referred to.

[0017] These gamma waves are involved in attention, learning, memory, sensory perception, object recognition, and complex information processing, and are involved in both bottom-up and top-down neural regulation.

[0018] There is currently no cure for Alzheimer's disease, but various medications and non-medication treatments can help alleviate symptoms and slow its progression.

[0019] Drugs used in drug treatment include cholinesterase inhibitors, antioxidants, and NMDA (N-methyl-D-aspartate) receptor antagonists.

[0020] Non-pharmacological treatments include transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), which aim to improve cognitive function and slow the progression of Alzheimer's disease by stimulating or modulating neural circuits.

[0021] Transcranial magnetic stimulation is a method that uses a strong magnetic field to stimulate specific areas of the brain. The magnetic field passes through brain tissue, inducing an electric current and modulating neuronal activity.

[0022] Transcranial direct current stimulation is a method of stimulating or inhibiting specific areas of the brain by passing a weak direct current through the skull. The anode increases the excitability of neurons, and the cathode decreases excitability.

[0023] However, conventional treatments have problems such as difficult to control side effects, high costs, and unproven effectiveness.

[0024] Meanwhile, one of the treatment methods for patients with mild cognitive impairment is the gamma brainwave entrainment technique.

[0025] Gamma brainwave entrainment technique is a technique that induces brainwaves in the gamma frequency band through external stimulation.

[0026] As previously explained, patients with Alzheimer's disease or mild cognitive impairment tend to have decreased gamma brainwave activity. Gamma brainwave entrainment is a method that aims to improve cognitive function by increasing the activity of the brain's gamma frequency band through external periodic stimulation.

[0027] For example, conventionally, gamma brain waves are induced using light that flashes at a specific frequency (e.g., 40 Hz).

[0028] As mentioned above, conventionally, gamma brain waves are induced using a specific frequency (e.g., 40 Hz), but gamma brain wave induction using a specific frequency has a problem in that inconsistent results are produced due to individual differences in center frequency (CF).

[0029] The present invention has been made to solve the above-mentioned conventional problems, and the purpose of the present invention is to provide a device and method for providing gamma brainwave entrainment for a patient with mild cognitive impairment, which selects a center frequency at which brainwave entrainment is most strongly shown in a subject among a plurality of center frequencies as an optimal frequency, and activates the gamma band brainwaves of the subject using the selected optimal frequency, thereby maximizing the treatment response of the patient with mild cognitive impairment.

[0030] In order to achieve the above-described object, the present invention provides a device for providing gamma brainwave entrainment for a patient with mild cognitive impairment, comprising: a light irradiation unit for providing a visual stimulus to a subject by irradiating a flashing light with a frequency of the gamma band; an brainwave measurement unit for measuring gamma band brainwaves induced in the brain of a subject while the visual stimulus is provided to the subject through the light irradiation unit; and a control unit for selecting a center frequency at which the gamma band brainwave entrainment is most strongly shown as an optimal frequency and controlling the light irradiation unit to provide a visual stimulus to the subject at the selected optimal frequency.

[0031] In addition, in the device for providing gamma brainwave entrainment for a patient with mild cognitive impairment according to the present invention, the control unit controls the light irradiation unit to irradiate flashing lights with different center frequencies in the gamma band to provide a visual stimulus to the subject, and selects a center frequency at which gamma band brainwave entrainment appears most strongly among a plurality of center frequencies based on brain waves measured through the brainwave measurement unit as an optimal frequency, and controls the light irradiation unit to irradiate flashing lights with the selected optimal frequency to provide a visual stimulus to the subject.

[0032] In addition, in a device for providing gamma brainwave tuning for a patient with mild cognitive impairment according to the present invention, the control unit is characterized in that it tracks an optimal frequency that changes over time and controls the light irradiation unit to provide a visual stimulus to the subject using the tracked optimal frequency.

[0033] In addition, in a device for providing gamma brainwave entrainment for a patient with mild cognitive impairment according to the present invention, the control unit provides a visual stimulus to the subject at an optimal frequency at intervals of a preset time, and then controls the light irradiation unit to irradiate flashing lights with different center frequencies again to provide a visual stimulus to the subject, and based on the brainwaves measured again through the brainwave measurement unit, selects a center frequency at which gamma band brainwave entrainment appears most strongly among a plurality of center frequencies as the optimal frequency, and controls the light irradiation unit to irradiate flashing lights with the selected optimal frequency again to provide a visual stimulus to the subject.

[0034] In addition, in the device providing gamma brainwave tuning for a patient with mild cognitive impairment according to the present invention, the optimal frequency is characterized in that it is determined as a frequency having the largest value while the average of the SNR (Signal to Noise Ratio) exceeds a preset value among the optimal frequency candidates determined for each electrode channel by analyzing each brainwave signal acquired for each center frequency through a plurality of electrode channels measuring brainwaves in the occipital lobe region among the brainwave channels and based on the ERSP (Event Related Spectral Perturbation).

[0035] In addition, in the device for providing gamma brainwave tuning for a patient with mild cognitive impairment according to the present invention, the light irradiation unit is implemented in the form of glasses and is characterized in that it irradiates a light that flashes at a frequency in the gamma band through a pair of organic light emitting diodes (OLEDs) mounted in a position where a lens is located, thereby providing a visual stimulus to the subject.

[0036] In addition, in the device for providing gamma brainwave tuning for a patient with mild cognitive impairment according to the present invention, the light irradiation unit is characterized in that it provides a visual stimulus to the subject by irradiating a light that flashes at any one of the center frequencies of 32 Hz, 34 Hz, 36 Hz, 38 Hz, and 40 Hz under the control of the control unit.

[0037] In addition, a method for providing gamma brainwave entrainment for a patient with mild cognitive impairment according to the present invention for achieving the aforementioned purpose is characterized by including the steps of: providing a visual stimulus to a subject by irradiating flashing lights with different center frequencies in the gamma band; measuring gamma band brainwaves induced in the brain of the subject while the visual stimulus is provided to the subject; and selecting a center frequency at which the entrainment of gamma band brainwaves appears most strongly as an optimal frequency, and providing a visual stimulus to the subject at the selected optimal frequency.

[0038] In addition, in the method for providing gamma brainwave entrainment for a patient with mild cognitive impairment according to the present invention, the step of providing a visual stimulus to the subject at the selected optimal frequency is characterized by a step of selecting a center frequency at which gamma band brainwave entrainment appears most strongly among a plurality of center frequencies based on the measured brainwaves as the optimal frequency, and providing a visual stimulus to the subject by irradiating a blinking light at the selected optimal frequency.

[0039] In addition, in a method for providing gamma brainwave entrainment for a patient with mild cognitive impairment according to the present invention, the method further comprises a step of tracking an optimal frequency that changes over time and providing a visual stimulus to the subject using the tracked optimal frequency.

[0040] In addition, in the method for providing gamma brainwave entrainment for a patient with mild cognitive impairment according to the present invention, the step of providing a visual stimulus to the subject using the tracked optimal frequency comprises the steps of: providing the visual stimulus to the subject at the optimal frequency at intervals of a preset period of time, and then re-irradiating a light flickering at a different center frequency to provide the visual stimulus to the subject; re-measuring a gamma band brainwave induced in the brain of the subject while the visual stimulus is provided to the subject; and re-selecting a center frequency at which gamma band brainwave entrainment appears most strongly among a plurality of center frequencies based on the re-measured brainwave as the optimal frequency, and re-irradiating a light flickering at the re-selected optimal frequency to provide the visual stimulus to the subject.

[0041] In addition, in the method for providing gamma brainwave entrainment for a patient with mild cognitive impairment according to the present invention, the optimal frequency is characterized in that it is determined as a frequency having the largest value while the average of the SNR (Signal to Noise Ratio) exceeds a preset value among the optimal frequency candidates determined for each electrode channel by analyzing each brainwave signal acquired for each center frequency through a plurality of electrode channels measuring brainwaves in the occipital lobe region among the brainwave channels and based on the ERSP (Event Related Spectral Perturbation).

[0042] In addition, in the method for providing gamma brainwave entrainment for a patient with mild cognitive impairment according to the present invention, the step of providing a visual stimulus to a subject by irradiating flashing light with different center frequencies in the gamma band is characterized in that the step of providing a visual stimulus to a subject by irradiating flashing light with a center frequency set among center frequencies of 32 Hz, 34 Hz, 36 Hz, 38 Hz, and 40 Hz is a step.

[0043] Specific details of other embodiments are included in the “Specific Details for Carrying Out the Invention” and the attached “Drawings.”

[0044] The advantages and / or features of the present invention and the methods for achieving them will become clear with reference to the various embodiments described in detail below together with the accompanying drawings.

[0045] However, the present invention is not limited to the configuration of each embodiment disclosed below, but may be implemented in various different forms, and each embodiment disclosed in this specification is provided only to ensure that the disclosure of the present invention is complete and to fully inform a person having ordinary skill in the art to which the present invention pertains of the scope of the present invention, and it should be understood that the present invention is defined only by the scope of each claim of the claims.

[0046] According to the present invention, among a plurality of center frequencies, the center frequency at which brainwave synchronization is strongest in a subject is selected as the optimal frequency, and by using the selected optimal frequency, the gamma band brainwaves of the subject are activated, thereby maximizing the treatment response of patients with mild cognitive impairment or Alzheimer's disease using gamma band brainwaves.

[0047] FIG. 1 is a schematic diagram showing the configuration of a device that provides gamma brainwave tuning for a patient with mild cognitive impairment according to one embodiment of the present invention.

[0048] FIG. 2 is a processing diagram illustrating a method for providing gamma brainwave entrainment for a patient with mild cognitive impairment according to one embodiment of the present invention.

[0049] Figure 3 is a schematic diagram showing the characteristics of the participants who participated in this experiment.

[0050] Figure 4 is a diagram showing the distribution of flicker frequencies between the center frequency and non-center frequency shown in this experiment.

[0051] Figure 5 is a schematic diagram showing the effects of flickering frequency on the spread, strength, and stability of gamma connectivity, classified as gamma connectivity areas and event-related spectral perturbations (ERSPs) of tuned gamma-band EEG according to this experiment.

[0052] Figure 6 is a diagram showing the spread of gamma connectivity that appears while presenting a flashing light stimulus according to this experiment.

[0053] Figure 7 is a diagram showing the strength of gamma connectivity that appears while presenting a flashing light stimulus according to this experiment.

[0054] Figure 8 is a diagram showing the stability of gamma connectivity that appears while providing a flashing light stimulus according to this experiment.

[0055] Before describing the present invention in detail, it should be understood that the terms or words used in this specification should not be interpreted as being unconditionally limited to their usual or dictionary meanings, and that the inventor of the present invention may appropriately define and use the concepts of various terms in order to explain his or her invention in the best possible manner, and further, that these terms or words should be interpreted as meanings and concepts that are consistent with the technical idea of ​​the present invention.

[0056] That is, it should be noted that the terms used in this specification are only used to describe preferred embodiments of the present invention, and are not intended to specifically limit the contents of the present invention, and that these terms are defined in consideration of various possibilities of the present invention.

[0057] Additionally, in this specification, it should be noted that singular expressions may include plural expressions unless the context clearly indicates a different meaning, and similarly, even if expressed in plural, may include a singular meaning.

[0058] Throughout this specification, whenever a component is described as "including" another component, it may mean that the component may further include any other component, rather than excluding any other component, unless specifically stated otherwise.

[0059] Furthermore, when it is described that a component is "located within, connected to, or installed within" another component, it should be understood that the component may be installed in direct connection with or in contact with the other component, may be installed spaced apart from the other component by a certain distance, and if it is installed spaced apart from the other component by a certain distance, there may be a third component or means for fixing or connecting the component to the other component, and the description of this third component or means may be omitted.

[0060] On the other hand, if a component is described as being "directly connected" or "directly connected" to another component, it should be understood that no third component or means exists.

[0061] Likewise, other expressions that describe the relationship between components, such as "between" and "directly between", or "adjacent to" and "directly adjacent to", should be interpreted as having the same meaning.

[0062] In addition, it should be noted that the terms “one side,” “the other side,” “one side,” “the other side,” “first,” “second,” etc. in this specification, if used, are used to clearly distinguish one component from another component, and the meaning of the component is not limited by such terms.

[0063] In addition, terms related to position, such as “upper,” “lower,” “left,” and “right,” etc., in this specification, if used, should be understood to indicate relative positions of the corresponding components in the corresponding drawings, and unless absolute positions are specified for these positions, these position-related terms should not be understood to refer to absolute positions.

[0064] Moreover, in the specification of the present invention, it should be noted that the terms “part”, “device”, “module”, “device”, etc., if used, mean a unit capable of processing one or more functions or operations, which may be implemented by hardware or software, or a combination of hardware and software.

[0065] In addition, in this specification, when specifying the drawing numbers for each component of each drawing, the same component has the same drawing number even if the component is shown in a different drawing, that is, the same reference number indicates the same component throughout the specification.

[0066] In the drawings attached to this specification, the size, position, connection relationship, etc. of each component constituting the present invention may be described with some exaggeration, reduction, or omission in order to sufficiently clearly convey the idea of ​​the present invention or for convenience of explanation, and therefore the proportions or scales may not be strict.

[0067] In addition, in the following description of the present invention, a detailed description of a configuration that is judged to unnecessarily obscure the gist of the present invention, for example, a known technology including a prior art, may be omitted.

[0068]

[0069] Hereinafter, with reference to the attached drawings, a device and method for providing gamma brainwave entrainment for a patient with mild cognitive impairment according to a preferred embodiment of the present invention will be described in detail.

[0070] FIG. 1 is a schematic diagram showing the configuration of a device that provides gamma brainwave tuning for a patient with mild cognitive impairment according to one embodiment of the present invention.

[0071] As shown in Fig. 1, a device (100) for providing gamma brain wave tuning for a patient with mild cognitive impairment according to one embodiment of the present invention may include a light irradiation unit (110), a brain wave measurement unit (120), a control unit (130), etc.

[0072] The light irradiation unit (110) can provide a visual stimulus to a subject by irradiating light that flashes at a frequency in the gamma band under the control of the control unit (130).

[0073] The light irradiation unit (110) can be implemented in the form of glasses, and can provide visual stimulation to a subject by injecting flickering light at a frequency in the gamma band through a pair of light emitting diodes (LED) or organic light emitting diodes (OLED) mounted in the position where the lens is located.

[0074] The light irradiation unit (110) can provide a visual stimulus to a subject by irradiating a blinking light with a center frequency (CF) of, for example, 32 Hz, 34 Hz, 36 Hz, 38 Hz, and 40 Hz under the control of the control unit (130).

[0075] As described above, the light irradiation unit (110) provides the subject with a flickering light stimulus (FLS) at one of the center frequencies of 32 Hz, 34 Hz, 36 Hz, 38 Hz, and 40 Hz.

[0076] The flashing light presented to the subject reaches the visual cortex of the brain, stimulating the brain area that processes visual information, causing the brain to tune to that frequency and induce gamma brain waves of that frequency.

[0077] For example, when a subject is provided with a light stimulus (FLS) that flashes at 32 Hz, the subject's brain is tuned to 32 Hz, inducing gamma brain waves of 32 Hz. When a subject is provided with a light stimulus (FLS) that flashes at 36 Hz, the subject's brain is tuned to 36 Hz, inducing gamma brain waves of 36 Hz.

[0078] The intensity of the flickering light stimulus (FLS) provided to the subject through the light irradiation unit (110) can be controlled by modulating the supply voltage applied to the LED or OLED.

[0079] The light irradiation unit (110) can provide a flickering light stimulus (FLS) to a subject at any one of the center frequencies of 32 Hz, 34 Hz, 36 Hz, 38 Hz, and 40 Hz for a set period of time (e.g., 30 minutes) under the control of the control unit (130).

[0080] The light irradiation unit (110) can be connected to the control unit (130) by wire or wirelessly to receive control signals necessary for operation.

[0081] In the embodiment of the present invention, the light irradiation unit (110) is implemented to automatically adjust the frequency and intensity of the flickering light stimulus (FLS) provided to the subject under the control of the control unit (130), but this may also be implemented to be adjusted by the operation of a user (e.g., medical staff).

[0082] The brain wave measurement unit (120) can measure gamma band brain waves induced in the brain of a subject while a visual stimulus is provided to the subject through the light irradiation unit (110).

[0083] In an embodiment of the present invention, the brain wave measurement unit (120) can be implemented as EEG (Electroencephalography).

[0084] Specifically, the brain wave measurement unit (120) can collect brain wave signals in real time through 32 or 64 electrodes while a flashing light stimulus (FLS) is provided at any one of the center frequencies of 32 Hz, 34 Hz, 36 Hz, 38 Hz, and 40 Hz, and record the collected signals in a predetermined memory area.

[0085] In addition, the brainwave measurement unit (120) can visualize the collected signals in graphs and diagrams to easily identify changes over time.

[0086] The brain wave measurement unit (120) can observe and analyze in real time the effect of visual stimulation provided to the subject at center frequencies of 32 Hz, 34 Hz, 36 Hz, 38 Hz, and 40 Hz on the electrical activity of the brain.

[0087] The brain wave measurement unit (120) can provide brain wave signals collected by center frequency to the control unit (130).

[0088] Additionally, the brainwave measurement unit (120) can provide analysis results by center frequency to the control unit (130).

[0089] The control unit (130) analyzes the brain waves measured through the brain wave measurement unit (120) to select the center frequency at which the synchronization of gamma band brain waves is most strongly shown as the optimal frequency, and can control the light irradiation unit (110) to provide visual stimulation to the subject at the selected optimal frequency.

[0090] The control unit (130) can select the center frequency at which the gamma band brain wave synchronization is most strongly displayed as the optimal frequency among the center frequencies of 32 Hz, 34 Hz, 36 Hz, 38 Hz, and 40 Hz based on the brain wave signals collected by center frequency provided by the brain wave measurement unit (120).

[0091] Here, the optimal frequency at which the gamma band brainwave synchronization is most strongly observed among the center frequencies of 32 Hz, 34 Hz, 36 Hz, 38 Hz, and 40 Hz can be selected based on Event Related Spectral Perturbation (ERSP).

[0092] Specifically, each brain wave signal acquired by center frequency through multiple electrode channels (e.g., O1, O2, Oz, POz, Pz) that measure brain waves in the occipital lobe region among brain wave channels is analyzed, and the center frequencies are ranked by electrode channel based on ERSP, and the average ranking of multiple electrode channels by center frequency is calculated.

[0093] The center frequency with the highest average rank can be determined as the optimal frequency. In this case, if two or more frequencies have the same average rank, the center frequency with the highest absolute value of ERSP in any of the multiple electrode channels can be determined as the optimal frequency.

[0094] In addition, among the EEG channels, the EEG signals obtained by center frequency through multiple electrode channels (e.g., O1, O2, Oz, POz, Pz) for measuring EEG in the occipital lobe region are analyzed, and the largest ERSPs among the ERSPs obtained at each center frequency for each electrode channel are compared with each other, and the center frequency at which the largest ERSP is obtained (any one of 32 Hz, 34 Hz, 36 Hz, 38 Hz, and 40 Hz) is determined as an optimal frequency candidate, and among the optimal frequency candidates determined for each electrode channel, a frequency at which the average of the SNR (Signal to Noise Ratio) of the electrode channels exceeds a preset value (e.g., 1.5) and the SNR has the largest value can be determined as the optimal frequency. At this time, if there is no frequency among the optimal frequency candidates whose average SNR exceeds a preset value, the subject is judged to have a SSVEP (Steady-State Visual Evoked Potential) deficit, which is an abnormal or weak brain response to visual stimulation, and the subject can be excluded from treatment that promotes activity in the gamma frequency band of the brain by activating gamma band brain waves through visual stimulation.

[0095] As described above, the control unit (130) can control the light irradiation unit (110) to irradiate a light that blinks at any one of the center frequencies of 32 Hz, 34 Hz, 36 Hz, 38 Hz, and 40 Hz for a set period of time to select an optimal frequency among different center frequencies of the gamma band, for example, 32 Hz, 34 Hz, 36 Hz, 38 Hz, and 40 Hz, thereby providing a visual stimulus to the subject. At this time, the control unit (130) can control the light irradiation unit (110) to provide the subject with a light stimulus that blinks at 32 Hz, a light stimulus that blinks at 34 Hz, a light stimulus that blinks at 36 Hz, a light stimulus that blinks at 38 Hz, and a light stimulus that blinks at 40 Hz, respectively.

[0096] In addition, the control unit (130) may select a center frequency at which gamma band brainwave synchronization is most strongly displayed among a plurality of center frequencies (e.g., 32 Hz, 34 Hz, 36 Hz, 38 Hz, 40 Hz) based on the brainwaves measured through the brainwave measurement unit (120) as the optimal frequency, and control the light irradiation unit (110) to provide a visual stimulus to the subject by irradiating a blinking light at the selected optimal frequency. Here, the optimal frequency selected for each subject may be different. For example, the optimal frequency for subject A may be selected as 38 Hz, the optimal frequency for subject B may be selected as 36 Hz, and the optimal frequency for subject C may be selected as 40 Hz.

[0097] As described above, once the optimal frequency is selected, the selected optimal frequency can be used to provide the subject with a flashing light stimulus at the optimal frequency to activate the subject's gamma band brain waves, thereby maximizing the therapeutic response.

[0098] At this time, the treatment response may weaken due to tolerance as visual stimulation therapy using the optimal frequency is repeated.

[0099] Accordingly, in another embodiment of the present invention, the optimal frequency that changes over time is tracked, and a light stimulus that flashes at the tracked optimal frequency is provided to the subject to maximize the therapeutic response.

[0100] That is, the control unit (130) can track the optimal frequency that changes with time and control the light irradiation unit (110) to provide visual stimulation to the subject using the tracked optimal frequency.

[0101] Specifically, the control unit (130) provides a visual stimulus to the subject at an optimal frequency selected at intervals for a preset period of time, and then controls the light irradiation unit (110) to irradiate a flashing light again at one of different center frequencies of the gamma band, for example, 32 Hz, 34 Hz, 36 Hz, 38 Hz, and 40 Hz, to provide a visual stimulus to the subject, and based on the brain waves measured again through the brain wave measurement unit (120), the center frequency at which the brain wave synchronization of the gamma band appears the strongest among a plurality of center frequencies is selected as the optimal frequency again, and the light irradiation unit (110) can be controlled to irradiate a flashing light at the optimal frequency selected again to provide a visual stimulus to the subject.

[0102] To explain this with an example, the control unit (130) controls the light irradiation unit (110) to provide the subject with a light stimulus that flickers at 32 Hz, a light stimulus that flickers at 34 Hz, a light stimulus that flickers at 36 Hz, a light stimulus that flickers at 38 Hz, and a light stimulus that flickers at 40 Hz, while measuring brain waves through the brain wave measurement unit (120), and analyzing the brain waves measured while providing the flickering light stimulus to the subject to select the optimal frequency. In the case where the selected optimal frequency is 34 Hz, a light stimulus flickering at 34 Hz ​​is provided to the subject for a set time (e.g., 30 minutes) at intervals (e.g., morning and evening) for a preset period (e.g., 2 weeks), and then a light stimulus flickering at 32 Hz, a light stimulus flickering at 34 Hz, a light stimulus flickering at 36 Hz, a light stimulus flickering at 38 Hz, and a light stimulus flickering at 40 Hz are respectively provided to the subject, while the brain waves are measured again through the brainwave measurement unit (120), and the brain waves measured while the blinking light stimulus is provided to the subject are analyzed to select the optimal frequency again. At this time, in the case where the selected optimal frequency is 36 Hz, the light irradiation unit (110) can be controlled to provide the subject with a light stimulus flickering at the selected optimal frequency of 36 Hz.

[0103] In the embodiment of the present invention, the control unit (130) is implemented to analyze brain waves measured through the brain wave measurement unit (120) to select an optimal frequency, but it may also be implemented to select the brain wave measurement unit (120) and have the brain wave measurement unit (120) provide information on the selected optimal frequency to the control unit (130), or have the user input information on the selected optimal frequency to the control unit (130).

[0104] FIG. 2 is a processing diagram illustrating a method for providing gamma brainwave entrainment for a patient with mild cognitive impairment according to one embodiment of the present invention.

[0105] The method for providing gamma brainwave entrainment for a patient with mild cognitive impairment according to the present invention can be performed on a configuration substantially identical to that of the device (100) for providing gamma brainwave entrainment for a patient with mild cognitive impairment illustrated in FIG. 1.

[0106] First, in step S10, a visual stimulus can be provided to the subject by flashing light with different center frequencies in the gamma band.

[0107] Specifically, in the above-mentioned step S10, for example, a light stimulus flashing at 32 Hz, a light stimulus flashing at 34 Hz, a light stimulus flashing at 36 Hz, a light stimulus flashing at 38 Hz, and a light stimulus flashing at 40 Hz can be provided to the subject at time intervals.

[0108] While a visual stimulus is provided to the subject through the above-described step S10, the gamma band brain waves induced in the subject's brain can be measured in step S20.

[0109] Specifically, while the light stimulus flashing at 32 Hz, the light stimulus flashing at 34 Hz, the light stimulus flashing at 36 Hz, the light stimulus flashing at 38 Hz, and the light stimulus flashing at 40 Hz are respectively provided in step S10, brain wave signals can be collected in real time through 32 or 64 electrode channels in step S20, and the collected signals can be recorded in a predetermined memory area.

[0110] Thereafter, in step S30, the brain waves measured through the above-described step S20 are analyzed to select the center frequency at which the synchronization of gamma band brain waves is most strongly shown as the optimal frequency, and a visual stimulus can be provided to the subject at the selected optimal frequency.

[0111] Specifically, in the above step S30, based on the brain wave signals collected by center frequency through the above step S20, the center frequency at which the gamma band brain wave synchronization appears most strongly among the center frequencies of 32 Hz, 34 Hz, 36 Hz, 38 Hz, and 40 Hz can be selected as the optimal frequency.

[0112] In the above step S30, for example, each brain wave signal acquired by center frequency through a plurality of electrode channels (e.g., O1, O2, Oz, POz, Pz) for measuring brain waves in the occipital lobe region among brain wave channels is analyzed, and the center frequencies are ranked by electrode channel based on ERSP, and the average ranking of the plurality of electrode channels by center frequency is calculated.

[0113] The center frequency with the highest average rank can be determined as the optimal frequency. In this case, if two or more frequencies have the same average rank, the center frequency with the highest absolute value of ERSP in any of the multiple electrode channels can be determined as the optimal frequency.

[0114] As another example, among the EEG channels, the EEG signals obtained by center frequency through a plurality of electrode channels (e.g., O1, O2, Oz, POz, Pz) that measure EEG in the occipital lobe region are analyzed, and the largest ERSPs among the ERSPs obtained at each center frequency for each electrode channel are compared with each other, and the center frequency at which the largest ERSP is obtained (any one of 32 Hz, 34 Hz, 36 Hz, 38 Hz, and 40 Hz) is determined as an optimal frequency candidate, and among the optimal frequency candidates determined for each electrode channel, a frequency at which the average of the SNR (Signal to Noise Ratio) of the electrode channels exceeds a preset value (e.g., 1.5) and the SNR has the largest value can be determined as the optimal frequency.

[0115] As described above, after selecting the optimal frequency at which the gamma band brainwave entrainment is most strongly exhibited among multiple center frequencies (e.g., 32 Hz, 34 Hz, 36 Hz, 38 Hz, 40 Hz), a visual stimulus can be provided to the subject by irradiating a flashing light at the selected optimal frequency.

[0116] In one embodiment of the present invention, by using the optimal frequency selected through the above-described step S30, a light stimulus that flashes at the optimal frequency is provided to the subject, thereby activating the subject's gamma band brain waves, thereby maximizing the therapeutic response.

[0117] In addition, in another embodiment of the present invention, an optimal frequency that changes over time can be tracked, and a visual stimulus can be provided to a subject using the tracked optimal frequency.

[0118] That is, in step S40, the optimal frequency that changes over time can be tracked, and a visual stimulus can be provided to the subject using the tracked optimal frequency.

[0119] Specifically, after providing a visual stimulus to the subject at the optimal frequency selected in step S30 described above at intervals for a preset period of time, the visual stimulus can be provided to the subject again by irradiating flashing light at different center frequencies in the gamma band in step S40 described above.

[0120] And while the visual stimulus is provided to the subject, the gamma band brain waves induced in the subject's brain can be measured again.

[0121] And then, based on the measured brain waves, the center frequency at which the brain wave synchronization in the gamma band is most strongly shown among multiple center frequencies is selected as the optimal frequency, and a flashing light is irradiated at the selected optimal frequency to provide visual stimulation to the subject.

[0122] The method according to the embodiment described above and the operation by the device performing the same can be implemented at least partially as a computer program and stored in a computer-readable recording medium.

[0123] For example, it may be implemented with a program product comprising a computer-readable medium containing program code, which may be executed by a processor to perform any or all of the steps, operations, or processes described.

[0124] The computer may be any computing device, such as a desktop computer, laptop computer, notebook computer, smartphone, or the like, or may be integrated into any such device. The computer is a device having one or more alternative and special purpose processors, memory, storage space, and networking components (either wireless or wired). The computer may run an operating system, such as, for example, an operating system compatible with Microsoft's Windows, Apple's OS X or iOS, a Linux distribution, or Google's Android OS.

[0125] The computer-readable recording medium includes all types of recording identification devices that store data that can be read by a computer. Examples of the computer-readable recording medium include ROM, RAM, CD-ROM, magnetic tape, floppy disk, optical data storage identification devices, etc. In addition, the computer-readable recording medium may be distributed across network-connected computer systems, so that computer-readable codes can be stored and executed in a distributed manner. In addition, functional programs, codes, and code segments for implementing the present embodiment will be readily understood by those skilled in the art to which the present embodiment pertains.

[0126] In this way, according to the present invention, among a plurality of center frequencies, the center frequency at which brainwave synchronization is most strongly shown in the subject is selected as the optimal frequency, and by using the selected optimal frequency, the gamma band brainwaves of the subject are activated, thereby maximizing the treatment response of patients with mild cognitive impairment or Alzheimer's disease using gamma band brainwaves.

[0127] Additionally, since it is possible to provide a flickering light stimulus (FLS) to a subject using safe visible light, it is possible to induce gamma-band brain waves by providing a flickering light stimulus to a subject at low cost.

[0128]

[0129] [Experimental Example]

[0130] target

[0131] This experiment was conducted to verify whether visual stimulation using a central frequency selected for each subject induces gamma-band brain waves better than visual stimulation using other frequencies.

[0132] method

[0133] Gamma-band EEG was synchronised in 32 cognitively normal elderly participants using flashing lights at 32 Hz, 34 Hz, 36 Hz, 38 Hz and 40 Hz.

[0134] Among the frequencies of 32 Hz, 34 Hz, 36 Hz, 38 Hz, and 40 Hz, the central frequency was selected for each subject, and the spread, strength, and stability of the gamma connectivity induced by the flashing light stimulus at the central frequency for each subject were compared with those at other frequencies using the Generalized Estimating Equation (GEE) and repeated measures Analysis of Variance (ANOVA).

[0135] result

[0136] In approximately two-thirds of the participants, 32 Hz (40.6%) and 34 Hz ​​(28.1%) were selected as the center frequencies.

[0137] Gamma connectivity involving the visual cortex (GC V-NV ) average spread, strength, and stability of gamma connectivity (GC) not involving visual cortex NV-NV , p<0.05).

[0138] Between the visual cortex and other brain regions, light stimuli flashing at a central frequency induce broader, stronger, and more stable gamma connectivity than other frequencies (p<0.004 for spread and intensity, p=0.00y for stability).

[0139] conclusion

[0140] Gamma-band brain waves induced by visual stimuli can spread better to other brain regions when their frequency matches the subject's selected center frequency.

[0141]

[0142] According to this experiment, the center frequency of the subject (elderly person) is different for each person, and it can be confirmed that the gamma-band brain waves induced in the visual cortex by visual stimulation tuned to the individual's center frequency are best spread to other target brain regions.

[0143] introduction

[0144] In Alzheimer's disease, gamma-band brain waves associated with many cognitive processes are abnormal. The intensity of resting-state gamma-band brain waves begins to decline early in the disease, and this decline is closely related to the severity of Alzheimer's-related pathology and cognitive impairment. Moreover, gamma-band brain wave responses are not only delayed, but also their intensity and connectivity are reduced.

[0145] The center frequency is the frequency at which ERSP shows the most significant change in response to external visual stimuli, and the center frequency decreases with age as the contrast sensitivity and excitability of GABAergic inhibitory interneurons decrease, but the speed of this change may not be uniform across individuals, so the center frequency may vary across subjects (elderly people).

[0146] Furthermore, although sensory stimulation with a frequency that matches an individual's center frequency (CF) can induce stronger gamma-band brain waves in the sensory cortex, it is not known whether gamma-band brain waves induced by sensory stimulation with a frequency that matches an individual's center frequency can propagate better from the sensory cortex to other target brain regions than those induced by sensory stimulation with a different non-center frequency (NCF).

[0147] In this experiment, we compare the spread, strength, and stability of gamma connectivity induced by flashing light stimuli to investigate whether gamma-band EEG induced by visual stimuli flashing at a central frequency (CF) can propagate better from the visual cortex to other brain regions than gamma-band EEG induced by visual stimuli flashing at a different non-central frequency (NCF).

[0148] 1) When gamma-band brain waves induced by a flashing light stimulus propagate from the visual cortex to other brain regions, gamma connectivity (GC) involving the visual cortex after the flashing light stimulus V-NV ) Gamma connectivity (GC) that does not involve the visual cortex NV-NV , p<0.05), and 2) if the gamma-band EEG elicited by the light stimulus flashing at the center frequency propagates better than the gamma-band EEG elicited by the light stimulus flashing at a non-center frequency, then gamma connectivity (GC) involving the visual cortex elicited by the light stimulus flashing at the center frequency V-NV ) can be greater than those induced by light stimuli flashing at non-central frequencies.

[0149] method

[0150] participant

[0151] As shown in Figure 3 , 44 cognitively normal volunteers aged 60 years or older (21 men, 23 women; mean age, 69.9 ± 2.3 years) were enrolled as participants. Geriatric psychiatrists administered a standardized diagnostic interview, physical and neurological examinations, and laboratory tests using the Alzheimer's Disease Assessment Packet Registry Consortium and the Korean version of the Mini-International Neuropsychiatric Interview.

[0152] "Cognitively normal" was defined as a standard deviation of -1.5 or more and a clinical dementia rating of 0 on all neuropsychological tests, based on age, sex, and education standards for Korean older adults. All participants were normal or had corrected-to-normal vision and no hearing impairment. No one had a history of major psychiatric or neurological disorders.

[0153] Of the 44 participants, 3 withdrew consent, 8 had excessive electromyographic (EMG) noise on their EEG, and 1 was excluded from the study due to missing EEG digital data; the remaining 32 were included in the final analysis.

[0154] Administration of flashing light stimulation (FLS)

[0155] In this experiment, a pair of white organic light-emitting diode (OLED) panels (4.7 cm × 4.7 cm, color temperature 3000 K) attached to glasses were used to present each participant with a flickering light stimulus. The voltage-luminance characteristics of the OLED panels were measured using a spectroradiometer calibrated in voltage-controlled mode using a precision source-measure unit.

[0156] The intensity and frequency of the flashing light stimulus were changed by modulating the amplitude and frequency of the square rhythm, and the intensity of the flashing light stimulus was changed by modulating the supply voltage of the OLED. In this experiment, five different flashing frequencies (32 Hz, 34 Hz, 36 Hz, 38 Hz, and 40 Hz) were used.

[0157] Because previous studies have shown that a 700 cd / m2 white flickering light stimulus induces the strongest gamma-band EEG in the visual cortex of older adults, this experiment uses only the ERSP and gamma connectivity induced by a 700 cd / m2 white flickering light stimulus at five flicker frequencies (32 Hz, 34 Hz, 36 Hz, 38 Hz, and 40 Hz) for analysis.

[0158] MRI acquisition and preprocessing

[0159] All participants underwent brain MRI, and three-dimensional T1-weighted MR images were acquired in Digital Imaging and Communications in Medicine (DICOM) format using the following protocol.

[0160] Repetition time / echo time=8.2㎳ / 4.6㎳, acquisition matrix=175×240×240, voxel size=1.0×0.5×0.5㎣, slice thickness=1㎜, flip angle=8°.

[0161] And the DICOM format image is converted to NIFTI (Neuroimaging Informatics Technology Initiative) format.

[0162] Images in NIFTI format are re-segmented into 1×1×1㎣ isotropic voxels, and the entire brain structure is automatically segmented.

[0163] Electroencephalogram (EEG) recording and preprocessing

[0164] Electroencephalography (EEG) is recorded using 64 silver-AgCl electrodes placed on an elastic cap according to the extended international 10-20 system. FCz serves as the reference electrode, the forehead serves as the ground electrode, and a pair of electrodes are placed above and below the left eye to record electromyography (EMG).

[0165] Electrode impedance is maintained below 10 kΩ during recording, and a 24-bit DC amplifier and BrainVision Recorder amplify and store the recorded EEG signals.

[0166] The sampling rate is 1,000 Hz, and no online filtering is applied to the electroencephalogram (EEG) recordings. Stimulus markers are delivered by a flashing light stimulus (FLS) control system and are synchronized with the resting-state electroencephalogram (rsEEG).

[0167] MATLAB, EEGLAB, and BSMART toolboxes can be used for preprocessing and analysis.

[0168] The recorded signal is filtered with a 1 Hz high-pass finite impulse response filter and a 60 Hz notch filter and then applied to a common average reference.

[0169] Independent component analysis (ICA) is performed to remove eye blinks and other ocular artifacts from electroencephalography (EEG) signals.

[0170] After preprocessing, a 5-minute resting-state electroencephalogram (rsEEG) recording is divided into 500-ms epochs, and 20 artifact-free epochs are randomly selected. By acquiring 4,000-ms epochs starting 1,000 ms before each FLS and ending 1,000 ms after each FLS offset, 20 4,000-ms epochs can be generated for each frequency.

[0171] Each 4,000 ms of electroencephalogram (EEG) data acquired during FLS is segmented into 500 ms time windows with 250 ms overlap, creating 15 consecutive overlapping data segments.

[0172] Among them, seven data segments from the 5th to the 12th segment represent 2,000 ms electroencephalogram (EEG) signals during FLS.

[0173] Individual center frequency identification

[0174] Each participant's center frequency (CF) is identified using the FLS-derived ERSPs of four channels (Oz, POz, O1, O2). For each channel, five flicker frequencies (32 Hz, 34 Hz, 36 Hz, 38 Hz, 40 Hz) are ranked based on their ERSPs, and the average rank of the four channels for each flicker frequency is calculated. The flicker frequency with the highest average rank is defined as the participant's center frequency.

[0175] If two or more frequencies have the same average rank, the flicker frequency with the largest absolute value of ERSP in any of the four channels is defined as the center frequency. The remaining four flicker frequencies, excluding the frequency defined as the center frequency, are defined as NCF1, NCF2, NCF3, and NCF4 according to their ERSP ranks.

[0176] Functional gamma connectivity analysis

[0177] EEG functional connectivity can be measured using the MNE library in Python.

[0178] First, the brain surface is extracted from individual T1-weighted images. A boundary element model (BEM) is then computed, generating a source space. Electrode locations are digitized using the 3D model image and manually positioned using EEGlab. After coregistration between the EEG digitized image and the individual source spaces, forward and backward models are computed.

[0179] Using images from the Human Connectome Project (HCP), 44 different cortices are labeled, 22 in each hemisphere. The visual area is composed of the ventral stream visual cortex, primary visual cortex, early visual cortex, and dorsal stream visual cortex, which are eight cortices in both the left and right hemispheres. These are classified according to their relationship to the corresponding regions. Cortices that appear to overlap with multiple regions are excluded from the visual area. The regional gamma connectivity is assessed using the phase-locked value (PLV) from both rsEEG and EEG acquired during FLS. The total number of possible edges in the PLV matrix is ​​1892. Of these, 576 edges are GC-bound. V-NV , and 1,000 edges are included in the GC NV-NV is included.

[0180] To confirm the gamma connectivity induced by FLS, the PLV of each edge in the seven data segments during FLS was compared with the PLV of rsEEG using a paired t-test with Green-Geisser asphericity correction and Bonferroni post hoc comparisons. Edges that showed significantly higher PLV in any of the seven data segments during FLS compared to rsEEG were marked as E, indicating FLS-induced gamma connectivity. FLS is defined as E FLS During FLS, PLV was significantly stronger than rsEEG for more than 1,000 ms, indicating stable gamma connectivity induced by FLS. FLS is defined as . Then, E for each frequency condition FLS We calculate the spread, stability, and strength of the gamma connectivity to measure how wide the increase in gamma connectivity is, how long the increased gamma connectivity lasts without interruption, and how strong the increase in gamma connectivity is, respectively. The spread is the number of edges E among all possible edges. FLS is defined as the ratio (%) of all E FLS Medium sE FLS is defined as the ratio (%) of all E FLS It is defined as the average PLV of seven data segments during the FLS.

[0181] Statistical analysis

[0182] Continuous and categorical variables are compared between groups using Student's t-test and chi-square test, respectively.

[0183] Differences in CF distributions between five flicker frequencies (32 Hz, 34 Hz, 36 Hz, 38 Hz, and 40 Hz) were investigated using the Friedman rank test with Bonferroni post hoc comparisons. ERSP values ​​were compared between central frequencies (CF) and non-central frequencies (NCF) using repeated-measures analysis of variance (rmANOVA) with Bonferroni post hoc comparisons.

[0184] Gamma connectivity area (GC) v-Nv and GC Nv-Nv ), flicker frequency classified by ERSP of gamma-band EEG induced in the visual cortex (CF, NCF1, NCF2, NCF3, NCF4), E FLS (diffusion) and sE FLS The effect of interactions on (stability) induction is investigated using generalized estimating equations (GEE) with Bonferroni post hoc comparisons.

[0185] Gamma connectivity area (GC) v-Nv and GC Nv-Nv ), flicker frequency classified by ERSP of gamma-band EEG induced in the visual cortex (CF, NCF1, NCF2, NCF3, NCF4), E FLS The effect of interaction on the strength of is investigated using repeated measures analysis of variance (rmANOVA) with Bonferroni post hoc comparisons.

[0186] result

[0187] Demographic and clinical characteristics were similar between participants who entered the trial and those who were excluded (see Figure 3 ).

[0188] As shown in Figure 4, the probability of being identified as a central frequency (CF) is statistically different across the five blink frequencies (p=0.002). Post hoc comparisons revealed that the distribution of blink frequencies identified as central frequencies differed from those identified as non-central frequencies (NCFs) (p=0.013 for NCF1, p=0.013 for NCF2, p=0.005 for NCF3, and p=0.034 for NCF4).

[0189] The flicker frequency of 32 Hz (40.6%) was most commonly identified as the center frequency (CF), followed by 34 Hz ​​(28.1%). However, in approximately one-third of participants, other flicker frequencies were identified as the center frequency.

[0190] Flashing light stimulus at center frequency (FLS) CF) had the highest mean ERSP (10.7±4.4), followed by FLS NCF1 (9.9±4.4), FLS NCF2 (9.1±4.2), FLS NCF3 (7.8±4.0) and FLS NCF4 (7.1±3.9) followed, and the difference was statistically significant (F=74.579, p<0.001).

[0191] As shown in Figure 5, the GEE model includes the gamma connectivity region (GC) for the spread and stability of gamma connectivity. v-Nv and GC Nv-Nv ) and blink frequency classified by ERSP (CF, NCF1, NCF2, NCF3, and NCF4) are all significant main effects (for gamma connectivity area W=62.548, p<0.001; for blink frequency W=52.339, p<0.001). The interaction between them shows marginal statistical significance (W=9.444, p=0.051). GC v-Nv The average prevalence (18.9±31.1%) of GC Nv-Nv is approximately 1.6 times higher than the average diffusion (10.8±31.1%) of GC v-Nv Wow GC Nv-Nv As a result of separate analysis, GC v-Nv (W=620.237, p<0.001) and GC Nv-Nv (W=1617.402, p=0.016) There is a significant difference in the spread between CF and NCF. GC v-Nv FLS in CF and FLS NCF1 Diffusion induced by FLS NCF3 and FLS NCF4 is significantly higher than the diffusion induced by GC (p<0.001). However, GC Nv-Nv FLS in CF The diffusion induced by is similar to the diffusion induced by FLS in NCF (p>0.05).

[0192] These results suggest that gamma-band EEG induced in the visual cortex by FLS of CF or NCF1 may be more extensive than gamma-band EEG induced by FLS of other NCFs (see Fig. 6).

[0193] The main effects of gamma connectivity area, blink frequency classified by ERSP, and the interaction for gamma connectivity strength were all significant in repeated measures analysis of variance (rmANOVA) (for gamma connectivity area, F1,1=99.320, p<0.001; for blink frequency, F1,4=234.399, p<0.001; for the interaction, F1,4=84.718, p<0.001; see Figure 5).

[0194] GC v-Nv The average intensity (0.22±0.03) of GC Nv-Nv It is about 1.15 times higher than the average intensity (0.19±0.02) of GC v-Nv Wow GC Nv-Nv As a result of separate analysis, the intensity induced by FLS was GC v-Nv (F4, 124=241.221, p<0.001) and GC Nv-Nv (F4, 124=109.125, p<0.001) There was a significant difference between the blink frequencies in all cases. Post hoc comparisons showed that FLS CF The intensity induced by GC v-Nv FLS in NCF2 , FLS NCF3 and FLS NCF4 Significantly higher than the intensity induced by GC (p<0.001) Nv-Nv FLS in NCF3 and FLS NCF4 Significantly higher than the intensity induced by FLS NCF1 and FLS NCF2 is significantly lower than the intensity induced by (p<0.001).

[0195] These results suggest that when the flickering frequency of FLS matches the individual center frequency, gamma-band EEG in other brain regions may be more closely phase-locked to the gamma EEG induced by FLS in the visual cortex than when it is not (see Figure 7).

[0196] The main effects of gamma connectivity regions and flicker frequency classified by ERSP on gamma connectivity stability were also significant in the GEE model (for gamma connectivity regions, W=7.518, p=0.007; for flicker frequency, W=15.476, p=0.004). However, their interaction was not statistically significant (W=2.296, p=0.681; see Figure 5 ).

[0197] GC v-Nv The average stability (23.2±42.2%) of GC Nv-Nv It is about 1.5 times higher than the average stability (16.0±37.7%).

[0198] As shown in Fig. 8, when the frequency of FLS is the center frequency (CF), GC v-Nv It has the highest stability (130 GC) v-Nv E FLS 40 sE FLS [30.8%]), GC Nv-Nv Second highest in (112 GC) NV-Nv sE FLS 22 sE FLS [19.6%]). GC v-Nv Wow GC Nv-Nv As a result of separate analysis, GC v-Nv In FLS CF Wow FLS NCF The stability between the two was significantly different (W=11.938, p=0.018), and the post-hoc comparison showed that FLS CF The stability induced by GC v-Nv FLS in NCF3 is significantly higher than the stability induced by GC (p=0.012). However, GC Nv-NvIn , the diffusion induced by FLS did not differ between blink frequencies (W=6.542, p=0.162).

[0199] These results are FLS CF Gamma-band EEG induced in the visual cortex by FLS NCF This suggests that gamma-band EEG induced by the brain can spread to other brain regions for a longer period of time.

[0200] argument

[0201] This experiment confirmed that the center frequency (CF) varied among older participants, and that flashing light stimuli (FLS) at an individual's center frequency (CF) increased gamma connectivity between the visual cortex and other brain regions more broadly, more strongly, and more reliably than flashing light stimuli at other frequencies. This suggests that the flashing frequency of FLS for gamma entrainment intervention in Alzheimer's disease patients needs to be individualized based on the individual's center frequency (CF).

[0202] To date, five clinical trials involving small groups of Alzheimer's disease patients have investigated the efficacy of gamma entrainment using daily 40 Hz visual or visual-auditory complex stimulation for 1 to 6 months. Benefits such as delayed brain atrophy, enhanced network connectivity, and improved cognitive or daily function were found in four studies. However, amyloid beta (Aβ) reduction was not assessed in three trials, and was not observed in two trials. These findings highlight the need for further research to fine-tune stimulation parameters for effective gamma entrainment in Alzheimer's disease patients.

[0203] In this experiment, we use PLV to measure the phase synchronization of gamma-band EEG signals in two different regions. A higher PLV indicates stronger synchronization between the two EEG signals. In this experiment, gamma connectivity significantly increased after FLS, and GC v-NvGC in Nv-Nv Compared to GC, the increase is wider, stronger, and more stable. v-Nv GC in Nv-Nv A greater increase compared to GC is that the gamma band brain waves contained in the visual cortex propagate to other brain regions. v-Nv This may at least partially reflect the fact that it may contribute to the increase of .

[0204] In addition, in this experiment, GC v-Nv In Alzheimer's disease, the increase in FLS is broader and stronger when FLS is flickered at the individual's center frequency (CF) than at other frequencies. In Alzheimer's disease, both the strength of gamma brain waves and functional connectivity are reduced across multiple brain regions. Furthermore, memory is associated with functional gamma connectivity. Therefore, stronger and more widespread interventions of gamma brain waves may be more effective as therapeutic interventions in Alzheimer's disease. This suggests that adapting the flicker frequency of FLS to the individual's center frequency (CF) may be necessary to achieve stronger entrainment and a wider spread of gamma-band EEG to enhance the effectiveness of gamma entrainment in Alzheimer's disease patients.

[0205] This experiment demonstrated that when the frequency of FLS matches the individual's center frequency (CF), gamma-band brain waves tuned by FLS can spread better to other brain regions.

[0206] conclusion

[0207] This experiment illuminates the optimal conditions for FLS to effectively induce gamma functional connectivity in individual humans. Previous FLS studies have focused on specific gamma frequencies to produce strong entrainment. While the general range of 32–38 Hz is effective in inducing gamma-band EEG connectivity, adjusting FLS based on center frequency (CF) to accommodate individual differences offers benefits beyond strong entrainment. This experiment demonstrated that center frequency (CF) varies across individuals, and that a flashing light stimulus (FLS) at the center frequency CF ) suggests that it triggers significant changes in areas interconnected with the visual area. Moreover, FLS CF This means that not only does it result in stronger gamma-band brainwave entrainment, but it also results in wider, stronger, and more stable synchronization across the brain during the stimulation period.

[0208]

[0209] Above, although some examples have been given and various preferred embodiments of the present invention have been described, the description of the various embodiments described in the “Specific Details for Carrying Out the Invention” section is merely exemplary, and those skilled in the art to which the present invention pertains will readily understand that they can carry out various modifications of the present invention or carry out equivalent implementations of the present invention based on the above description.

[0210] In addition, since the present invention can be implemented in various other forms, the present invention is not limited by the above description, and the above description is provided only to make the disclosure of the present invention complete and to fully inform a person having ordinary skill in the art to which the present invention belongs of the scope of the present invention, and it should be understood that the present invention is defined only by each claim of the claims.

[0211] [Explanation of symbols]

[0212] 110. Light irradiation department,

[0213] 120. EEG measurement unit,

[0214] 130. Control unit

Claims

1. A light irradiation unit that provides visual stimulation to a subject by irradiating light that flashes at a frequency in the gamma band; An electroencephalographic measurement unit that measures gamma band brain waves induced in the brain of a subject while a visual stimulus is provided to the subject through the above light irradiation unit; and A device for providing gamma brainwave entrainment for a patient with mild cognitive impairment, characterized by including a control unit that selects a center frequency at which gamma band brainwave entrainment is most strongly shown as an optimal frequency and controls the light irradiation unit to provide a visual stimulus to a subject at the selected optimal frequency.

2. In paragraph 1, The above control unit, A device for providing gamma brainwave entrainment for a patient with mild cognitive impairment, characterized in that the light irradiation unit is controlled to irradiate flashing lights with different center frequencies in the gamma band to provide visual stimulation to a subject, and the light irradiation unit is controlled to select a center frequency at which gamma band brainwave entrainment is most strongly shown among a plurality of center frequencies based on brain waves measured through the brainwave measurement unit as an optimal frequency, and the light irradiation unit is controlled to irradiate flashing lights with the selected optimal frequency to provide visual stimulation to the subject.

3. In paragraph 1, The above control unit, A device for providing gamma brainwave entrainment for patients with mild cognitive impairment, characterized in that it tracks an optimal frequency that changes over time and controls the light irradiation unit to provide visual stimulation to the subject using the tracked optimal frequency.

4. In paragraph 3, The above control unit, A device for providing gamma brainwave entrainment for a patient with mild cognitive impairment, characterized in that after providing a visual stimulus to a subject at an optimal frequency at intervals of a preset time, the light irradiation unit is controlled to irradiate flashing lights with different center frequencies again to provide a visual stimulus to the subject, and based on the brainwaves measured again through the brainwave measurement unit, the center frequency at which brainwave entrainment in the gamma band is most strongly shown among a plurality of center frequencies is selected as the optimal frequency, and the light irradiation unit is controlled to irradiate flashing lights with the selected optimal frequency again to provide a visual stimulus to the subject.

5. In any one of paragraphs 1 to 4, The above optimal frequency is, A device that provides gamma brainwave entrainment for patients with mild cognitive impairment, characterized in that each brainwave signal acquired by center frequency through multiple electrode channels measuring brainwaves in the occipital lobe region among brainwave channels is analyzed, and among the optimal frequency candidates determined for each electrode channel based on ERSP (Event Related Spectral Perturbation), the frequency having the largest value while the average of SNR (Signal to Noise Ratio) exceeds a preset value is determined.

6. In paragraph 1, The above light irradiation unit, A device that provides gamma brainwave entrainment for patients with mild cognitive impairment, characterized in that it is implemented in the form of glasses and provides visual stimulation to the subject by irradiating light that flashes at a frequency in the gamma band through a pair of organic light emitting diodes (OLEDs) mounted in the location where the lenses are located.

7. In paragraph 1 or paragraph 6, The above light irradiation unit, A device for providing gamma brainwave entrainment for patients with mild cognitive impairment, characterized in that it provides visual stimulation to a subject by irradiating a light that flashes at any one of the center frequencies of 32 Hz, 34 Hz, 36 Hz, 38 Hz, and 40 Hz under the control of the above control unit.

8. A step of providing a visual stimulus to a subject by irradiating flashing lights with different center frequencies in the gamma band; A step of measuring gamma band brain waves induced in the brain of a subject while a visual stimulus is provided to the subject; and A method for providing gamma brainwave entrainment for a patient with mild cognitive impairment, characterized by comprising the steps of selecting a center frequency at which gamma band brainwave entrainment is most strongly exhibited as an optimal frequency and providing a visual stimulus to a subject at the selected optimal frequency.

9. In paragraph 8, The step of providing a visual stimulus to the subject at the above-selected optimal frequency is: A method for providing gamma brainwave entrainment for a patient with mild cognitive impairment, characterized in that the method comprises the step of selecting a center frequency at which gamma band brainwave entrainment is most strongly shown among a plurality of center frequencies based on the measured brainwaves as an optimal frequency, and providing a visual stimulus to the subject by irradiating a flashing light at the selected optimal frequency.

10. In paragraph 8, A method for providing gamma brainwave entrainment for a patient with mild cognitive impairment, characterized in that it further includes a step of tracking an optimal frequency that changes over time and providing a visual stimulus to a subject using the tracked optimal frequency.

11. In paragraph 10, The step of providing a visual stimulus to the subject using the above-mentioned tracked optimal frequency is as follows: A step of providing visual stimulation to a subject at an optimal frequency at intervals for a preset period of time, and then providing visual stimulation to the subject by flashing light at different center frequencies again; A step of re-measuring the gamma band brain waves induced in the brain of the subject while the visual stimulus is provided to the subject; and A method for providing gamma brainwave entrainment for a patient with mild cognitive impairment, characterized by comprising the step of re-selecting a center frequency at which gamma band brainwave entrainment is most strongly shown among a plurality of center frequencies based on the re-measured brainwaves as an optimal frequency, and providing a visual stimulus to the subject by irradiating a flashing light at the re-selected optimal frequency.

12. In any one of the clauses 8 to 11, The above optimal frequency is, A method for providing gamma brainwave entrainment for patients with mild cognitive impairment, characterized in that each brainwave signal acquired by center frequency through multiple electrode channels measuring brainwaves in the occipital lobe region among brainwave channels is analyzed, and among optimal frequency candidates determined for each electrode channel based on ERSP (Event Related Spectral Perturbation), the frequency having the largest value while the average of SNR (Signal to Noise Ratio) exceeds a preset value is determined.

13. In paragraph 8, The step of providing a visual stimulus to the subject by irradiating flashing lights with different center frequencies in the above gamma band is as follows: A method for providing gamma brainwave entrainment for a patient with mild cognitive impairment, characterized in that it is a step of providing a visual stimulus to a subject by irradiating a light that flashes at a center frequency set among center frequencies of 32 Hz, 34 Hz, 36 Hz, 38 Hz, and 40 Hz.

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