WO2018131795A2

WO2018131795A2 - Method for memory improvement through brain stimulation

Info

Publication number: WO2018131795A2
Application number: PCT/KR2017/014288
Authority: WO
Inventors: 정천기; 김준식; 전소연
Original assignee: 서울대학교산학협력단
Priority date: 2017-01-16
Filing date: 2017-12-07
Publication date: 2018-07-19
Also published as: JP6716682B2; JP2019508073A

Description

How to improve memory through brain stimulation

The method of improving memory through brain stimulation of the present invention comprises the steps of: (a) the electronic device applying electrical stimulation to the user's brain, measuring the degree of brain response activation in the user's brain cortex area, (b) from the user's brain cortex area Selecting at least one cortical target region, (c) receiving and measuring a general brain response signal of a user by a stimulus in the cerebral cortical target region, and (d) the electronic device at the cortical target region The method may include applying brain activation induced electrical stimulation, measuring a brain response signal after stimulation according to the induced electrical stimulation, and (e) determining whether the brain activity changes by measuring a change in the brain response signal.

The tactile receptors of the peripheral nervous system detect physical changes in the skin. In the somatosensory cortex of the brain, a process that triggers tactile sensation begins based on information coming from the tactile receptors. Information originating in the tactile receptors is known to reach the primary somatosensory cortex (S1) and secondary somatosensory cortex (S2) via the thalamus.

In the primary somatosensory cortex, the mechanical response to the incoming information tends to occur. It is hard to see that primary somatosensory directly decodes all the specific tactile sensations that humans perceive, and so far, the specific tactile sensations that humans perceive are made in coalition ages, including secondary somatosensory cortex and laryngeal parietal cortex. Many are announced. In particular, much is not known about which areas of the brain produce different tactile sensations.

Recently, studies have been attempted to induce touch by stimulating the human brain by invasive and non-invasive methods. However, much research is still required to generate specific touch by directly stimulating the human brain in the absence of any stimulation through the peripheral nervous system. The method of generating various touches by applying brain stimulation to part of primary somatosensory or secondary somatosensory has been studied.

In addition, the hippocampus in the human brain is known as an area for working with memory. It is also known that all information related to memory is processed in the hippocampus and the medial temporal lobe region, which is the nearby area. Recently, brain cortical areas linked to the hippocampus are known to be involved in memory networks, and studies have been attempted to improve memory function by stimulating the human brain by invasive and non-invasive methods.

However, there have been no cases where the stimulation of the hippocampal region in humans has revealed the cortical regions represented by memory-related features and the improvement of memory function through the direct stimulation of these cortical regions.

An object of the present invention is to provide a method for improving memory through brain stimulation, which provides a method for quantitatively analyzing brain response signals or brain waves so as to evaluate human memory function.

In addition, an object of the present invention is to provide a memory stimulation method through the brain stimulation that can be evaluated quantitatively by objectively stimulating utilization protocol and memory performance ability to improve the individual's memory function.

The technical problem to be achieved by the present invention is not limited to the technical problem mentioned above, and various technical problems can be included within the scope apparent to those skilled in the art from the following description.

Memory improvement method through the brain stimulation according to an embodiment of the present invention for solving the above problems, (a) the electronic device to the electrical stimulation to the user brain, the degree of brain response activation in the brain region of the user brain Measuring, (b) selecting at least one brain cortex target region from the user cortical region, (c) receiving and measuring a general brain response signal of a user by a stimulus in the brain cortical target region, (d) the electronic device applying brain activation induced electrical stimulation to the cerebral cortical target region, measuring brain response signal after stimulation according to the induced electrical stimulation, (e) measuring brain activity by measuring a change in brain response signal The method may include determining whether there is a change.

In addition, the memory stimulation method according to an embodiment of the present invention, the electronic device is transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCs), ultrasound It may include at least one of the brain stimulator.

In addition, the method of improving memory through brain stimulation according to an embodiment of the present invention, the step (a) is characterized in that the electronic device to apply electrical stimulation to the hippocampus of the user brain.

In addition, the memory stimulation method according to an embodiment of the present invention, the step (a) of the increase in theta frequency amplitude (theta frequency amplitude) or gamma frequency amplitude (gamma frequency amplitude) It is characterized by measuring the degree of brain response activation through the increase.

At this time, the memory stimulation method through the brain stimulation according to an embodiment of the present invention, the cortical target in the (b) step has the highest correlation with the increase in the amount of theta power or the increase in the gamma power amount It is characterized by selecting the area.

In addition, the method of improving memory through brain stimulation according to an embodiment of the present invention, the step (b) is characterized in that the brain cortical target region of the increase in the brain response activation region is selected as the cortical target region.

In addition, the method of improving memory through brain stimulation according to an embodiment of the present invention, the step (b) wherein the user's cerebral cortex region of the frontal lobe, parietal lobe, medial lobe, hippocampus, lower temporal lobe, central temporal lobe, upper temporal lobe It is characterized by including any one.

In addition, the memory stimulation method according to an embodiment of the present invention, the step (d) is characterized in that the electrical activation induced electrical stimulation to the brain cortical target region physically through invasive or non-invasive method. .

In addition, the method of improving memory through brain stimulation according to an embodiment of the present invention, further comprising the step of (f) deriving a morphological or temporal feature of the brain response signal (evaluate) and evaluating the user's memory capacity It features.

In this case, the method of improving memory through brain stimulation according to an embodiment of the present invention is characterized in that the feature point includes at least one of information of a specific frequency, an amplitude value in a frequency domain, a reaction time, a low frequency, and a high frequency degree. It is done.

In addition, the method of improving memory through brain stimulation according to an embodiment of the present invention, the step (f) is (f1) detecting the brain response signal for each sample signal for measurement, (f2) samples for each target region of the brain Calculating a feature point for each signal, (f3) selecting a sample signal and a target region, and (f4) calculating a storage accuracy of the selected sample signal.

In addition, the memory stimulation method according to an embodiment of the present invention, the step of (f) step (f5) selecting a brain stimulation parameter for inducing a sample signal selected in the target region, (f6) selected And stimulating a signal to a target region with brain stimulation parameters.

In addition, the memory stimulation method according to an embodiment of the present invention, the step (f) is characterized in that the noise signal is removed from the brain response signal and the epoching process (epoching).

Memory stimulation method through the brain stimulation of the present invention, it is possible to improve the ability of memory in the cognitive function of the high-level through the stimulation of the brain cortical region.

In addition, the memory improvement method through the brain stimulation of the present invention, stimulation to improve the memory function in consideration of different characteristics for each individual, and based on the data to measure the brain waves quantitatively based on the memory performance evaluation The degree of identification can be quantified and evaluated.

In addition, the memory stimulation method through the brain stimulation of the present invention can be evaluated by quantifying in order to grasp the degree of the individual's memory function through the response changes in the brain.

In addition, the method of improving memory through brain stimulation of the present invention proposes a cerebral cortex stimulation protocol for non-invasive application in the future based on invasive brain stimulation EEG response, and personalized most effective memory in consideration of individual characteristics You can expect improvements.

In addition, the memory stimulation method through the brain stimulation of the present invention, by analyzing the user's response to extract the characteristics that differ only when the performance of the individual is good, perform the individual's memory to determine the improvement of the individual's cognitive tasks The degree can be quantified.

In addition, the memory stimulation method of the present invention, by using the brain wave of the subject can measure the degree of activation of the individual brain response, by stimulating the target region of the brain can induce improvement of brain function. .

In addition, since the memory stimulation method of the present invention can quantify and predict the accuracy of an individual's memory function based on the brain waves measured at the stage of memory input, it is a clue for determining the accuracy of memory quickly and efficiently. It can be utilized.

1 relates to a method of improving memory through brain stimulation according to an embodiment of the present invention.

Figure 2 relates to a user brain cortical region of the memory stimulation method according to an embodiment of the present invention.

3 relates to a method of selecting a cortical target region of a memory enhancing method through brain stimulation according to an embodiment of the present invention.

Figure 4 relates to the brain activation stimulation of the memory enhancement method through the brain stimulation according to an embodiment of the present invention.

5 relates to a method of evaluating user memory ability in a method of improving memory through brain stimulation according to an embodiment of the present invention.

Figure 6 relates to the difference in theta power as a result of the memory stimulation method through the brain stimulation according to an embodiment of the present invention.

Hereinafter, a method of improving memory through brain stimulation according to the present invention will be described in detail with reference to the accompanying drawings. The described embodiments are provided so that those skilled in the art can easily understand the technical idea of the present invention, and thus the present invention is not limited thereto. In addition, matters represented in the accompanying drawings may be different from the form actually embodied in the schematic drawings in order to easily explain the embodiments of the present invention.

In addition, each component expressed below is only an example for implementing this invention. Thus, other implementations may be used in other implementations of the invention without departing from the spirit and scope of the invention.

In addition, the expression "comprising" certain components merely refers to the presence of the components as an 'open' expression, and should not be understood as excluding additional components.

Also, an expression such as 'first' and 'second' is used only for distinguishing a plurality of configurations, and does not limit the order or other features between the configurations.

In the description of embodiments, each layer, region, pattern, or structure may be “on” or “under” the substrate, each layer, region, pad, or pattern. Substrate formed in ”includes all formed directly or through another layer. Criteria for the top / bottom or bottom / bottom of each layer are described with reference to the drawings.

When a part is said to be "connected" with another part, this includes not only "directly connected" but also "indirectly connected" with another member in between. In addition, when a part is said to "include" a certain component, this means that it may further include other components, without excluding the other components unless otherwise stated.

Human memory goes through three processes: input, consolidation, and retrieval. Among them, the present invention passes through the hippocampus in the medial lobe at the step of inputting the irritants introduced through the human eye. Memory stimulation method through the brain stimulation of the present invention, by utilizing the hippocampus can be improved when the memory is input into the brain.

Referring to FIG. 1, the method of improving memory through brain stimulation of the present invention includes measuring brain activation levels, selecting a cortical target region, receiving and measuring general brain response signals, and brain after stimulation. The method may include measuring a response signal and determining whether brain activity changes.

First, the electronic device may apply electrical stimulation to the user's brain to measure the degree of brain response activation in the user's brain cortex. At this time, the electronic device of the memory stimulation method through the brain stimulation of the present invention, Transcranial Magnetic Stimulation (TMS), Transcranial Direct Current Stimulation (tDCs), at least any one of the ultrasonic brain stimulator It may include one. In addition, all commonly used electronic devices may be used to perform brain stimulation.

In this case, the memory stimulation method through the brain stimulation of the present invention, the electronic device is characterized in that the electrical stimulation to the hippocampus of the user brain. As described above, the hippocampus (hippocampus) among the human brain can control memory, spatial concepts, and emotional behavior. In the method of improving memory through brain stimulation of the present invention, the degree of activation changed in the brain can be measured by directly or indirectly applying electrical stimulation to the hippocampus among user brains.

In addition, it is possible to determine the parameters of the electrical stimulation by comparing the degree of activation of the brain response generated by stimulating the hippocampus, which is a core center of the memory input process. Since the degree of activation of the brain response caused by stimulation of the hippocampus may vary depending on the parameter variable in some people, it is possible to select a variable that can be most clearly shown.

In addition, the memory stimulation method through the brain stimulation of the present invention, it is possible to measure the degree of brain response activation in the brain cortex of the user. In order to determine the variable factor that induces the degree of activation of the brain, the degree of activation may be determined by the amount of change in the brain response that occurs through brain stimulation during the resting period of the human.

More specifically, it is possible to induce brain activity at a total energy amount of 57 μC / cm 2 or less applied to the stimulus in the gamma (50 Hz) frequency region, and the degree of brain improvement may be expected through activation of the brain response. In addition, the degree of brain response activation may be measured by increasing the theta frequency amplitude or the gamma frequency amplitude in the brain cortex. Such increase in theta power amount or gamma power amount is a clue for determining the activation of the brain response.

Referring to FIG. 3, in the method of improving memory through brain stimulation of the present invention, at least one brain cortex target region may be selected from the user brain cortex regions. More specifically, the region where the change in the brain response signal is most clearly determined among the target candidate group regions may be determined, and such region may be selected as the brain cortex target region.

Here, the candidate group region of the brain cortical target region is at least one of the brain regions of the secondary somatosensory cortex, laryngeal parietal cortex, premotor area and auxiliary motor area, or secondary somatosensory cortex, laryngeal parietal cortex, premotor area and auxiliary A boundary region between at least two regions of the exercise region may be included, and the target region may be determined by a method to be described later among the target candidate group regions.

In addition, a region in which the brain response activation is most increased among the user's brain cortex areas may be selected as the brain cortex target area.

In addition, when the brain cortex target region is found, the stimulus target region may be slightly different for each person. In order to solve this difference, the present invention can select a region having the highest correlation with the increase amount of theta power amount or the increase amount of the gamma power amount as the brain cortex target area. In addition, the region having the highest correlation may be selected by contrasting the theta power increase in the brain cortical candidate group region which is induced by stimulating the hippocampus directly or indirectly. In the case of indirect stimulation, analysis of the brain's connectivity around the hippocampus can be used to find a custom cortical target region.

Referring to FIG. 3, an embodiment of correlation analysis may be confirmed. In the present invention, one of correlation or coherence values may be used to obtain a correlation value. In addition, since the position of the brain cortical region where the brain response occurs may vary depending on a person, the target candidate region of the stimulus for measurement may include at least one of the frontal lobe, parietal lobe, medial temporal lobe, hippocampus, lower temporal lobe, central temporal lobe, and upper temporal lobe. It may include.

Referring to FIG. 3, it is possible to determine a location having the highest correlation with the hippocampus among the brain cortical regions. The x-axis is the amplitude signal from the electrode belonging to the hippocampus, and the y-axis is the amplitude signal from the target brain cortex. The closer the R ² value is to 1 in the graph, the higher the correlation. The P value represents the significance level of the presented value.

Figure 4 relates to the brain activation stimulation of the memory enhancement method through the brain stimulation according to an embodiment of the present invention, Figure 5 evaluates the user memory capacity of the memory enhancement method through the brain stimulation according to an embodiment of the present invention It is about how to.

4 and 5, the method of improving memory through brain stimulation of the present invention may include receiving and measuring a general brain response signal of a user by a stimulus in the brain cortex target region. At this time, the user cerebral cortex region may include at least one of the frontal lobe, parietal lobe, medial temporal lobe, hippocampus, lower temporal lobe, central temporal lobe, upper temporal lobe.

In order to perform a memory task for a person, first, a stimulus related to memory may be proposed to remember the stimulus. For example, the stimulus may be a visual presentation of a picture, a word, or the like.

Next, a visual presentation can be shown to process the brain response signal and the brain response to it can be measured as a signal. The brain response signal measurement may receive a brain response signal in at least one region of the human brain target candidate region.

More specifically, the brain response signal measuring step of the present invention may be based on invasive brain activity, ie, signals from the subdural cortex. Therefore, it may include electrocorticography (ECoG) of invasive brain activity measurement.

Next, the method of improving memory through brain stimulation of the present invention may include: applying, by the electronic device, brain activation target electrical stimulation to the brain cortex target region, and measuring a brain response signal after stimulation according to the induced electrical stimulation. Can be.

More specifically, when inducing stimulation to the human, induction stimulation can be applied to the temporal cortex of the human brain. In this case, the induction stimulus may be an electrical brain stimulation. The apparatus for stimulating the brain cortex may include at least one of the above-described transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCs), and ultrasonic brain stimulator. In addition, all commonly used electronic devices may be used to perform brain stimulation.

At this time, the brain activation induced electrical stimulation may be physically applied to the cortical target region through invasive or non-invasive methods. After physical stimulation with the parameters determined in the target area, it is possible to determine whether there is a correct answer to the result of the action, and the feature point can be determined according to the person in the target area.

Referring to Figure 4, the brain response difference before and after brain activation stimulation can be confirmed. In each graph, the x axis represents frequency and the y axis represents the amplitude of the signal. The unit of time may use seconds. The amplitude units of the measured brain response graph and the derived brain response graph may be μV.

In addition, it may be determined depending on whether a positive amplitude value before and after stimulation in a low gamma frequency region (30-60 Hz) and theta frequency region (3-8 Hz) is measured as a measure of brain activation. . In addition, brain stimulation caused by pulses of high frequency (eg, 140 Hz) or more may suppress brain activity.

Meanwhile, the method of improving memory through brain stimulation of the present invention may further include determining whether the brain activity changes by measuring a change in the brain response signal.

More specifically, the brain response signal indicating the response of the human brain in response to an applied stimulus can be measured. In addition, when the response of the human brain changes as the applied stimulus changes, the change in the brain response signal according to the change of the stimulus can be measured. In particular, the response of the subject between 0 and 1 second in the target candidate group is also measured. As a result, the change in the brain response signal of the theta power amount or the gamma power amount is measured, and it is possible to determine whether the change in brain activity due to brain stimulation is shown.

Meanwhile, the method of improving memory through brain stimulation of the present invention may further include deriving a morphological or temporal feature of the brain response signal and evaluating user memory ability. In this case, the feature point of the present invention may include information of at least one of a specific frequency, an amplitude value in a frequency domain, a reaction time, a low frequency, and a high frequency level.

In addition, the memory enhancement method of the brain stimulation of the present invention, in order to utilize the brain response as a cognitive function evaluation for the feature point derivation analysis of EEG information of any one of time-frequency analysis, phase locking value, phase-phase coupling value Method can be used.

As a method of quantifying and evaluating the degree of the individual's memory function through the response change in the brain, the present invention can use the characteristic analysis of EEG using a computer. The characteristic point is that the morphological and temporal features of the brain waves measured in a plurality of trials are identified in an iterative form by dividing and observing the accuracy of the cognitive task.

In particular, the method used to implement the derived feature points through brain stimulation generates an electrical stimulus having a specific frequency and parameter in the cerebral cortex so that the feature points can be derived for the electrical stimulus, thereby improving memory function. Can be.

Referring to FIG. 5, the method of improving memory through brain stimulation according to the present invention includes: (f1) detecting brain response signals for each sample signal for measurement, and (f2) calculating feature points for each sample signal for each target region of the brain. (f3) selecting a sample signal and a target region, (f4) calculating a storage accuracy of the selected sample signal, (f5) selecting a brain stimulation parameter for inducing a selected sample signal in the target region, ( f6) stimulating the selected signal to the target region with brain stimulation parameters.

More specifically, an EEG input unit for receiving EEG data to be used for evaluating memory functional ability, an EEG preprocessing unit for removing noise signals from the EEG data and epoching, and generating artificial data using the EFO processed EEG data It may include a statistical processing unit, an evaluation processing unit for determining the significance degree and accuracy of a specific time and a specific frequency between the forked processing EEG data, and a memory unit for storing artificial data and results.

More specifically, the accuracy evaluation of memory may be based on theta waves (3-8 Hz) or gamma waves (30-50 Hz) that increase when the subject performs the given task correctly in the encoding process. The characteristics of the frequency band as a reference can be calculated by increasing power or phase resetting values in the interval immediately before (-2 to 0 sec) or immediately after (0 to 2 sec) the visual stimulus for the memory task. Prediction is also possible through the appearance of the previous section.

When feature points are calculated for each sample signal for each brain region, significant values are selected according to the amplitude and the value of the signal. In the accuracy calculation step, the detected EEG signal may be used to evaluate the threshold value based on the feature points of the theta and gamma frequency domains of the user for each sample signal compared to the incorrect and correct answers. Below the threshold, a higher accuracy sample signal can be selected again.

At this time, the region of the EEG to be a reference may be divided into theta wave (3-8Hz), gamma wave (30-50Hz). Therefore, while the user performs the memory task, the brain waves may be analyzed for each frequency, and may be determined as a quantitative value.

Embodiments of the invention described above are disclosed for purposes of illustration, and the invention is not limited thereto. In addition, one of ordinary skill in the art of the present invention will be able to add various modifications and changes within the spirit and scope of the present invention, these modifications and changes will be considered to be within the scope of the present invention.

[Description of the code]

S110: measuring the degree of brain response activation

S120: step of selecting a brain cortex target area

S130: step of receiving and measuring a general brain response signal

S140: measuring brain response signal after stimulation

S150: step of determining whether the brain activity changes

Claims

(a) the electronic device applying electrical stimulation to the user's brain to measure the degree of brain response activation in the user's brain cortex area;

(b) selecting at least one cortical target region from the user cortical regions;

(c) receiving and measuring a general brain response signal of a user by a stimulus in the brain cortex target region;

(d) the electronic device applying brain activation induced electrical stimulation to the brain cortex target region and measuring a brain response signal after stimulation according to the induced electrical stimulation;

(e) determining a change in brain activity by measuring a change in brain response signal;

Memory enhancement method through brain stimulation comprising a.
The method of claim 1,

The electronic device,

Transcranial Magnetic Stimulation (TMS), Transcranial Direct Current Stimulation (tDCs), Ultrasound brain stimulator, characterized in that it comprises at least one of the brain stimulator.
The method of claim 1,

In step (a),

And the electronic device applies electrical stimulation to the hippocampus of the user's brain.
The method of claim 1,

In step (b),

The cerebral cortex area of the user,

Method for improving memory through brain stimulation, comprising at least one of the frontal lobe, parietal lobe, medial temporal lobe, hippocampus, lower temporal lobe, central temporal lobe, upper temporal lobe.
The method of claim 1,

In step (a),

A method for improving memory through brain stimulation, characterized by measuring the extent of brain response activation through an increase in theta frequency amplitude or an increase in the gamma frequency amplitude in the cerebral cortex.
The method of claim 5,

In step (b),

And a region having the highest correlation with the increase amount of theta power amount or the increase amount of the gamma power amount is selected as a brain cortex target area.
The method of claim 1,

In step (b),

A method for improving memory through brain stimulation, comprising selecting a region of the user's cerebral cortex that has the highest brain response activation as a brain cortex target region.
The method of claim 1,

In step (d),

A method of improving memory through brain stimulation, characterized by physically applying brain activation-induced electrical stimulation to a cortical target region through invasive or non-invasive methods.
The method of claim 1,

(f) deriving a morphological or temporal feature of the brain response signal and evaluating user memory ability;

Memory stimulation method through the brain stimulus, characterized in that it further comprises.
The method of claim 9,

The feature point,

A method for improving memory through brain stimulation, comprising at least one of information of a specific frequency, amplitude value in a frequency domain, response time, low frequency, and high frequency.
The method of claim 9,

Step (f),

(f1) detecting brain response signals for each measurement sample signal;

(f2) calculating a feature point for each sample signal for each target region of the brain;

(f3) selecting a sample signal and a target region;

(f4) calculating the storage accuracy of the selected sample signal;

Memory stimulation method through a brain stimulus comprising a.
The method of claim 11,

Step (f),

(f5) selecting brain stimulation parameters for inducing a selected sample signal in the target region;

(f6) stimulating the selected signal to the target region with brain stimulation parameters;

Memory stimulation method through the brain stimulus, characterized in that it further comprises.
The method of claim 9,

Step (f),

A method of improving memory through brain stimulation, characterized in that the noise signal is removed from the brain response signal and subjected to epoching.