KR20220039433A - APPARATUS AND METHOD FOR NeuromodulatinG for improving tinnitus and related cognitive impairment - Google Patents

Abstract

The present specification discloses an apparatus and method for improving tinnitus and cognitive function. A neuromodulating apparatus and method according to the present specification measure the degree of frequency synchronization for each individual, generate a similar electrical signal, and apply it through the skin of a head to activate frequency synchronization, thereby improving tinnitus and cognitive function.

Description

Neuromodulation apparatus and method for improving tinnitus and related cognitive impairment

The present invention relates to brain waves, and more particularly, to a technology for activating brain waves to improve tinnitus and cognitive function.

Brain wave refers to a microscopic signal at the uV level measured from the scalp that measures the electrical activity of groups of nerve cells constituting the cerebral cortex. EEG (Electro EncephaloGram) means measuring and recording the electrical changes that are generated accompanying the activity of brain nerve cells. EEG signals change spatially and temporally according to brain activity, state at the time of measurement, and brain function, and EEG measurement is an essential process for diagnosing brain functions and disorders.

The measured EEG has a frequency of 1~50Hz and an amplitude of about 10~200uV. Depending on the difference in frequency and voltage, delta waves (0.2~4Hz, 20~200uV) in normal sleep and theta waves in emotionally stable cases (4 ~7Hz, 20~100uV), alpha wave (8~12Hz, 20~60uV) in a relaxed state, beta wave (12~30Hz, 2~20uV) when excited, gamma wave ( 30~50Hz, 2~20uV), etc.

On the other hand, tinnitus is a symptom of continuous sound from the ear or head without an actual external sound stimulus. Usually, it is secondary to damage to the peripheral auditory organ, but there are cases in which tinnitus is not present even in people with damage to the auditory organ. The exact mechanism by which this occurs is not known so far. Therefore, according to the theory established so far, since auditory cognition is a unique function of the cerebral cortex, it is considered that the problem of the central auditory cognition process in the cerebral cortex connected to the peripheral auditory organs occurs complexly and causes tinnitus. In many other studies, it has been demonstrated that the cerebral neuronal structures connected to the peripheral auditory organs in a person complaining of tinnitus are different from those of normal adults without tinnitus, and it has been reported that some of the neuronal structures are overactivated. In particular, significant cognitive decline is observed in people with tinnitus, and the cognitive decline accompanying tinnitus can become a serious social problem.

To date, there are no drugs that have been proven effective from the standpoint of evidence-based medicine to relieve the symptoms of tinnitus, and additionally attempted trans-magnetic stimulation or trans-electrical stimulation Neuromodulation is used to improve tinnitus symptoms through artificial brain activity control through cerebral stimulation based on the theoretical background mentioned above.

However, in reality, the degree of recognizing tinnitus is different for each person, there are individual differences in sound sensitivity, and even though there are differences in brain function activity or connection structure, the uniform stimulation method has inherent limitations, and its effectiveness has been proven from the standpoint of evidence-based medicine. Therefore, it cannot be practically applied in clinical practice.

On the other hand, in the cerebrum, various information is connected to each other through electrical signals, and each part of the brain performs a cognitive function through the connection of electrical signals having various frequency components, and the recognition of sound is performed in the same way. In this case, an electric signal of a slow frequency component is responsible for information movement over a long distance, and an electric signal of a fast component is responsible for information movement in an adjacent area. However, since each region of the cerebrum emits electrical signals with various properties rather than independent components, our brain puts a signal with a frequency property of a fast component on a signal with a frequency component of a slow component to prevent the movement of information. This is called cross frequency coupling (cross frequency coupling).

Unexamined Patent Publication No. 10-2018-0110156 (2018.10.08)

An object of the present specification is to provide an apparatus and method for improving tinnitus and cognitive function.

The present specification is not limited to the above-mentioned problems, and other problems not mentioned will be clearly understood by those skilled in the art from the following description.

A neuromodulation apparatus according to the present specification for solving the above-described problems includes: a fundamental frequency identification unit for identifying a fundamental frequency of a subject from signals measured from a plurality of EEG electrodes installed on the scalp of the subject; a CFC pattern generator for generating a cross-frequency coupling (CFC) pattern by using the identified fundamental frequency; and an electrical stimulation unit that outputs the generated CFC pattern as an electrical signal to the subject for a preset time through the plurality of EGG electrodes.

According to an embodiment of the present specification, the fundamental frequency identification unit may use EEG data measured for a preset time in a state in which the subject is in a closed eye state.

According to an embodiment of the present specification, the fundamental frequency identification unit may analyze the measured signal in the frequency domain, but may identify a frequency having the maximum power within the alpha wave range in the frequency power spectrum as the fundamental frequency.

According to an embodiment of the present specification, the CFC pattern generator may generate a frequency (hereinafter, 'high frequency') having an arbitrary magnification of the identified fundamental frequency and use it for pattern generation.

In this case, the CFC pattern generator may generate a cross-frequency coupling (CFC) pattern by synthesizing the fundamental frequency and the high frequency.

The neuromodulation apparatus according to the present specification may further include a stimulation analyzer that compares and analyzes EEG data before and after stimulation with the cross-frequency coupling (CFC) pattern stimulation.

Neuromodulation method according to the present specification for solving the above-described problems, the processor comprising the steps of (a) measuring a signal from a plurality of EEG electrodes installed on the scalp of the subject; (b) identifying a fundamental frequency of the subject from the measured signal; (c) generating a cross-frequency coupling (CFC) pattern using the identified fundamental frequency; and (d) outputting the generated CFC pattern as an electrical signal to the subject for a preset time through the plurality of EGG electrodes.

According to one embodiment of the present specification, the step (a) may be a step of acquiring EEG data measured for a preset time in the lung eye state of the subject.

According to an embodiment of the present specification, the step (b) may be a step of analyzing the measured signal in the frequency domain, and identifying a frequency having the maximum power within the alpha wave range in the frequency power spectrum as the fundamental frequency.

According to an embodiment of the present specification, step (c) may be a step of generating a frequency having an arbitrary magnification of the identified fundamental frequency and using it to generate a pattern.

In this case, step (c) may be a step of generating a cross-frequency coupling (CFC) pattern by synthesizing the fundamental frequency and the high frequency.

The neuromodulation method according to the present specification may further include comparing and analyzing EEG data before and after stimulation with the cross-frequency coupling (CFC) pattern.

The neuromodulation method according to the present specification may be implemented in the form of a computer program recorded in a computer-readable recording medium written to perform each step of the neuromodulation method in a computer.

Other specific details of the invention are included in the detailed description and drawings.

According to one aspect of the present specification, it is possible to determine the state of the tinnitus patient by identifying the neurophysiological process control response state that reflects the occurrence of tinnitus occurring in the central nervous system of the patient and the cognitive decline associated therewith.

According to another aspect of the present specification, it is possible to provide an optimal neuromodulation method for improving symptoms according to the patient's tinnitus and related cognitive decline characteristics.

According to another aspect of the present specification, it is possible to provide a tinnitus-cognitive healthcare solution model that automates tinnitus patient status determination and symptom improvement.

Effects of the invention are not limited to the effects mentioned above, and other effects not mentioned will be clearly understood by those skilled in the art from the following description.

1 is a block diagram schematically showing the configuration of a neuromodulation apparatus according to the present specification.
2 is a flowchart schematically illustrating a flow of a neural modulation method according to the present specification.
3 is a reference diagram of an EEG measurement location.
4 to 6 are exemplary views of generating a CFC pattern.

Advantages and features of the invention disclosed herein, and a method of achieving them will become apparent with reference to the embodiments described below in detail in conjunction with the accompanying drawings. However, the present specification is not limited to the embodiments disclosed below, but may be implemented in various different forms, and only the present embodiments allow the disclosure of the present specification to be complete, and those of ordinary skill in the art to which this specification belongs. It is provided to fully inform those skilled in the art (hereinafter referred to as 'those skilled in the art') the scope of the present specification, and the scope of the present specification is only defined by the scope of the claims.

The terminology used herein is for the purpose of describing the embodiments and is not intended to limit the scope of the present specification. In this specification, the singular also includes the plural unless specifically stated otherwise in the phrase. As used herein, “comprises” and/or “comprising” does not exclude the presence or addition of one or more other components in addition to the stated components.

Like reference numerals refer to like elements throughout, and "and/or" includes each and every combination of one or more of the recited elements. Although "first", "second", etc. are used to describe various elements, these elements are not limited by these terms, of course. These terms are only used to distinguish one component from another. Accordingly, it goes without saying that the first component mentioned below may be the second component within the spirit of the present invention.

Unless otherwise defined, all terms (including technical and scientific terms) used herein will have the meaning commonly understood by those of ordinary skill in the art to which this specification belongs. In addition, terms defined in a commonly used dictionary are not to be interpreted ideally or excessively unless specifically defined explicitly.

When a person thinks or performs a cognition, the brain regions involved emit electrical signals with various properties. Signals commonly referred to as brain waves travel through various regions of the brain, and the frequencies of the slow and fast components are connected in synchronization with each other (cross frequency coupling). Applicants have discovered that this frequency synchronization is altered when tinnitus is present. Since the synchronized frequency may be different for each individual, the degree of frequency synchronization should be measured for each individual in order to alleviate tinnitus. And it was discovered that, when an electrical signal similar to the measured signal was made and applied to a tinnitus patient, activation of frequency synchronization could be expected. Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings.

1 is a block diagram schematically showing the configuration of a neuromodulation apparatus according to the present specification.

Referring to FIG. 1 , the neuromodulation apparatus 100 according to the present specification may include a fundamental frequency identification unit 110 , a CFC pattern generation unit 120 , and an electrical stimulation unit 130 .

The fundamental frequency identification unit 110 may identify the fundamental frequency of the examinee from signals measured from the plurality of EEG electrodes 101 installed on the scalp of the examinee.

The CFC pattern generator 120 may generate a Cross Frequency Coupling (CFC) pattern by using the identified fundamental frequency.

The electrical stimulation unit 130 may output the generated CFC pattern as an electrical signal to the subject for a preset time through the plurality of EGG electrodes 101 .

2 is a flowchart schematically illustrating a flow of a neuromodulation method according to the present specification.

Referring to FIG. 2 , first, the brain wave of the subject may be measured in step S110. For EEG measurement of a subject, signals may be measured from a plurality of EEG (Electroencephalography) electrodes installed on the subject's scalp.

According to an embodiment of the present specification, based on the international 10-20 system, open-eye operation in a resting state through 32, 64, or 128 EEG electrodes installed on the scalp of a subject (patient) EEG can be measured for 2 minutes while keeping an eye on the '+' mark displayed on the screen. Then, it is possible to measure the EEG for 2 minutes with a close-eye operation. Again, the EEG can be measured with an open-eye operation for 3 minutes and a close-eye operation for 3 minutes. Although EEG data corresponding to 5 minutes of open/close-eye is required, if EEG is measured continuously for 5 minutes in close-eye operation, some subjects (patients) will experience drowsiness. Therefore, in order to prevent this, it is preferable to measure the open eye and close eye movements separately. Thereafter, each of the measured signal data may be combined to be reconstructed into EEG data of 5 minutes for open eyes and 5 minutes for lung eyes.

In the next step S120, the fundamental frequency of the subject may be identified from the measured signal. This step is to find different brain waves for each individual, that is, a synchronized frequency in real time. Tinnitus symptoms and cognitive decline are related to the weakening of the control function of the central nervous system (Alpha inhibition model). Tinnitus can be caused by an overstatement of the cerebral cortex or failure of control due to damage to the peripheral auditory organs. The main areas responsible for the control function are the frontal, central, or temporal lobes, which are emotional areas that perceive and feel sounds. In addition, these areas correspond to the intersection of functions distributed in the brain and are related to cognitive function, and in particular, the temporal lobes located on the left and right sides contain the auditory cortex and are correlated with the regulation of brain functions linked to tinnitus symptoms. The frontal lobe controls the temporal lobe through the central part. Compared to normal people, people who experience tinnitus show a markedly reduced difference in the intensity of communication between the central nervous system, that is, in the ability to transmit information. It is necessary to identify the so-called 'drive frequency', that is, the fundamental frequency, which is the most basic in mediating the Since the fundamental frequency may be different for each patient, it is necessary to read the exact fundamental frequency for each patient to enable the coding of the next-level accurate current stimulation pattern for nerve modulation.

According to an embodiment of the present specification, EEG data measured in time series at each electrode may be converted into a frequency domain by applying a Fast Fourier Transform (FFT) technique. At this time, it is expressed as a frequency power spectrum value in each frequency domain converted to the frequency domain. After taking only the frequency region corresponding to the alpha band (8-12Hz) from the average value for the electrode, it is possible to identify this as the fundamental frequency by reading a single frequency showing the maximum power spectrum (Max peak). Since this reading process can be performed by a linear search method, it is possible to proceed in real time, so that it is possible to read and determine a reference frequency in real time from EEG data measured from a patient. It is implemented in MATLAB, and if other implementation methodologies (eg, python, C++/C#, etc.) are applied, faster implementation than MATLAB is possible.

In the next step S130, a cross frequency coupling (CFC) pattern may be generated using the identified fundamental frequency.

The cross-frequency coupling pattern is a combination of electrical stimulation to modulate a nerve. The CFC is a model for extracting characteristic elements from two types of frequencies constituting one waveform and analyzing their relationship, and conversely, two waveforms may be synthesized into one overlapping waveform according to the same principle. In CFC, there are two main frequency characteristics to be observed from the waveform, one is the phase and the other is the amplitude. Accordingly, three combinations of phase-phase tuning, phase-amplitude tuning, and amplitude-amplitude tuning are possible according to their combination. All three combinations of the neural modulation method according to the present specification are possible, but in this specification, an example of phase-amplitude tuning will be described.

As previously described, long-distance information transmission between regions related to the symptom in the tinnitus brain with cognitive decline (i.e., transmission between regions distant from the brain, such as between different lobes, such as Fz to Cz, see Fig. 3) pattern and It has a similar shape, and this pattern-based current stimulation tuning compensates for and induces amplification of the insufficient information and transmission ability in patients compared to normal people. The patient's reference frequency corresponds to a low frequency that performs alpha-inhibition control that affects the patient's overall brain function. The low frequency, that is, the high frequency to be transmitted to the tinnitus and cognitive function performing part after being carried on the existing frequency contains control information of tinnitus and cognitive function, and generally belongs to a high gamma band (50 to 250 Hz or more).

4 to 6 are exemplary views of generating a CFC pattern.

Referring to FIG. 4 , an example of a fundamental frequency can be confirmed. For convenience, the existing frequency will be referred to as 'Phase'. The phase of the fundamental frequency may be divided into two, for example, 0 degrees/180 degrees. In the example shown in FIG. 4 , a fundamental frequency having a phase of 180 degrees is assumed.

The frequency of the high gamma wave may also be multiplied in proportion to the frequency of the alpha wave corresponding to the reference frequency. The magnification may be preset in various ways. As an example, it is possible to select a tuned value (customized to the patient) or a fixed magnification value (universal) according to the characteristics of the symptoms experienced by the patient (subject). In the case of a general-purpose magnification value, since the integer values of the alpha wave are limited to 8, 9, 10, 11, and 12, five integer values of the corresponding high gamma wave can also be specified. In this case, it is possible to perform CFC stimulation pattern coding in advance using a predefined value, and then immediately execute without pattern coding at the actual stimulation time. In addition, in general, the frequencies of alpha and high gamma waves use integer values (eg, alpha 8Hz, high gamma 120Hz), but if necessary, it can be determined by searching for frequencies that consider even decimal places for patient precision (eg, : alpha 10.6Hz, high gamma 127.2Hz).

Referring to FIG. 5 , an example of a high-frequency waveform generated by using an arbitrary magnification value on an existing frequency can be confirmed. For convenience, the existing frequency will be referred to as 'Amplitude'. In the example shown in FIG. 5, 'Phase' is shown in blue and 'Amplitude' is shown in red.

Next, when the existing frequency and the high frequency are determined, a cross-frequency coupling (CFC) pattern may be generated by synthesizing the two waveforms into one waveform. Referring to FIG. 6 , an example of a cross-frequency coupling (CFC) pattern generated by synthesizing two waveforms can be confirmed.

Referring back to FIG. 2 , in the next step S140, the generated CFC pattern may be output as an electrical signal to the subject for a preset time through the plurality of EGG electrodes.

The output of the electrical signal is a signal for giving electrical stimulation to a subject (patient). Among the plurality of electrodes previously attached to the scalp of the subject (patient) for EEG measurement, only a small number of electrodes selected to present current stimulation can be replaced (EEG measurement electrode -> tACS stimulation electrode). This reduces the measurement time and maximizes patient convenience by restoring only the electrodes to their original state (tACS stimulation electrode -> EEG measurement electrode) during the second EEG measurement, which will be described later.

The electrical signal may be output within a predetermined current range for a predetermined time. For example, the generated CFC pattern may be generated for about 1 minute, and may be repeated about 20 times in order to stimulate the scalp of a patient for about 20 minutes. The current is set in the range of 1.5 to 2.5 mA by combining reports from several studies, and it is desirable that the determined current be kept fixed while the stimulus is presented. As the strength of the current increases, the stimulation is stronger, so it can be expected that the effect will be higher.

Since the electrode from which the electrical signal is output is based on the tinnitus experienced by the patient, it is preferable to apply it to the frontal region, the left temporal region and the right temporal region. More specifically, it is preferable to apply to F4, T7, and T8. The stimulation area is not limited to this area and can be applied in various areas. For example, F4 may be set as an anodal (excitatory) current stimulating electrode, and T7 (corresponding to left tinnitus) and/or T8 (corresponding to right tinnitus) may be set as current convergence electrodes. Central tinnitus accompanied by cognitive decline is a symptom caused by insufficient transmission of auditory suppression control information on the pathway from the frontal and central parts of the brain to the temporal lobe. By presenting the information transmission pattern as a CFC current stimulus, the corresponding pathway can be activated.

The neuromodulation apparatus according to the present specification may further include a stimulation analyzer 140 .

The stimulus analyzer 140 may compare and analyze EEG data before and after stimulation with the cross-frequency coupling (CFC) pattern. Specifically, after removing the tACS stimulation electrode attached for the CFC pattern stimulation, EEG is measured in the entire scalp based on the international 10-20 system in the same manner as in the previous procedure. In the same manner, measurements may be performed in the order of 3 minutes for open eyes, 2 minutes for open eyes, 2 minutes for open eyes, and 3 minutes for closed eyes. In this case, the fundamental frequency may be re-extracted using the measured signal.

The comparative analysis is intended to quantify the effect of CFC current stimulation and establish scheduling for the next session. Through reading of CFC markers (markers explored in previous studies) related to tinnitus and cognitive function, and pre-stimulation EEG and control analysis, the effect of CFC current stimulation can be quantified and scheduling for the next session can be established.

7 is an illustration of a control assay before and after CFC current stimulation.

Referring to FIG. 7 , as a result of control analysis before and after CFC current stimulation in tinnitus symptomatic patients, the degree of CFC with respect to the phase in the Cz region and the amplitude in T7 is shown. In the pre-stimulation state (before), CFC between delta and gamma waves is not observed. However, CFC is observed as seen after stimulation of the CFC current for 20 minutes by the neuromodulation method according to the present specification (yellow colored part in the figure below). Through these objective signs, the effect of current stimulation can be calculated, and if sufficient CFC is observed after stimulation, this can be repeated.

The fundamental frequency identification unit 110, the CFC pattern generation unit 120, the electrical stimulation unit 130 and the stimulation analysis unit 140 are a processor known in the art to which the present invention belongs to execute calculation and various control logic; It may include an application-specific integrated circuit (ASIC), other chipsets, logic circuits, registers, communication modems, data processing devices, and the like. In addition, when the above-described control logic is implemented in software, the fundamental frequency identification unit 110 , the CFC pattern generation unit 120 , the electrical stimulation unit 130 , and the stimulation analysis unit 140 are implemented as a set of program modules. can be In this case, the program module may be stored in the memory and executed by the processor.

The program is, in order for the computer to read the program and execute the methods implemented as a program, C/C++, C#, JAVA, Python, which the processor (CPU) of the computer can read through the device interface of the computer; It may include code coded in a computer language such as machine language. Such code may include functional code related to a function defining functions necessary for executing the methods, etc., and includes an execution procedure related control code necessary for the processor of the computer to execute the functions according to a predetermined procedure. can do. In addition, the code may further include additional information necessary for the processor of the computer to execute the functions or code related to memory reference for which location (address address) in the internal or external memory of the computer to be referenced. there is. In addition, when the processor of the computer needs to communicate with any other computer or server located remotely in order to execute the above functions, the code uses the communication module of the computer to determine how to communicate with any other computer or server remotely. It may further include a communication-related code for whether to communicate and what information or media to transmit and receive during communication.

The storage medium is not a medium that stores data for a short moment, such as a register, a cache, a memory, etc., but a medium that stores data semi-permanently and can be read by a device. Specifically, examples of the storage medium include, but are not limited to, ROM, RAM, CD-ROM, magnetic tape, floppy disk, and an optical data storage device. That is, the program may be stored in various recording media on various servers accessible by the computer or in various recording media on the computer of the user. In addition, the medium may be distributed in a computer system connected to a network, and a computer-readable code may be stored in a distributed manner.

As mentioned above, although the embodiments of the present specification have been described with reference to the accompanying drawings, those of ordinary skill in the art to which this specification belongs can realize that the present invention may be embodied in other specific forms without changing the technical spirit or essential features thereof. you will be able to understand Therefore, it should be understood that the embodiments described above are illustrative in all respects and not restrictive.

100: neuromodulator
110: basic frequency identification unit
120: CFC pattern generator
130: electrical stimulation unit
140: stimulus analysis unit

Claims (13)

a fundamental frequency identification unit for identifying a fundamental frequency of a subject from signals measured from a plurality of EEG electrodes installed on the subject's scalp;
a CFC pattern generator for generating a cross-frequency coupling (CFC) pattern by using the identified fundamental frequency; and
and an electrical stimulation unit for outputting the generated CFC pattern as an electrical signal to the subject for a preset time through the plurality of EGG electrodes. The method according to claim 1,
The fundamental frequency identification unit, Neuromodulation apparatus, characterized in that the subject uses the EEG data measured for a preset time in a state of the lungs. The method according to claim 1,
The fundamental frequency identification unit analyzes the measured signal in a frequency domain, and identifies a frequency having a maximum power within an alpha wave range in a frequency power spectrum as a fundamental frequency. The method according to claim 1,
The CFC pattern generator generates a frequency (hereinafter, 'high frequency') having an arbitrary magnification of the identified fundamental frequency, and uses it to generate a pattern. 5. The method according to claim 4,
The CFC pattern generator generates a cross-frequency coupling (CFC) pattern by synthesizing the fundamental frequency and the high frequency. The method according to claim 1,
The neuromodulation apparatus further comprising a stimulation analyzer to compare and analyze the EEG data before and after stimulation with the cross-frequency coupling (CFC) pattern stimulation. the processor
(a) measuring a signal from a plurality of EEG electrodes installed on the subject's scalp;
(b) identifying a fundamental frequency of the subject from the measured signal;
(c) generating a cross-frequency coupling (CFC) pattern using the identified fundamental frequency; and
(d) outputting the generated CFC pattern as an electrical signal to the subject for a preset time through the plurality of EGG electrodes; Neuromodulation method comprising a. 8. The method of claim 7,
The step (a) is a neuromodulation method of acquiring EEG data measured for a preset time in the lung eye state of the subject. in claim 7
In the step (b), the measured signal is analyzed in the frequency domain, and a frequency having the maximum power within the alpha wave range in the frequency power spectrum is identified as the fundamental frequency. in claim 7
The step (c) is a neural modulation method in which a frequency having an arbitrary magnification of the identified fundamental frequency is generated and used for pattern generation. in claim 10
The step (c) is a step of generating a cross-frequency coupling (CFC) pattern by synthesizing the fundamental frequency and the high frequency. in claim 7
(e) comparing and analyzing the EEG data before and after stimulation with the cross-frequency coupling (CFC) pattern; A computer program recorded in a computer-readable recording medium written to perform each step of the neuromodulation method according to any one of claims 7 to 12 in a computer.

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