JP7075648B2 - A computer program product that executes a brain function disease identification method and a program including the method. - Google Patents

Description

The present invention relates to a brain function disease discrimination method for discriminating brain function diseases including dementia and neurological diseases (psychiatric disorders), and a computer program product for executing a program including the methods.

In recent years, with the aging society, dementia has become a serious concern. Usually, dementia progresses with age, and it is recognized that it is difficult to clearly grasp the onset time. In addition, while it is difficult to recover from dementia when it actually develops and the symptoms progress, it is possible to prevent the onset by paying attention to the usual lifestyle, etc. It is also known to slow down its progression by taking appropriate measures (including suspicious conditions).

For this reason, recently, systems such as "family doctors for dementia and dementia support doctors" that impose training on general physicians for early detection and early response to dementia are becoming widespread. In addition, in connection with this, the inventor of the present case has an early risk of dementia by acquiring sleep data using a sleep test device at home without the subject going to a special diagnostic institution or the like. We also propose a dementia risk determination system that can be detected (see Patent Document 1).

Japanese Unexamined Patent Publication No. 2016-22310

By the way, there are nearly 80 causative diseases of dementia, but dementia in Japan includes Alzheimer's disease (also referred to as "AD"), Lewy body dementia (also referred to as "DLB"), and vascular dementia. Three types account for 90%. Although vascularity is not misjudged because the cause is rapid, AD and DLB are often combined, although there is a marked difference in typical cases, so sleep data alone is not enough. Or, with the experience and knowledge of a short course as mentioned above, or with only a doctor who does not have sufficient experience, it is difficult to make an accurate distinction, and the patient is overlooked or misdiagnosed (nerve / mental illness and dementia). May be confused, or misjudgment of dementia type).

In addition, in such a wide range of neuropsychiatric disorders, schizophrenia and depression (hereinafter referred to as "depression") are particularly confusing in relation to dementia, and these cannot be accurately distinguished. There is a possibility that the symptoms cannot be improved or worsened due to improper treatment or incorrect prescription.

The present invention has been made on the basis of the above problems and is effective in treating brain dysfunctions, particularly at least Alzheimer's disease and Lewy body dementias, and preferably schizophrenia and depression, with high accuracy. It is an object of the present invention to provide a brain function disease identification method that can be easily differentiated, and a computer program product that executes a program including the method.

In order to achieve the above-mentioned object, the brain function disease discrimination method of the present invention is based on the waveform of the activated EEG when at least visual stimulus, auditory stimulus, and olfactory stimulus are given to the subject, and the apex latency and amplitude. The measurement result obtained by measuring the above is compared with the average value of the apex latency and amplitude of the activated EEG obtained in advance when each stimulus is given to the average elderly person, and the measurement result of each stimulus is averaged. It is characterized by distinguishing whether it corresponds to Alzheimer-type dementia, Levy body-type dementia, schizophrenia, or depression based on whether or not it falls below the value.

According to this method for differentiating brain function diseases, at least three stimuli useful for differentiating brain function diseases, that is, visual stimulus, auditory stimulus, and olfactory stimulus are given to the subject, and the apex latency and the apex latency obtained at that time are given. By using the amplitude as a combined measurement result, it is possible to distinguish at least Alzheimer-type dementia and Lewy body dementia, and further, schizophrenia and depression can be differentiated, so that existing clinical practice can be performed. The data can be used effectively and efficiently. That is, for Alzheimer-type dementia, Lewy body dementia, schizophrenia, and depression, when the electroencephalogram (activated electroencephalogram) when the subject is given auditory stimulation, visual stimulation, and olfactory stimulation, Since the results peculiar to the symptom are found for the time and amplitude at which the apex latency occurs, these measurement results are obtained in advance when each stimulus is given to the average elderly person. By comparing with the average value of latency and amplitude, it becomes possible to easily distinguish which disease the subject has or is at risk of developing with high accuracy.

The present invention also provides a computer program product that executes a program including such a method for identifying a brain function disease.

According to the present invention, it is possible to discriminate brain function diseases, particularly at least Alzheimer-type dementia and Lewy body dementias, and further, brain function capable of efficiently and easily distinguishing schizophrenia and depression with high accuracy. A disease identification method and a computer program product that executes a program including the method can be obtained.

The figure which shows the apex latency and amplitude of activated EEG when visual stimulus, auditory stimulus, and olfactory stimulus are given for each type of brain function disease (AD, DLB, schizophrenia, depression). The figure explaining the feature of the sleep disorder data obtained by using a sleep test mat for a subject. A diagram systematically showing the relationship between sleep disorder data obtained from subjects and illness. Waveform diagram (raw data diagram) of an example of activated EEG when a subject is given an olfactory stimulus. The perspective view which shows the whole structure of one Embodiment of an activated electroencephalogram measuring apparatus. The schematic side view which shows the main component of the activated electroencephalogram measuring apparatus shown in FIG. FIG. 5 is a schematic side view showing a state in which a subject undergoes an electroencephalogram measurement test in the activated electroencephalogram measuring device shown in FIG. The block diagram which shows the control system of the activated electroencephalogram measuring apparatus shown in FIG. FIG. 6 is a schematic cross-sectional view of a sample bottle used in the activated electroencephalogram measuring device shown in FIG. 5 and constituting the odor generating portion. The perspective view which shows an example of the sleep inspection apparatus (sleep inspection mat). The perspective view which shows another embodiment of the activated electroencephalogram measuring apparatus which can be used in the brain function disease discrimination method which concerns on this invention. (A) is a cross-sectional view of the headband shown in FIG. 11, and (b) is a schematic perspective view of a control unit (control unit) incorporated in the headband. (A) is a perspective view of an ear pad detachably attached to the ear pad shown in FIG. 11, and (b) is a side view of the ear pad to which the ear pad of (a) is attached. (A) is a cross-sectional view of the vicinity of the electroencephalogram detection unit provided on the headband, and (b) is an enlarged cross-sectional view of a main part of the electrode portion in the electroencephalogram detection unit. (A) is a plan view of the top lid of the accommodating body of the primary electrode portion constituting the electrode portion, (b) is a plan view of the bottom lid of the accommodating body, (c) is a perspective view of the bottom lid, and (d) is an electrode portion. The perspective view of the felt electrode of the secondary electrode part which constitutes. (A) is a perspective view of an odor generator showing an example of a stimulus presenting device that can be used in the brain function disease discrimination method according to the embodiment of the present invention, and (b) is attached to an odor discharge end of the odor generator. Perspective view of the cover. (A) is a cross-sectional view of an odor generator, and (b) is a side view of a main part showing a portion of an adjusting means for adjusting the angle and height of the odor generator. (A) is a plan view of the odor discharge end portion of the odor generator, and (b) is a cross-sectional view of the odor discharge end portion. (A) is a perspective view of a piezoelectric microblower constituting a discharge means provided at an odor discharge end of an odor generator, and (b) is an enlarged cross-sectional view of a main part of the piezoelectric microblower shown in FIG. Sectional drawing of an odor source (sample bottle) with a piezoelectric microblower. (A) is a schematic front view of the breathing sensor constituting the breathing detection unit shown in FIG. 11, and (b) is a schematic side sectional view of the breathing sensor. A respiratory waveform diagram of a subject measured by a respiratory sensor for explaining the odor discharge timing of the odor generator. FIG. 3 is a schematic perspective view showing a state in which the activated electroencephalogram measuring device shown in FIG. 11 is attached to a subject. A waveform diagram (time-frequency analysis diagram) of an example of activated EEG when a subject is given a different pungent odor. It is a general electroencephalogram obtained by presenting a three-point odball task to the subject. The upper row is a waveform diagram of a person with normal working memory, the middle row is a waveform diagram of a person with weak working memory, and the lower row. Is a waveform diagram of a person with abnormal working memory. Schematic block diagram of an activated electroencephalogram measuring device and a stimulus presenting device (odor generator, sound generator) connected to the activated electroencephalogram measuring device. The perspective view which shows the still another embodiment of the activated electroencephalogram measuring apparatus.

Hereinafter, an embodiment of the brain function disease discrimination method according to the present invention will be described with reference to the accompanying drawings.
The brain function disease discrimination method according to the present embodiment is configured so that various brain function diseases can be easily identified by a simple screening test. The types of brain dysfunction here primarily consider Alzheimer's disease (AD), Lewy body dementias (DLB), schizophrenia, and depression, and these diseases (4 of these). The purpose is to make it easy to distinguish between the two types (collectively referred to as brain function diseases).

Specifically, it is desirable to first perform pre-sorting using the sleep test device (sleep test mat) 100 shown in FIG. Recent studies have shown that brain dysfunction is closely associated with sleep disorders, and the sleep test device 100 is used to understand the sleep status of the subject (causing a bad sleep state). By investigating the cause and the result), it is possible to sort in advance whether or not there is a suspicion of a brain function disease. That is, when distinguishing between Alzheimer-type dementia, Lewy body dementias, schizophrenia, and depression, by first using the detection data of sleep disorders, the subject is subjected to a screening test. It is possible to reduce the burden and anxiety and improve the accuracy of discrimination.

As shown in FIG. 10, the sleep test device 100 may be configured so as to be easily portable, and for example, a non-contact / non-restraint sleep test mat 101 provided with a data processing unit is used. (Specifically, "Sleep Scan; Registered Trademark" manufactured by Paramount Bed Co., Ltd. can be used). As shown in the figure, the sleep test device 100 is used by laying it under the bed mattress 105 in the chest region of the sleeping subject 200, and is installed in the sleep test mat 101. A sensor (pressure sensor) can detect the sleep state of the subject 200 during sleep (eg, sleep onset disorder / midway awakening / early awakening, sleep phase retreat, periodic body movement, non-rem ratio reduction, etc. It is possible to detect whether or not the subject, including abnormal breathing and abnormal heartbeat, is causing sleep disorders).

By turning the switch on and leaving the sleep test device 100 laid under the mattress of the bed for a predetermined period (for example, about one week), the subject enters the bed and leaves the bed. It is possible to detect what has been done and the body movement and respiratory state of the subject during sleep. That is, since the sleep test device 100 can continuously detect the sleep state of the subject during the period laid under the bed mattress 105, the subject is analyzed by analyzing the sleep data. It is possible to grasp the sleep situation without interfering with the normal sleep of the brain, and thereby it can contribute to the differentiation of brain function diseases.

For example, as shown in FIG. 2, from the data of the sleep test device 100, the presence / absence of apnea during sleep can be known, and the cause (insomnia cause) and the result (insomnia phenomenon) causing insomnia can be known.

Specifically, if there is apnea during sleep, the person has abnormal activity including overactivity and periodic body movement during sleep, and if he / she suffers from the above-mentioned brain function disease, this Such anomalous activity is occurring. However, some of the abnormal activities that cause sleeplessness include those associated with excretory disorders (eg, bladder disorders), oral disorders (eg, oral neuropathy), and secretory disorders. Accompanied (eg, thyroid, diabetes, etc.), respiratory disorders (eg, asthma, chronic lung disease, etc.), cardiovascular disorders (eg, hypertension, heart failure, etc.), digestive disorders (For example, constipation, diarrhea, etc.), neurological / joint system diseases (for example, rheumatism), and skin diseases (for example, itching). , It is not possible to specify whether or not it corresponds to each of these individually. For this reason, by asking (inputting) the subject in advance about their health condition such as physical condition and illness history at the time of the examination, the sleep data obtained shows that the subject has abnormal activity during sleep. It is possible to exclude subjects who have abnormal activities due to causes other than brain function diseases.

In addition, the insomnia phenomenon (result) can be grasped from the data obtained from the sleep test device 100. For example, long sleep latency (difficult to fall asleep), mid-sleep awakening, early awakening, sleep phase shift (sleep time is appropriate, but sleep time is significantly different from normal), sleep efficiency is good or bad, It is possible to grasp the high and low of the non-rem ratio, objective / subjective lack of sleep, oversleep, etc.

Then, when such data on sleep were obtained from a large number of subjects and verified, it was found that it is possible to grasp whether or not there is a brain function disease to some extent. Specifically, looking at the insomnia phenomenon (results), Alzheimer's disease is characterized by a particularly long sleep phase shift and long sleep latency, and in depression, the sleep latency is particularly long and midway. It was found that the characteristic of awakening is large, and in schizophrenia, the characteristic of awakening halfway and a decrease in the non-rem sleep ratio is particularly significant. In addition, when we examined sleep overactivity (cause of insomnia), it was found that Lewy body dementia is particularly characterized by causing REM sleep behavioral disorders and periodic limb movement disorders. ..

As a result, as shown in FIG. 3, if there is a cause of insomnia (sleep overactivity; periodic body movement, etc.) and sleep apnea occurs from the sleep data obtained from the sleep test device 100, It may be Levy body dementia, and if there is insomnia and sleep apnea, it is suspected to be Alzheimer's dementia, depression, or schizophrenia. Therefore, the sleep data obtained from the screening test using the sleep test device 100 makes it possible to preliminarily sort the subjects who have a high probability of having a brain function disease. In addition, by acquiring such sleep data, it becomes easy to formulate an effective treatment and prescription policy regarding sleep.
In this case, if there is no sleep apnea symptom, it is predicted that it is a disease of respiratory organs, circulatory organs, etc., and that it is primary insomnia due to stress or the like.

As described above, for the subjects (subjects with a high probability of brain dysfunction) sorted by the sleep test device 100, for example, the activated electroencephalogram measuring device 10 shown in FIGS. 5 to 9 continues. It is possible to more accurately identify any of the brain function diseases by testing using.

Here, the configuration of the activated electroencephalogram measuring device 10 shown in FIGS. 5 to 9 will be described.
The activated electroencephalogram measuring device 10 shown in the figure determines whether or not the patient has Alzheimer-type dementia (AD), neurodegenerative dementia represented by Lewy body dementia (DLB), schizophrenia, or depression. It is a configuration that can be done.
In general, it is known that neurodegenerative dementia develops by degenerating the proteins constituting the nerve cells due to the accumulation of harmful proteins such as amyloid β around the nerve cells. Regarding the types of dementia that represent this type (mainly AD and DLB types), AD has a decrease in the ability to discriminate odors, followed by DLB, which has a decrease in the ability to sense odors, and the sense of smell. When an odor stimulus is given to an electroencephalogram, an electroencephalogram reaction occurs when the stimulus is detected. It is known that it can be grasped by time-frequency analysis of.

The apex latency is the time (ms) from the start of the stimulus output to the occurrence of a positive waveform peak (for example, P300 component) or a negative waveform peak (for example, N200 component) or the time when it occurs (for example). (See FIG. 4), and the (apical) amplitude is the magnitude (vertical axis in FIG. 4) from the baseline to each waveform peak, with the brain waves from before the start of stimulation output to the start of output as the baseline. ..

On the other hand, it is known that the quality of the function of the prefrontal cortex, which is the control tower of the brain, can be detected by working memory (also called working memory). The working memory is, for example, when calculating 17 * 5, 5 * 7 = 35 is first obtained, then 10 * 5 = 50 is obtained, and finally, when the two are totaled, the initially obtained 35 is stored. The power you are doing. The working memory presented the stimulus to the visual sense, the auditory sense, etc. by the three-point odball method (a method of presenting the stimulating component a in 70%, the stimulating component b in 20%, the stimulating component c in 10%, etc.). It is known that the activation of EEG abc can be grasped by the apex latency / amplitude change of the EEG at each stimulation.

In the activated electroencephalogram measuring device shown in FIGS. 5 to 9, the soundness of the prefrontal cortex caused by auditory stimulation by the sound generation unit (speaker, headphones, etc.) incorporated therein, and the image presentation unit (display, etc.) connected to the prefrontal cortex. It is possible to confirm the soundness of the prefrontal cortex by visual stimulation by linking with. It is generally known that DLB reduces work memory for vision and schizophrenia reduces work memory for sound. By connecting these stimulus presentation units (devices), dementia and neurological disorders (mental disorders) Information (data) necessary for differentiating brain function diseases including schizophrenia can be obtained in a multifaceted, quantitative, and objective manner.

The illustrated activated electroencephalogram measuring device 10 is further inhaled by the subject who breathes naturally so that an accurate electroencephalogram (waveform signal) can be obtained during the measurement without imposing a burden on the subject during the measurement. It has a function to accurately identify the cause of dementia by presenting a specific odor (or odor pattern) when a state is reached and measuring the brain wave activated at that time. In the present embodiment, it is difficult to determine the degree of progression of dementia by applying external stimuli for hearing and vision as described above, and measuring each activated electroencephalogram in addition to stimulating the sense of smell. Even in cases where it is difficult to discriminate brain function diseases with only one external stimulus, it has a function that can objectively provide various electroencephalogram information useful for the discrimination. In addition to the above-mentioned stimuli, the measuring device may acquire activated electroencephalograms for the sense of touch as needed.

In addition, the activated electroencephalogram measuring device 10 has a structure that is easy to handle such as transportation and installation. For example, a medical / health center operated by each local government, a regional hospital, a personal practitioner, and dementia. It is possible to easily perform screening by installing it in a facility where it is preferable to be able to distinguish between the above, for example, a license center where a driver's license is issued. Specifically, the activated electroencephalogram measuring device 10 includes a base 11 installed on an installation table 1 such as a desk, a main body 13 provided on the base 11, and various measurement elements incorporated in the main body 13. The subject 200 has a simple structure so that the test can be performed while sitting on a chair (see FIG. 7).

Hereinafter, the configuration of the activated electroencephalogram measuring device 10 will be described.
The main body 13 is configured in a box shape with an opening at the front, and a frame 15 holding various measurement elements is installed in the opening portion. The frame 15 is provided with a fixing portion for fixing the head of the subject 200, and when the head is fixed while the subject 200 is seated, the line of sight is directed to the inside of the main body 13. It is configured as follows. Specifically, the fixing portion includes a jaw fixing portion 16 and a forehead fixing portion 17, and when the subject 200 is seated, the jaw is placed on the jaw fixing portion 16 and the forehead is placed on the forehead fixing portion 17. By pressing against, the head is fixed in the seated state (see FIG. 7). The fixed portion may be any as long as the head of the subject 200 is in a fixed state, and may be configured to include either the jaw fixing portion 16 or the forehead fixing portion 17.

Further, the jaw fixing portion 16 and the forehead fixing portion 17 are movable in the height direction, and are subject to inspection by operating the operating member 18 (see FIG. 7) of the slide mechanism (details are not shown). The height positions of the jaw fixing portion 16 and the forehead fixing portion 17 can be adjusted according to the person 200.

Above the forehead fixing portion 17 of the frame 15, an arm 19 extending toward the subject 200 side is rotatably supported in the vertical direction (may be slidable), and is inside the arm 19. Is provided with an electroencephalogram detecting unit 20. Here, the brain wave detection unit 20 is applied to a portion where changes in the brain wave can be effectively measured when an external stimulus is applied, specifically, a portion called N200 or P300 where the brain wave can be detected. The electroencephalogram detection unit 20 of the present embodiment may be any of the above, with respect to the midline center (Cz) and the midline crown (Pz) of the subject 200, which is the parietal region according to the International 10-20 Law. It is configured to include an electrode member 21 having conductivity to be applied from the vertical direction and a holding portion (pedestal) 23 for holding the electrode member 21. That is, since the parietal region can measure changes in brain waves in the somatosensory area where changes are most likely to occur in discriminating dementia, the electrode member 21 is the parietal region of the subject 200 having a fixed head. It is configured to be applied to the region (Cz).

The holding portion 23 is connected to a wiring member that is electrically connected to the electrode member 21, and the weak signal (electroencephalogram signal) of the subject obtained by the electrode member 21 is an electroencephalogram measurement circuit (operation amplification circuit). It may be amplified via 25 and transmitted to an external device (such as a PC for measuring brain waves) via a communication port such as Bluetooth (registered trademark) or WiFi (signal path shown by a solid line in FIG. 8). Alternatively, it may be sent to the control unit 30 of the control device incorporated in the device for processing (signal path shown by a broken line in FIG. 8).

From the viewpoint of hygiene, it is preferable that the electrode member 21 held by the holding portion 23 is attached to the holding portion 23 so that it can be replaced for each subject 200. The material of the electrode member 21 is not particularly limited as long as it has conductivity so that an electroencephalogram signal can be detected, but the electrode member 21 is configured to have felt impregnated with physiological saline. Is preferable. As described above, in the brain wave detection unit 20, after the subject 200 fixes the head in a predetermined position, the arm 19 rotates (or slides) in the vertical direction so as to be applied to the top region thereof. The electrode member 21 held by the arm 19 abuts against the head in the vertical direction. Therefore, by forming the electrode member 21 with felt impregnated with physiological saline, the contact with the subject 200 becomes soft, and the brain wave is measured without giving pain or stress to the subject 200. It becomes possible.

The electrode member 21 is recognized even when it is in contact with only the central center (Cz) of the head of the subject 200 when an external stimulus (smell stimulus, auditory stimulus, visual stimulus) is applied. Since the activated electroencephalogram capable of discriminating the disease can be accurately acquired, the electrode device can be easily attached to the subject 200. That is, since it is not necessary to use a general 21-pole type electrode used for EEG measurement, the burden on the subject during the measurement is reduced, and it is also preferable from the viewpoint of hygiene. For the subject 200, a reference electrode 26 that causes a potential difference with the electrode member 21 is attached to the earlobe or the like in order to acquire a weak signal at the center of the midline (Cz).

The frame 15 is provided with an odor generating portion 40 that generates an odor at a position separated from the nasal cavity of the subject 200 whose head is fixed between the jaw fixing portion 16 and the forehead fixing portion 17. The odor generating unit 40 may be any as long as it discharges the odor to the lower region of the nasal cavity, and the discharged odor is smelled when the subject's natural respiration is inhaled.

The odor generating unit 40 has a guide member 41 located below the nasal cavity of the subject, an odor source (sample bin in this embodiment) 43 held by the guide member 41, and a sample bin 43 along the guide member 41. It is provided with a sample bin transport mechanism 45 that is guided and driven, and a breathing sensor 46 that detects the breathing state of the subject.

The guide member 41 is formed in a ring shape below the nasal cavity of the subject 200 along the horizontal plane, and an opening 41a is formed corresponding to the position below the nasal cavity of the subject 200. Further, a sample bin 43 is movably held along the guide member 41 on the lower surface side of the guide member 41. The number of sample bins 43 held by the guide member 41 may be one (one type), but it is preferable that a plurality of sample bins are movably held along the guide member 41. That is, it is preferable that a plurality of types of odors can be presented to the subject 200.

Here, with reference to FIG. 9, the configuration of the sample bin 43 held by the guide member 41 will be described.
The sample bin 43 is held so as to hang down from the lower surface of the guide member 41 (details of the holding mechanism are omitted), and can be moved in the directions of arrows D1 and D2 by the sample bin transport mechanism 45 provided on the frame 15. It has become. An odor used for discriminating dementia (for example, odors of menthol, curry, mandarin oranges, roses, etc.) is enclosed in the main body 43A of the sample bin 43, and the odor is odorized via a discharge portion 43B provided above the odor. Is being discharged.

In the discharge portion 43B, rectangular flat plates 43a and 43b are overlapped with the spacer 43c interposed therebetween, and the piezoelectric element 43C is attached to the flat plate (diaphragm) 43b on the lower surface side to form a space between the flat plates 43a and 43b. A diaphragm type pump that makes S function as a pump chamber is arranged. Then, by applying an applied voltage to the piezoelectric element 43C, the flat plate 43b vibrates and exerts a function as a pump, and the odor contained in the main body 43A of the sample bottle moves as shown by an arrow and is discharged. It is ejected upward through a nozzle 43d formed so as to project in the center of 43B. In this case, the sample bin 43 is placed in the nasal cavity of the subject 200 by applying a voltage to the piezoelectric element 43C while the nozzle 43d is positioned at the opening 41a of the guide member 41 by the sample bin transport mechanism 45. On the other hand, the smell is presented. Therefore, if the nozzle 43d of the sample bin 43 held in the guide member 41 is not positioned in the opening 41a, the subject 200 does not feel the odor contained in the sample bin 43 (activated EEG). Not detected).

A detection sensor (respiratory sensor) 46 for detecting the respiratory state of the subject 200 is arranged on the frame 15. The respiration sensor 46 can be composed of, for example, one that detects a temperature change of the subject 200 by a thermocouple, one that detects a bulge of the chest during respiration by a laser beam, and the like, and exhalation of the subject 200. As long as the intake can be detected, the structure is not limited to a specific structure. The detection signal from the respiration sensor 46 is transmitted to the control unit 30, and the sample bin transfer mechanism 45 and the piezoelectric element 43C are controlled based on the detection signal. Specifically, the control unit 30 has an odor generating unit (sample bin transport mechanism 45 and piezoelectric element) so that the odor is generated from the sample bin 43 when the breathing sensor 46 detects the inspiratory state of the subject 200. 43C) is controlled.

In addition to the above-mentioned odor generating unit 40, the activated electroencephalogram measuring device 10 may further include a tactile stimulating unit 50 that stimulates the tactile sensation of the subject 200. The tactile stimulating unit 50 measures whether or not an electroencephalogram responds when an external stimulus is applied to the right side and the left side of the subject 200, and the activated brain wave measuring device 10 measures the subject. The structure is such that an external stimulus is applied to the fingers of the left hand and the fingers of the right hand so that the 200 can be easily measured. That is, the tactile stimulating unit 50 is provided on the base 11, and includes a mounting table 51 on which the palms of both hands of the subject 200 are aligned and placed, and the subject 200 is placed on the mounting table 51. The pattern patterns 51a and 51b that specify the placement positions of the left and right hands are drawn. Therefore, the subject 200 is configured to be stimulated by the left and right tactile sensations and to measure the activated electroencephalogram at that time by simply placing the palm on the patterns 51a and 51b as they are.

A finger pressing device 52 that stimulates the placed index finger is housed in the mounting table 51. The finger pressing device 52 includes pins 53 and 54 that give two points of pressing stimuli to the index fingers of each hand at predetermined intervals, and the intervals between the two points of the pins can be adjusted and the surface thereof. It is configured so that it can be sunk from. The distance between the two pins 53 that press the index finger of the left hand, the adjustment of the distance between the two pins 54 that press the index finger of the right hand, and the swelling of the pins 53 and 54 are control signals from the control unit 30. It is formed by the pressing unit drive mechanism 55 based on the above.

Further, the activated electroencephalogram measuring device 10 includes a sound generating unit 60 that generates a different sound with respect to the hearing of the subject 200. The sound generation unit 60 is provided on the frame 15 and includes a pair of speakers 61 arranged so as to cover the ears on both sides when the subject 200 fixes his / her head. From the speaker 61, a sound (presentation sound) having a different scale is reported by the sound control circuit 65 based on the control signal from the control unit 30.

Further, the activated electroencephalogram measuring device 10 includes an image display unit 70 that displays a different pattern for the visual sense of the subject 200. The image display unit 70 is provided on the frame 15 and is visible to the subject 200 (in the activated electroencephalogram measuring device 10, the upper position on the back side of the mounting table 51 constituting the tactile stimulating unit 50). It is equipped with a display 71 installed in. A plurality of images (presented images) approximated by the image control circuit 75 are displayed on the display 71 based on the control signal from the control unit 30.
It is generally known that work memory for vision is reduced in DLB, and work memory for sound is reduced in schizophrenia, and by connecting these stimulus presentation devices, dementia and neurological disease (mental disease) are included. Information (data) necessary for differentiating brain function diseases can be obtained in a multifaceted, quantitative, and objective manner.

Further, it is preferable that the activated electroencephalogram measuring device 10 is provided with an odor removing unit 80 that removes the odor of the main body 13. The odor removing unit 80 can be configured by an exhaust fan 81 driven by the odor generating unit 40 every time the measurement is completed by discharging the odor, a filter 82 for removing the residual odor, and the like.

The activated electroencephalogram measuring device 10 configured as described above incorporates a power source 90 connected to external power, and each of the above-mentioned measuring elements in the main body 13 is controlled by receiving power supplied from the power source 90. It is driven according to the control program of the unit 30. Further, even if the electroencephalogram signal detected by the electroencephalogram detection unit 20 described above is transmitted to an external device (PC for brain wave measurement, etc.) via a communication port such as Bluetooth (registered trademark) or WiFi as described above. good. In that case, the subject 200 who undergoes a medical examination with the activated electroencephalogram measuring device 10 can periodically accumulate electroencephalogram data for a plurality of years, and the presence or absence of the onset of dementia and its progression It is possible to obtain more accurate diagnostic results regarding the degree. The electroencephalogram signal obtained from the subject 200 may be managed by an external device (PC for electroencephalogram measurement, etc.) connected to the activated electroencephalogram measurement device 10, regardless of whether it is wired or wireless. The activated electroencephalogram measuring device 10 may be provided with various management functions.

When acquiring the activated electroencephalogram using the activated electroencephalogram measuring device 10 having such a configuration, the subject 200 places the jaw on the jaw fixing portion 16 and presses the forehead against the forehead fixing portion 17 to press the head. It becomes measurable by fixing. Then, for example, when the activated brain wave is acquired by odor stimulation, the inspiratory state (ON) is first detected by the respiratory sensor 46 at the time when the measurement is started, and the breath of the subject 200 becomes the inspiratory state. When the sample bin transport mechanism 45 is driven, the predetermined sample bin 43 is positioned below the nasal cavity of the subject 200.

In this state, by applying an applied voltage to the piezoelectric element 43C of the sample bin 43, the odor in the sample bin 43 is discharged into the nasal cavity of the subject 200 through the opening 41a of the guide member 41, whereby the test is performed. The brain wave of the person 200 is activated, and the brain wave data at that time is acquired. The acquisition of the electroencephalogram data is performed for a predetermined time. In this case, considering that the natural breathing of a person is usually about 2.5 to 3 seconds and the inspiratory state is about 1 to 1.5 seconds, the acquisition of brain wave data is performed for a predetermined time. If about 1 second (1000 ms) is acquired from the time when the odor is presented, the activated brain wave data at the time of inspiration can be acquired. An example of the activated electroencephalogram waveform at the time of inspiration at this time is shown in FIG. The apex latency of the brain wave activated by stimulating the sense of smell appears in about 200 ms to 500 ms, depending on aging. Therefore, if the EEG data in the time range described above can be obtained, the apex latency is reached. It is possible to sufficiently acquire the data before and after.

When a predetermined time elapses after the odor is presented, the acquisition of the brain wave data is stopped, and the driving of the piezoelectric element 43C is also stopped. Subsequently, the sample bottle transport mechanism 45 is driven to retract the sample bottle 43 presented to the subject 200 from below the nasal cavity of the subject 200 to eliminate residual odor.

Then, the acquisition of the activated electroencephalogram at the time of inspiration is executed a predetermined number of times (about 10 times), and ends when the electroencephalogram data of the predetermined number of times is acquired. In this case, by acquiring the electroencephalogram data a predetermined number of times, it is possible to obtain the added average of the electroencephalograms, and it is possible to acquire more accurate data.

That is, it is conceivable that the waveform of the brain wave is affected by the external environment during the measurement of the subject 200, but by adding the data multiple times and acquiring the average data, the brain wave due to the external environment during the measurement is obtained. It is possible to obtain accurate EEG data by eliminating the displacement of.

As described above, the activated electroencephalogram obtained by stimulating the sense of smell has a peak waveform after a predetermined time from the presentation of the odor (apex latency). This apex latency is delayed to some extent by aging, but the apex latency is slower than that of the average elderly (see, for example, the delay t ₁ of the N200 component and the delay t ₂ of the P300 component in FIG. 4). Alternatively, if sufficient (vertex) amplitude is not obtained at the apex latency, it is more likely that a brain dysfunction has developed.

In the above configuration, it is preferable that the odor generating unit 40 includes a plurality of odor sources (sample bottles) containing different odors so that a plurality of odors can be randomly presented to the subject 200. For example, the shape of the waveform of the activated brain wave is determined to some extent by the type of odor to be presented, but it does not respond to a specific odor, or a waveform deviating from a specific waveform corresponding to the odor can be obtained. May have Alzheimer's disease. In particular, when the added average of the obtained waveforms is obtained, it tends to be flat in Alzheimer-type dementia. That is, by comparing the waveform corresponding to the type of odor with the normal waveform for the odor, it is possible to distinguish the type and progress of the symptom (for Alzheimer-type dementia, two odors are used. It is also possible to distinguish by performing frequency analysis).

Further, when presenting two or more kinds of odors as described above, for example, the standard odor is set to 80% and the target odor is set to about 20%, and the target odor is presented to the subject. By giving a task in advance so as to count the number of times (also called a two-point odball task), the influence of external noise can be reduced (the S / N ratio becomes high), and the same odor is intermittent. It is possible to obtain an electroencephalogram signal with higher accuracy than to obtain the summed average by presenting the signal.

Further, in the case where the aging of the brain is progressing to some extent, it is possible to determine the degree of the progress in more detail by measuring the working memory. Whether or not the working memory is functioning normally can be grasped by measuring the activated electroencephalogram based on hearing or the activated electroencephalogram based on vision.

In the above-mentioned activated electroencephalogram measuring device 10, the working memory can be measured by using the sound generation unit 60 or the image display unit 70. For example, to a subject 200 with a fixed head, two or more sounds with different scales are randomly presented from a pair of speakers 61 (to give an auditory stimulus), and a sound of a specific scale (target sound) is presented. By measuring the activated brain wave when a task (oddball task) for counting the number is given, it becomes possible to determine whether or not the working memory is functioning normally. As a specific method, in the above-mentioned Odball task, the subject is given three different scale sounds at random (about 30 times), and the number of sounds of a specific scale is counted (three-point Odball task). When the standard sound is presented at a ratio of 80%, the target sound is presented at a ratio of 15%, and the irregular sound is presented at a ratio of 5%), the subject 200 becomes focused on the target sound and becomes the target sound. When a predetermined time has passed since the sound was pronounced, the apex latency appears in the brain wave.

Specifically, a negative runout appears around 200 ms after the target sound is produced, and a positive runout appears around 300 ms. These are also referred to as N200 and P300 as described above, and by acquiring the added average of the acquired waveform data, the subject 200 can determine whether or not N200 and P300 are induced for the target sound. If these are not accurately induced (that is, the vertex latency is delayed or accelerated), it can be determined that the working memory is abnormal.

On the other hand, even if the brain wave is measured by giving a visual stimulus using the image display unit 70, it is possible to determine whether or not the working memory is functioning normally. In this case, if the three-point oddball task is presented, the task of presenting three similar images (three distinguishable images) on the display 71 and counting the number of target images is presented. Then, it can be grasped whether or not N200 and P300 are induced.

Even in the above-mentioned tactile stimulus, when two pins 53 (54) are given a two-point stimulus to the finger at a predetermined interval, but only one point stimulus is felt (erasing phenomenon). , It may be a peripheral nerve abnormality and may be Lewy-type dementia. In this case, for the subject 200, a case where two pins are maintained at a predetermined interval and a stimulus is given at two points and a case where a stimulus is given at one point are mixed, for example, a stimulus at one point. It is possible to obtain an accurate activated EEG waveform by presenting a task that causes the number of EEGs to be counted and measuring the EEG.

Furthermore, by mixing cases where stimulation is given to only one hand and cases where stimulation is given to both hands, for example, by presenting a task to count the stimulation of only one hand and measuring brain waves. , It is possible to acquire an accurate waveform. In this case, if it responds only to the stimulus of one hand (amplitude can be obtained), there is a possibility that the peripheral nerve is abnormal, and if no response is obtained to the stimulus of both hands. , May have an abnormality in the central nervous system.

In this way, it is also possible to determine whether or not dementia has developed by giving an external stimulus by the tactile stimulating portion and acquiring the activated electroencephalogram at that time. In addition, it is known that the degree of progression of dementia changes depending on whether or not nerve cells in the somatosensory area are altered, and the first alteration occurs in the olfactory part and then in the tactile part. .. Therefore, by first measuring the activated electroencephalogram based on the sense of smell and then measuring the activated electroencephalogram based on the sense of touch, it is possible to grasp the degree of progression in the case of developing dementia.

The present inventor has verified the causal relationship between each of the above-mentioned four brain function diseases and the activated EEG when stimuli related to sight, hearing, and smell are given among external stimuli in a large number of subjects. Since the results shown in FIG. 1 were obtained, we propose a method for differentiating brain function diseases based on the verification results.
Hereinafter, the causal relationship between each of the four brain dysfunctions and the activated EEG when stimuli related to sight, hearing, and smell are given will be described with reference to FIG.

Using the activated electroencephalogram measuring device 10 shown in FIGS. 5 to 9, the subject is stimulated with respect to sight, hearing, and smell (given the above-mentioned amplitude task), and is activated when the task is given. When the electroencephalogram was detected, the latency and amplitude of the subject with brain function disease were the latency and amplitude of the average elderly person who did not suffer from brain function disease, and the average value (also called the threshold). As shown in FIG. 1, it was found that there was a relative difference between latency and amplitude.
In FIG. 1, the electroencephalogram activated when the visual stimulus is applied is a downward-sloping diagonal line, the electroencephalogram activated when the auditory stimulus is applied is the horizontal line, and the electroencephalogram activated when the olfactory stimulus is applied. Is indicated by a downward-sloping diagonal line, the left bar graph indicated by the dense gland indicates the latency, and the right bar graph indicated by the sparse line indicates the magnitude of the amplitude.
Hereinafter, a specific description will be given.

(1) In the case of Alzheimer-type dementia (AD) In Alzheimer-type dementia, the latency and amplitude of the activated EEG are below the average value regardless of whether the visual, auditory, or olfactory sensations are stimulated. (In the figure, it is shown as less than about half of the average value, but there are cases where it is slightly lower than the average value and cases where it is significantly lower; the same applies hereinafter).

(2) In the case of Lewy body dementia (DLB) In Lewy body dementia, when visual and olfactory stimuli are given, the activated EEG has latency and almost no amplitude, and gives auditory stimuli. At that time, the latency and amplitude of the activated EEG were below the average value.

(3) In the case of schizophrenia In schizophrenia, when auditory stimulation was applied, latency and amplitude were hardly observed in the activated EEG. In addition, when a visual stimulus was given, the latency was in the region near the average value, but the amplitude was lower than the average value. Furthermore, when the sense of smell stimulus was given, the latency was in the region near the average value, and the amplitude exceeded the average value (with the sense of smell stimulus, the normal latency and amplitude were obtained).

(4) In the case of depression In depression, when visual stimuli, auditory stimuli, and olfactory stimuli were applied, the latency was in the region near the average value, but the amplitude was below the average value. rice field.

As described above, the delay and amplitude of the peak latency of the brain waves activated at that time by stimulating the subject's sense of sight, hearing, and smell are determined by the latency of the average elderly person.・ Compared with the average value of amplitude, if it corresponds to any of the above (1) to (4), there is some degree of Alzheimer's dementia, Lewy body dementias, depression, and schizophrenia. It is possible to distinguish with accuracy. In this case, if none of the above applies, it may be differentiated that there is no brain function disease, and if there is some agreement, it should be differentiated from observation required or a tertiary examination should be performed. May be. Further, if the measured result is lower than the average value, the above-mentioned discrimination is possible, but in order to further improve the accuracy of the discrimination, when it is lower than the average value, it is at least half or less of the average value. Occasionally, it may be differentiated from the fact that it corresponds to the symptom.

That is, in the present embodiment, the control unit 30 of the activated electroencephalogram measuring device 10 temporarily determines the apex latency and amplitude for each subject from the waveform of the activated electroencephalogram obtained when each stimulus is given to the subject 200. Record in the storage area (measurement template). Then, the control unit 30 compares the average value individual table (the average value of the latency and the amplitude of the average elderly person shown in FIG. 1) for each stimulus with the recorded measurement result according to a predetermined algorithm. However, if any of the above (1) to (4) is applicable, the differential results for Alzheimer-type dementia, Lewy body dementia, schizophrenia, and depression are derived among the brain function diseases.

For each stimulus, it is determined which type of dementia (Alzheimer's disease, Lewy body dementia, schizophrenia, depression) has a high tendency, or which type of disease is closer to it. Comprehensive evaluation (may be quantified in some cases) according to the algorithm, and whether or not the subject corresponds to Alzheimer's dementia, Lewy body dementia, schizophrenia, or depression. You may distinguish.

For example, the activated EEG data obtained from the subject is compared with the average value individual table, and if the degree of agreement for each symptom is high or far below the average value, the subject develops the symptom. It may be possible to discriminate whether the patient is present or is in progress.

As described above, in the present embodiment, the subject is subjected to a sleep test (including a medical interview if necessary) by the sleep test device 100 as a pre-sorting, and then the test by the activated electroencephalogram measuring device 10 is performed. By receiving it, it is possible to quantitatively determine whether or not the subject has (or is likely to have) Alzheimer's disease, Lewy body dementias, schizophrenia, or depression. Therefore, the doctor can make an appropriate diagnosis for the subject, and even if he / she is not a doctor, he / she can make a more accurate diagnosis by a specialized medical institution based on the discrimination result. It is also possible to encourage them to receive it.

As a method of presenting the stimulus to the subject, as described above, it is also possible to give a stimulus to the sense of touch in addition to the sense of sight, hearing, and smell, and the activated electroencephalogram obtained by the sense of touch is detected. Therefore, it is possible to improve the accuracy of discrimination.

The above-mentioned brain function disease discrimination method may be executed by incorporating a computer program product that executes a program including the method into the control unit 30 (see FIG. 8) of the activated electroencephalogram measuring device 10. , It may be executed by incorporating it into an external device separate from the activated electroencephalogram measuring device 10.

Further, as a preliminary step of the discrimination method using the above-mentioned activated electroencephalogram measuring device 10, when the sleep test device 100 shown in FIG. 10 is used for pre-sorting, the sleep data detected by the sleep test device 100 is activated. It may be transmitted directly to the electroencephalogram measuring device 10 or the above-mentioned external device, or may be transmitted indirectly. For example, the sleep detection device 100 may incorporate a known communication unit such as Bluetooth (registered trademark) or WiFi so that sleep data can be transmitted as it is to the activated electroencephalogram measuring device 10 or an external device. However, an information recording unit may be incorporated so that a recording medium (SD card or the like) can be attached to record sleep data for a certain period of time.

In the brain function disease identification method described above, a desktop-mounted type is exemplified as the activated EEG measuring device, but the following headphone type and the following headphone type are used so that the activated EEG can be measured more easily. A stimulus presentation linked to this can also be used.
Hereinafter, these configurations will be described.

First, with reference to FIGS. 11 and 26, an outline of the activated electroencephalogram measuring device 310 and the stimulus presenting device (odor generator, sound generator) connected to the activated electroencephalogram measuring device 310 will be described.
The activated electroencephalogram measuring device 310 of the present embodiment is bridged between a pair of abutting portions 305 attached to both sides of the subject's head and these abutting portions 305 and 305 to be inspected. A headband 303 mounted on a person's head, an electroencephalogram detection unit 320 provided on the headband 303 to detect an activated electroencephalogram obtained when a subject is stimulated, and an electroencephalogram 303. It is provided with a control unit 325 that controls the operation of the brain wave detection unit and the like.

Further, for the activated electroencephalogram measuring device 310, as a stimulus presenting device, an odor generating device 340 that stimulates the subject's sense of smell and a sound generating device that stimulates the subject's hearing (described above). 360 (the sound generator is integrated with the activated electroencephalogram measuring device 310) (which may have the same configuration as the sound generating unit 60) is connected. Further, by interlocking with an image presenting device (for example, a display or the like, which may have the same configuration as the above-mentioned image display unit 70) 430, it is possible to confirm the soundness of the prefrontal cortex by visual stimulation.

The activated electroencephalogram measuring device 310 is designed so that an accurate electroencephalogram (waveform signal) can be obtained at the time of measurement without imposing a burden on the subject during the measurement. As will be described later, the odor generator 340 shown in FIGS. 16 to 20 that presents an odor to a subject is configured to present a specific odor (or odor pattern) according to the respiration of the subject. Therefore, the subject is not forced to sniff. Further, since the odor discharge amount and the odor collecting bag volume (S1) are adjusted to one intake volume, no residual odor is generated. Furthermore, the number of presentations is 6 times (2 * 3 times), which avoids familiarity and contributes to shortening the measurement time. That is, a subject with impaired cognitive function can be examined without any problem.

As for hearing, the headphone-type sound generator 360 enables the presentation of stimuli with less noise, which contributes to shortening the examination time and thus reducing the load on the subject (this also applies to visual stimuli). be).

As described above, the activated electroencephalogram measuring device 310 contains the sound generator 360 and is connected to the interlocking odor generator 340, so that it is excellent in portability and mounting fixation, and the above-mentioned activation is performed. Similar to the electroencephalogram measuring device 10, for example, it can be easily used at a medical / health center operated by each local government, a regional hospital, a personal practitioner, a driver's license center, or the like to easily perform an examination.

Hereinafter, the specific configuration of the activated electroencephalogram measuring device 310 will be described with reference to FIGS. 11 to 15 and 23.
As shown in FIGS. 11 and 23, the activated electroencephalogram measuring device 310 spans between a pair of abutting portions 305 that are applied to both ears of the subject 400 and these abutting portions 305 and 305. It is composed of a so-called headphone type provided with a headband 303 that is handed over and mounted on the head 400b of the subject 400.

Each of the attachment portions 305 is connected via a connecting portion 308, and an outer band 302 is connected above the head band 303 to the connecting portion 308, and the size of the subject's head is large. The length of the attachment part 305 can be adjusted according to the above. Further, a sponge-like disposable ear pad 304 is detachably attached to each contact portion 305 so as to cover the ears of the subject 400. Alternatively, the disposable ear pad 304 may be composed of the ear pad 309 as shown in FIG. 13 (a), which is formed in a frame shape by, for example, plastic or the like, instead of the sponge, and such an ear pad 309 may be used. As shown in FIG. 13 (b), it may be attached to the sponge-shaped ear pad 304A.

As described above, each attachment portion 305 is provided with a sound generator 360 as a stimulus presenting device so as to generate a sound that gives an auditory stimulus to the subject 400. This sound generator 360 is provided on the frame constituting each attachment portion 305, and when the activated electroencephalogram measuring device 310 is attached to the head 400b of the subject 400 as shown in FIG. 22, it is covered. It comprises a pair of speakers 361 arranged to cover the ears on both sides of the examiner 400. From the speaker 361, sounds (presentation sounds) of different scales can be presented by oddballs via a control unit (control unit) 325 incorporated in the headband 303. The sound source may be presented based on the sound information stored in advance in the storage unit provided in the control unit, or may be input from an external device (for example, a personal computer) 500 and presented. May be.

In the headband 303, a brain wave detection unit 320 that detects an activated brain wave obtained when a subject 400 is stimulated (such as an olfactory stimulus or an auditory stimulus) is penetratingly supported in a substantially central portion thereof. is set up. The electroencephalogram detection unit 320 is a site where changes in the electroencephalogram can be effectively measured when the subject 400 is stimulated from the outside, specifically, the activated electroencephalogram is generated like the above-mentioned activated electroencephalogram measuring device 10. It is provided with an electrode portion 321 that is applied to a part that can be detected. That is, the electrode portion 321 of this device is crimped from the direction perpendicular to the midline center (Cz) and the midline crown (Pz) of the subject 400, which is the parietal region according to the International 10-20 Law. This provides a structure that maximizes the conductive performance of the electrode portion (for example, the electrode resistance is set to 5 Ω or less). In addition, since the parietal region where the electrode portion 321 abuts can widely measure changes in brain waves in the somatosensory area that occur when the sensory organs are stimulated, the measuring device should have a simple device configuration of only one pole. Made possible.

The control unit 325 incorporates a CPU equipped with a signal processing circuit, an electroencephalogram analysis algorithm, and various control programs. For example, the vertical dimension is 27.9 mm, the horizontal dimension is 15.2 mm, and the thickness is 2.5 mm. It is possible to utilize an algorithm having a size of about the same size, which is electrically connected to the electrode portion 321 (to be exact, the silver plate electrode 328 described later) via a short electric wiring 319. .. The control unit 325 is a movable stabilizer (not shown) separated from a fixing plate (not shown) for fixing the spring 327, which will be described later, toward the head 400b side of the subject 400 and coupled to the free end of the spring 327. ) May be provided above.

The electroencephalogram detection unit 320 includes an electrode unit 321 and a spring 327 as a means for urging the electrode unit 321 in a direction of pressing the electrode unit 321 against the head 400b of the subject 400, and the electrode unit 321 is always humidified. And it is configured as a dispose type. Here, the details of the electroencephalogram detection unit will be described.

The electrode portion 321 is electrically contacted with the primary electrode portion 321A holding the silver plate electrode 328 by being urged by a spring 327 in a direction of being pressed against the head 400b of the subject 400, and the silver plate electrode 328. It has a secondary electrode portion 321B that is in direct contact with the head 400b of the subject 400 and holds a felt electrode 323 that is impregnated with physiological saline (see (b) in FIG. 14).

In this case, the secondary electrode portion 321B is detachably attached to the primary electrode portion 321A. Specifically, for example, the secondary electrode portion 321B has a connector (not shown) for holding the felt electrode 323, and is detachably attached to the corresponding connector of the primary electrode portion 321A via this connector. That is, the secondary electrode portion 321B can be replaced for each subject 400 from the viewpoint of hygiene. The silver plate electrode 328 is electrically connected to the control unit 325 via the conductive unit 328a and the electrical wiring 319. Further, the primary electrode portion 321A has a spring guide 327A that holds the end portion of the spring 327.

Further, the primary electrode portion 321A opens the accommodating body 329 for accommodating the physiological saline solution and the accommodating body 329 when the secondary electrode portion 321B is attached to the primary electrode portion 321A to allow the physiological saline solution in the accommodating body 329. Further, it has a means for constantly infiltrating the felt electrode 323.

Specifically, the housing body 329 is formed by accommodating physiological saline in an internal space defined by attaching the top lid 322 and the bottom lid 324 above and below the tubular main body 329a, and the bottom lid 324 is formed. , As shown in FIGS. 15 (b) and 15 (c), the silver plate is slidably fitted in the housing 329 and the secondary electrode portion 321B is not attached to the primary electrode portion 321A. It has a fitting contact portion 324c that abuts on the electrode 328, and a downward protruding portion 324b that projects downward from the fitting contact portion 324c and penetrates the central through hole 328b of the silver plate electrode 328.

When the secondary electrode portion 321B is attached to the primary electrode portion 321A, the bottom lid 324 is pushed up into the housing body 329 by the upward protruding portion 323a of the felt electrode 323 abutting on the downward projecting portion 324b. , The physiological saline solution in the accommodating body 329 is formed by pushing up the gap (pushed up) between the fitting contact portion 324c and the silver plate electrode 328 through the plurality of flow holes 324a formed in the fitting contact portion 324c. It is led out to the gap S) (the derived physiological saline solution is indicated by an arrow in (b) of FIG. 14), and the physiological saline solution is impregnated into the felt electrode 323 through the upward protrusion 323a that enters the gap S). It has become like.

That is, the protruding portions 323a and 324b of the felt electrode 323 and the bottom lid 324 and the flow hole 324c together with the silver plate electrode 328 constitute the above-mentioned means for constantly impregnating the felt electrode 323 with physiological saline. Alternatively, instead of this, the saline solution may soak into the felt electrode 323 only when the electrode portion 321 is pressed against the head 400b of the subject 400 (not always). Further, the form in which the physiological saline solution penetrates into the felt electrode 323 is not limited to the above-mentioned form, and the physiological saline solution may be impregnated into the felt electrode 323 by utilizing, for example, a capillary phenomenon or the like. ..

The material of the electrode portion 321 is not particularly limited as long as it has conductivity so that an electroencephalogram signal can be detected. For example, the secondary electrode portion 321B does not need to be formed of the felt electrode 323 impregnated with the physiological saline solution, but by forming the secondary electrode portion 321B with the felt impregnated with the physiological saline solution, the application to the subject 400 can be softened. Therefore, it becomes possible to measure the brain wave without giving pain or stress to the subject 400.

When the above-mentioned electrode portion 321 is externally stimulated (smell stimulus, auditory stimulus, tactile stimulus, or visual stimulus), the electrode portion 321 is brought into contact with only the center center (Cz) of the head 400b of the subject 400. Even in the state, it is possible to accurately acquire the activated electroencephalogram capable of discriminating dementia, and the electrode can be easily attached to the subject 400. That is, since it is not necessary to use a general 21-pole type electrode used for EEG measurement, the burden on the subject 400 at the time of measurement is reduced, and it is also preferable from the viewpoint of hygiene. For the subject 400, a reference electrode (not shown) is attached to the earlobe or the like so as to generate a potential difference between the subject 400 and the electrode portion 321 when acquiring a weak signal at the center of the midline (Cz). It will be installed.

The headband 303 is supplied with power to components such as the control unit 325, and is connected to the control unit 325 of the activated electroencephalogram measuring device 310 and the device (odor generating device 340, etc.) connected to the activated electroencephalogram measuring device 310. It has a power supply unit 390A that transmits and receives various signals to and from an external device (500) such as a stimulus presenting device and a computer.

Specifically, the weak signal (electroencephalogram signal) detected by the electrode unit 321 is an external device (PC for brain wave measurement, etc.) from the power supply unit 390A via a communication port such as Bluetooth (registered trademark) or WiFi. It may be transmitted to 500. In that case, the subject 400 who undergoes a medical examination with the activated electroencephalogram measuring device 310 can periodically accumulate electroencephalogram data over a plurality of years, and the presence or absence of the onset of dementia and its progression It is possible to obtain more accurate diagnostic results regarding the degree. That is, the electroencephalogram signal obtained from the subject 400 may be managed by the external device 500 connected to the activated electroencephalogram measuring device 310 regardless of whether it is wired or wireless, and such a management function may be managed by the activated electroencephalogram measuring device. The configuration may be provided in the device 310.

The activated electroencephalogram measuring device 310 generates an odor in conjunction with this and discharges the odor toward the nasal cavity of the nose 400a (see FIG. 23) of the subject 400, and at the same time, the odor generation controlled by the odor control unit 425. It is connected to the device 340. The connection here means a relationship in which both are functionally linked regardless of whether they are wired or wireless.

Hereinafter, the odor generator 340 will be described with reference to FIGS. 16 to 20.
The odor generating device 340 has an odor generating unit main body 345 including an odor source (odor bin) 343 and a discharging means for discharging the odor from the odor source 343, and an odor that focuses the odor discharged by the discharging means. It has a blower guide (odor collector) 341 and a supply means for supplying the odor focused by the odor collector 341 toward the nasal cavity of the subject 400.

Here, the odor generating portion main body 345 has a cylindrical shape and, for example, forms a space inside through which the outside air can flow through the ventilation holes 351 and 399 (see (a) of FIG. 17). At least one (three in this example) piezoelectric microblower 365 constituting the discharge means is fixedly arranged at the odor discharge end portion 345a of the odor generation portion main body 345.

A wide bottom of the disposable odor collector 341 formed of, for example, vinyl having a substantially conical shape is detachably attached to the odor discharge end portion 345a by fitting an annular stop ring 393 from the outside. Be done. In this case, the stop ring 393 is made of metal, for example, and is magnetically and firmly fixed by a magnet 397 fixed to a corresponding mounting position on the inner surface of the odor generating portion main body 345. In the unused state where the disposable odor collector 341 is removed from the odor discharge end portion 345a, the protective cover 370 shown in FIG. 16B is provided with the odor discharge end portion in order to prevent odor leakage. It may be detachably attached to 345a.

Further, the odor discharge end portion 345a is formed of a material to which odor is difficult to adhere, and a plurality of (two in this example) ventilation holes provided in the peripheral portion thereof and the inside of the odor generating portion main body 345 communicate with the outside. It has a through hole 351 to be made to be formed, and an odor discharge hole 352 provided inside the through hole 351 in a number corresponding to the number of piezoelectric microblowers 365. Further, in each odor discharge hole 352, a blowout nozzle 343a of the sample bottle 343 as an odor source held by the corresponding piezoelectric microblower 365 is defined by the odor collector 341 in the odor collection space (S1) (for example, volume). It is positioned so as to discharge an odor toward the inside (500 ml).

The sample bottle 343 held in each piezoelectric microblower 365 contains an odor used for discriminating dementia or the like (for example, odor of menthol, curry, mandarin orange, rose, etc.) inside (for example, in this example, in this example,). One of the three sample bins 343 is odorless), and the odor is discharged through the blowout nozzle 343a provided on the upper portion thereof. Since the odor generating unit 340 has three sample bottles 343, three types of odors can be presented to the subject 400.

The supply means for supplying the odor focused by the odor collector 341 toward the nasal cavity of the subject 400 is a support member 344 fixed to the top of the cone of the odor collector 341 and the support member 344. Consists of a plurality of cannulas 342 supported by. At the time of use, each cannula 342 has its tip discharge portion located near the nostril of the subject 400 to discharge the focused odor in the odor collector 341.

As shown in FIGS. 18 and 19, the above-mentioned piezoelectric microblower 365 constituting the discharging means for discharging the odor from the odor bin 343 is integrated with the sample bin 343 and has a rectangular flat plate 343b. , 343b'is superposed with the spacer 343c interposed therebetween, and the piezoelectric element 349 is attached to the flat plate (diaphragm) 343b' on the lower surface side, so that the space S2 between the flat plates 343b and 343b' functions as a pump chamber. The pump P is configured by superimposing the upper and lower pumps P in two stages. Then, when the applied voltage is applied to the piezoelectric element 349, the lower flat plate 343b'vibrates and the pump P operates, whereby the odor contained in the sample bin 343 moves as indicated by the arrow. Then, the sample bin 343 is discharged upward into the odor collecting space (S1) via the blowout nozzle 343a. By combining the plurality of pumps P in this way, the odor discharge force can be increased.

The odor bin 343 is formed by impregnating a porous material 372 (see FIG. 20) with a sample that emits an odor and accommodating the sample substantially densely inside. When the porous material 372 is used as described above, the heat retention capacity is enhanced, vaporization is promoted, and leakage of odor can be prevented, but the present invention is not limited to this.

Further, it is preferable that the odor generator 340 has an odor removing unit for removing the generated odor. Such an odor removing unit is arranged near the exhaust fan 381 (ventilation hole 399 of the odor generating unit main body 345) driven every time the measurement is completed by releasing the odor by the odor generating device 340 ... FIG. 17 (See (a)), or a filter (not shown) for removing residual odor.

Further, the odor generator 340 has an adjusting means for adjusting its height and inclination. Specifically, as shown in FIGS. 16 and 17, the adjusting means has a base 347 and columns 348 extending vertically upward from both sides of the base 347, and the upper and lower columns formed on the columns 348. The shaft portion 358 extending from both sides of the odor generating portion main body 345 is rotatably (tilted) and vertically movable through the slit 348a extending in the direction, and the shaft portion 358 is designated with respect to the support column 348 using the positioning member 353. The height and inclination of the odor generator 340 can be adjusted by fixing the odor generator to the vertical position and the angular position. A power supply 390B capable of applying a voltage to the piezoelectric element 349 of the piezoelectric microblower 365 through wiring 359 is embedded in the base 347, and an electric line 391 for power supply extends from the power supply 390B.

Further, the activated electroencephalogram measuring device 310 includes a breathing detection unit for detecting the breathing state of the subject 400. As shown in FIGS. 11 and 23, the respiration detection unit extends from the contact portion 305 of the activated electroencephalogram measuring device 310 via the arm 307 and faces the face (particularly the mouth) of the subject 400. It is composed of a breathing sensor 346 so as to be positioned. In this case, the breathing sensor 346 is configured to be positioned in the mouth region from one abutment 305 via an arm 307, but is located from both earmuffs via a pair of arms. It may be configured to be.

Specifically, this breathing sensor 346 is configured as an infrared flap type breathing sensor, and as shown in FIG. 21, it is rotatable around a light emitting unit 381, a light receiving unit 382, and a support shaft 384. The flap 383 provided and operated (sliding) by the exhaled air 410 from the subject 400, and the flap 383 are provided and invade the optical path 388 between the light emitting unit 381 and the light receiving unit 382 as the flap 383 operates. It has a light-shielding body 385 that blocks light from the light-emitting unit 381 to the light-receiving unit 382.

According to such a breathing sensor 346, after the flap 383 is rotated upward by the exhaled air 410 and the optical path 388 is blocked, the exhaled air 410 is not supplied and the flap 383 returns downward to recover the optical path 388. Can be judged to be the beginning of inspiration.

In the activated brain wave measuring device 310, when the detection signal obtained by the breathing sensor 346 described above is transmitted to the odor control unit 425 incorporated in the odor generating device 340 and the breathing sensor 346 detects the inspiratory state of the subject 400. The odor generator 340 is controlled so that the odor is discharged to the odor. Specifically, the odor control unit 425 generates an odor so that the sample bin 343 generates an odor when the breathing sensor 346 detects the inspiratory state of the subject 400 (when the detection signal is received). A voltage is applied to the piezoelectric element 349 of the 340. Such control is performed by detecting the operating state of the flap 383 with the breathing sensor 346, and as shown in FIG. 22, the odor is discharged triggered by the transition time from the exhalation to the inspiration (the beginning of the inspiration) in the breathing waveform as shown in FIG. (The odor generating unit 340 is operated).

The respiration sensor 346 is not limited to such an infrared flap method, and includes a sensor that detects a temperature change of the subject 400 by a thermocouple, a sensor that detects a bulge of the chest during respiration by a laser beam, and the like. You can also do it.

When the information (activated electroencephalogram data) necessary for differentiating the above-mentioned brain function disease is acquired from various aspects by using the activated electroencephalogram measuring device 310 configured as described above, as shown in FIG. 23, The activated electroencephalogram measuring device 310 is attached to the head of the subject 400. Specifically, with the pair of contact portions 305 attached to both ears of the subject 400, the headband 303 is laid over the head 400b of the subject 400, and the outer band 302 is used. Adjust the length (wear it in the optimum position for the subject). As a result, the felt electrode 323 of the electrode portion 321 provided on the headband 303 abuts on the predetermined position of the head 400b, so that the electrode portion 321 is lifted against the urging force of the spring 327 (FIGS. 12 and 14). (See the broken line in (a)), the contact pressure of the electrode portion 321 with respect to the head 400b is increased, and at the same time, the felt electrode 323 is always kept moist by the physiological saline solution from the container 329.

In this state, when subsequently giving an olfactory stimulus to the subject 400, the cannula 342 of the odor generator 340 is placed near the nostril of the subject 400 while adjusting the height and inclination of the odor generator 340. Positioned (see FIG. 23) to activate the odor generator 340. Specifically, by applying an applied voltage to the piezoelectric element 349 of the sample bin 343, the odor in any one of the predetermined sample bins 343 is inspected by the cannula 342 from the odor discharge end portion 345a through the odor collector 341. It is discharged into the nasal cavity of the person 400, thereby activating the brain wave of the subject 400, and the brain wave data at that time is acquired by the brain wave detection unit 320.

When measuring the electroencephalogram data (peak latency, amplitude, etc.), for example, the air discharge presented 10 times to the subject (arbitrary discharge of odorless a and odorous b, odorous b). A task for counting the number (two-point oddball task) is given, the activated electroencephalogram when reacting to a specific odor is measured, and this electroencephalogram data is acquired in a predetermined time. In this case, the predetermined time is usually Considering that the natural breathing of a person is about 2.5 to 3 seconds and the inspiratory state is about 1 to 1.5 seconds, the above-mentioned two-point oddball presentation for the acquisition of EEG data, With 10 presentations, one presentation can be completed in 40 to 45 seconds.

This makes it possible to acquire activated electroencephalogram data relating to the sense of smell applied to the individual table as shown in FIG.

It is also possible to determine whether the subject's EEG is normal by comparing the activated EEG data (apex latency, amplitude, etc.) 1 second (1000 ms) after presentation regardless of whether it is odorless or odorous. Is. FIG. 24 shows an example of the activated EEG waveform during inspiration, for each frequency by odor (the upper curve is the component curve of a normal person predicted by the target stimulus, and the lower curve is the component curve with respect to the standard stimulus). It is a graph of the appearance amount of. Since the appearance amount for each frequency can be obtained according to the measurement result of the subject, the obtained component curve can be compared with the component curve of such a normal person to obtain the subject. It is also possible to distinguish whether or not the state of the brain wave is normal.

The apex latency of the brain wave activated by stimulating the sense of smell appears in about 200 ms to 500 ms, depending on aging. Therefore, if the EEG data in the time range described above can be obtained, the apex latency is reached. It is possible to fully compare the data before and after.

In the above-mentioned activated electroencephalogram measuring device 310 and odor generating device 340, acquisition of electroencephalogram data is stopped when a predetermined time elapses after the odor is presented, driving of the piezoelectric element 349 is also stopped, and the fan 381 is operated. Residual odor is also eliminated. After that, by continuously applying an applied voltage to the piezoelectric element 349 of another sample bottle 343, another odor ejection operation is performed as described above. Then, the acquisition of the activated electroencephalogram at the time of inspiration is executed a predetermined number of times (for example, 10 presentations are regarded as one set and one test is performed about 3 times), and the acquisition ends when the electroencephalogram data of the predetermined number of times is acquired. do. In this case, by acquiring the electroencephalogram data a predetermined number of times, it is possible to obtain the added average of the electroencephalograms, and it is possible to acquire more accurate data.

That is, as described above, it is conceivable that the waveform of the brain wave is affected by the external environment during the measurement of the subject 400, but the measurement is being performed by adding the data multiple times and acquiring the average data. It is possible to obtain accurate EEG data by eliminating the displacement of EEG due to the external environment.

Further, the activated electroencephalogram measuring device 310 can measure activated electroencephalogram data by using the sound generator (sound generating unit) 360, similarly to the activated electroencephalogram measuring device 10 described above. For example, when the subject 400 is randomly presented (given an auditory stimulus) with two or more sounds having different scales from a pair of speakers 361 provided in the working unit 5 via the control unit 325. By measuring the activated electroencephalogram, it is possible to determine whether or not the working memory is functioning normally.

The graph shown in FIG. 25 shows a general example of the waveform of the brain wave obtained by presenting the three-point odball task to the subject, and if it is an average elderly person, the standard sound and the target. While the waveforms shown in the upper row can be obtained for sounds and disturbing sounds, those with weak work memory tend to react to disturbing sounds as shown in the middle row, and those without work memory. , As shown in the lower part, the reaction of the standard sound, the target sound, and the disturbing sound tends to be small. That is, by presenting the auditory sense and acquiring the waveform of the activated EEG, it is possible to discriminate whether or not the working memory of the subject is functioning normally.

In addition, normally, a negative runout appears around 200 ms after the target sound is produced, and a positive runout appears around 300 ms. These are also referred to as N200 and P300 as described above, and by acquiring the added average of the acquired waveform data, the subject 400 can determine whether or not N200 and P300 are induced for the target sound. If these are not accurately induced (ie, the vertex latency is delayed or accelerated), it can be identified that the working memory is abnormal (this is as described above). be).

FIG. 27 is a diagram showing another example of the activated electroencephalogram measuring device. The above-mentioned activated electroencephalogram measuring device is configured in a headphone type, and has a configuration in which a sound generating device 360 is incorporated therein. It may be configured to be directly applied and attached. As described above, the activated electroencephalogram measuring device may have a simpler configuration.

Although the embodiments of the present invention have been described above, the present invention is not limited to the above-described embodiments, and various modifications can be made without departing from the gist thereof.
For example, in the above-described embodiment, the measurement results for each subject are compared with the reference data (threshold value) of the average elderly person to distinguish each disease, but the specific comparison method is appropriately modified. can do. Further, the configuration of the activated electroencephalogram measuring device is not limited to the configuration of the above-described embodiment.

10,310 Activated EEG measuring device 100 Sleep test device

Claims (1)

The average elderly person was given each stimulus based on the measurement results obtained by measuring the apex latency and amplitude from the waveform of the activated EEG when at least visual stimulus, auditory stimulus, and olfactory stimulus were given to the subject. Compared with the average value of the peak latency and amplitude of the activated EEG obtained in advance at that time,
Regardless of whether the subject is stimulated by sight, hearing, or smell, if the peak latency and amplitude of the activated EEG are below the average value, it is differentiated from Alzheimer-type dementia.
When the visual stimulus and the olfactory stimulus were given to the subject, the apex latency of the activated EEG, and when the amplitude was not seen and the auditory stimulus was given, the apex latency of the activated EEG, and If the amplitude is lower than the above average value, it is differentiated from Lewy body dementias.
When an auditory stimulus was given to the subject, the peak latency and amplitude were not seen in the activated EEG, and when a visual stimulus was given, the peak latency was in the region and amplitude near the average value. Is lower than the above average value, it is differentiated from schizophrenia.
When the subject is given a visual stimulus, an auditory stimulus, and an olfactory stimulus, the apex latency is in the region near the average value, and if the amplitude is lower than the average value, the subject is distinguished from depression. A computer program product that runs a program.

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