WO2015125262A1

WO2015125262A1 - Biological optical measurement device and biological optical measurement method

Info

Publication number: WO2015125262A1
Application number: PCT/JP2014/054102
Authority: WO
Inventors: 洋和敦森; 木口　雅史
Original assignee: 株式会社日立製作所
Priority date: 2014-02-21
Filing date: 2014-02-21
Publication date: 2015-08-27

Abstract

Provided is a method for grasping a person's mental state, such as mood or emotion, by employing a noninvasive biological optical measurement technique. Disclosed is a biological optical measurement device comprising a light-emitting unit, a light-receiving unit, a storage unit, and an input unit, wherein: a cognitive task is presented to a subject; a biological signal within the subject is calculated from the intensity of light received by the light-receiving unit; a biological reaction to the cognitive task is acquired by the input unit; and the degree of matching between the biological signal and the biological reaction against a database indicating relationships between biological signals and biological reactions stored in the storage unit is calculated.

Description

Biological light measurement device and biological light measurement method

The present invention relates to an apparatus that supports the evaluation of a subject's condition based on measurement data and performance data of a biological light measurement apparatus.

In recent years, the number of mental health disorders is increasing, and it is important to properly grasp the mental and physical health of individuals. Techniques for acquiring and managing mental and physical health conditions have been proposed so far, for example, an individual performs a cognitive task that requires memory, and obtains a reaction time from when a stimulus to be answered is presented to when the individual responds A technique for calculating and displaying a fatigue index from this reaction time is described in Patent Document 1. According to this technique, it is possible to easily grasp the degree of individual fatigue.

Also, for example, Patent Documents 2 and 3 describe methods for evaluating an individual's mental state and biological information based on a non-invasive biological light measurement technique using light having a wavelength from visible to infrared. In the biological light measurement techniques described in these documents, the light emitted from the light source is irradiated onto the subject, the light transmitted or reflected inside the subject is detected, and the blood circulation, hemodynamics, hemoglobin is detected from the detected light quantity. Convert to biological information such as concentration change. In addition, linguistic WM tasks (tasks that require phonological loops) and non-linguistic WM tasks (tasks that do not require phonological loops) that use human working memory (WM) functions are given. Measure frontal lobe activity associated with name, retention and recall. The techniques shown in Patent Documents 2 and 3 have a feature that an index (a mood index) that reflects a depressed mood is calculated based on a specific formula using the measurement results of these frontal lobe activities. In particular, Patent Document 3 has a feature that an appropriate mathematical formula is selected from a plurality of mathematical formulas prepared in advance according to the task performance (correct answer rate, reaction time) of an individual cognitive task, and a mood index is calculated. The advantages of these methods are that there is no need to induce mood changes prior to measurement, and that non-constrained and non-invasive biological light measurement techniques are used. In other words, if this method is used, it is possible to directly obtain quantitative values reflecting daily mood states that are not triggered by specific information, and to evaluate moods in mental health measures.

JP 2011-161137 A JP 2009-285000 A JP 2013-146410 A

As described above, the biological reaction measurement technology that acquires the reaction time for a cognitive task can easily give information on an individual's condition such as fatigue. However, it is possible for an individual to adjust the speed of a biological reaction such as a reaction time. For example, when an individual responds to a cognitive task, it is easy to intentionally delay in about 1 second and answer in about 2 seconds for a task that can be answered in 1 second with the current ability and state. . When a system based on biological reaction measurement technology receives such a biological reaction, determine whether the biological reaction reflects the individual's ability or condition or is intentionally modified It is difficult.

In addition, the biological optical measurement technology that visualizes the brain activity state is non-invasive and non-constrained, and can be used in a daily environment compared to large-scale brain function imaging technology. . Furthermore, this biological light measurement technique is promising as a technique for providing information on an individual's mental state such as daily mood and emotion by acquiring a biological signal for a cognitive task that requires short-term memory. However, these conventional techniques that reflect the mental state of an individual evaluate the brain function, which is a biological signal for a cognitive task. For example, as described above, when an answer to a cognitive task is intentionally delayed, There is a possibility that a biological signal reflecting the state cannot be acquired. In addition, for example, when an individual is taking medication due to mental illness or the like, the state of the brain or living body may be different from that of a healthy person, and the biological signal acquired by the biological light measurement technique is different from that of a healthy person. It is conceivable to have

As described above, in the prior art, it is a problem to avoid an intentional reaction of an individual in living body measurement and to show an index as to whether or not the individual is in a normal state.

In order to solve the above-described problems, a biological light measurement apparatus according to the present invention includes one or more light irradiating means for irradiating a subject with light and one or more lights for detecting light transmitted or reflected by the subject. A detection unit, one or a plurality of measurement points configured by one or a combination of the light irradiation unit and the light detection unit, and a display unit that presents one or a plurality of tasks to the subject, An input unit that acquires a biological reaction of the subject with respect to the subject, a calculation unit that calculates a biological signal inside the subject from the intensity of light detected by the light detection unit, and a memory that stores the biological signal The storage unit includes a biological signal and biological reaction database of a healthy person, and the calculation unit includes the database stored in advance in the storage unit and the biological body of the subject. The degree of coincidence and the relationship between the biological reaction calculates and displays on the display unit and the items.

By using the biological optical measurement device according to the present invention, it is possible to objectively quantify how well the relationship between the biological signal measured in a daily environment and the biological reaction matches with the healthy person database. It is.

The block diagram which shows the structure of the biological light measuring device which is an Example of this invention. The flowchart which shows the process of the biological light measuring device which is an Example of this invention, and a program. The figure which shows an example of the working memory subject which is an Example of this invention. The figure which shows an example of the working memory subject which is an Example of this invention. The figure which shows an example of the database preserve | saved at the memory | storage part in this invention. The figure which shows an example which graphed the database. The figure which shows the example of a display of the display part of the biological light measuring device which is an Example of this invention. The figure which shows the example of a display of the display part of the biological light measuring device which is an Example of this invention. The figure which shows the numerical formula used in the Example of this invention. The figure which shows the example of a display of the display part of the biological light measuring device which is an Example of this invention. The flowchart which shows the process of the biological light measuring device which is an Example of this invention, and a program. The figure which shows the example of a display of the display part of the biological light measuring device which is an Example of this invention. The figure which shows an example of the database preserve | saved at the memory | storage part in this invention. The figure which shows the example of a display of the display part of the biological light measuring device which is an Example of this invention.

In the present invention, attention is paid to the relationship between a biological signal and a biological reaction with respect to a cognitive task presented to an individual in a daily environment. In particular, the following new knowledge is utilized that a person being treated for a mental illness or the like changes the relationship between a biological signal and a biological reaction between individuals according to the recovery.

The inventors present multiple working memory (WM) tasks that require short-term memory to 13 subjects who are taking a leave of absence due to mental illness and undergoing training to return to work, and measure biological light. Measurement of biological signals (brain activity signals) in the prefrontal cortex using a 22-channel measurement device based on the technology and biological reactions (reaction time, correct answer rate) by the input means (game controller) were obtained. Here, as the WM task, the spatial WM task shown in FIG. 3 and the linguistic WM task shown in FIG. 4 were used. The spatial WM task in FIG. 3 will be described as an example. The subject memorizes a plurality of white square locations presented on the target screen and remembers one white square location presented on the subsequent probe screen. Answer whether or not there is a problem with the ○ and × buttons on the input means. The biological reaction of the subject acquired by the input means is the response time (for example, milliseconds) from the presentation of the probe screen until the subject presses the button on the input means, and the correct answer of the ○ × information obtained by pressing the button of the subject It is information, and the correct answer rate is calculated from correct answer information of multiple tasks. The biological light measurement technique will be described in detail in the following examples.

The inventors conducted the above measurement once a week for several months. Further, the biological signal data at each measurement point obtained in each of the spatial and linguistic WM tasks is subjected to fluctuation correction, noise processing, and the like, and after obtaining an average waveform between a plurality of task presentations, the target stimulus presentation 5 An average value of ˜3.5 seconds was defined as a brain activity value. Furthermore, the relationship between the average value of reaction time acquired by multiple presentations of WM tasks and the brain activity value was examined. As a result, in the initial stage when the subject started participating in the training, the brain activity value and the reaction time for the spatial WM task were positively correlated, especially in the 46th and 10th fields of Broadman. However, a clear correlation tendency was not obtained. On the other hand, in the state immediately before the subject finished training and returned to work, there was a negative correlation between the brain activity value and the reaction time for spatial and verbal WM tasks. This latter result confirmed that the present inventors had the same tendency as the result that the inventors measured in the past in healthy subjects. That is, the above measurement results based on the present invention show that the relationship between the brain activity value and the reaction time is different from that of a healthy person at the time when the ability necessary for returning to work is insufficient (initial stage) Since it shows a tendency similar to that of a healthy person immediately before returning, it suggests that it can be useful information indicating whether or not the state of the subject is healthy.

In the present invention, based on the above knowledge, a specific configuration and procedure of the biological optical measurement device will be described below as an example.

FIG. 1 shows a schematic configuration diagram of the biological light measurement device of the present invention. The living body light measurement apparatus according to the present embodiment includes a living body light measuring unit 100 that performs living body measurement by irradiating a subject with light and detecting light transmitted through or reflected from the subject, and presents a stimulus to the subject and the living body. A display unit 110 that displays the measurement result, a calculation unit 111 that presents a stimulus to the display unit 110 and gives various controls to the biological light measurement unit 100, and displays the biological measurement result on the analysis and display unit 110, and a calculation unit 111 An input unit 112 that receives input of various information necessary for the biological reaction and analysis of the subject to be analyzed in step 1, a storage unit 109 that stores biological measurement results and information on task presentation, and the storage unit 109 that stores the information in advance It has a database 150 of biological reactions and biological measurement results.

Here, the calculation unit 111 includes a stimulus presentation unit 111 a that presents a stimulus on the display unit 110, a measurement control unit 111 b that provides various controls to the biological light measurement unit 100, and an analysis unit that analyzes and displays the biological measurement result on the display unit 110. 111c. The biological light measuring unit 100 irradiates light of one wavelength or a plurality of different wavelengths out of wavelengths of about 600 to 900 nm with high biological permeability. In this embodiment, the biological light measuring unit 100 irradiates light of two wavelengths. Show. Specifically, the digital / analog converters 101a and 101b for converting the digital signals D1a and D1b transmitted by the measurement control unit 111b into analog signals A1a and A1b, respectively, and the analog signals A1a and A1b having different predetermined frequencies, respectively. Modulators 102a and 102b that generate light source drive signals L1a and L1b by modulation with F1a and F1b,

light sources

103a and 103b such as laser diodes and LEDs that emit light of different wavelengths based on the light source drive signals L1a and L1b, and light sources An optical mixer 105 that mixes the light emitted from the

optical mixers

103a and 103b, an optical fiber 900 that guides the light mixed by the optical mixer 105 to the subject, and the subject that is irradiated with the light guided by the optical fiber 900 The light irradiation unit 1041 and the inside of the subject out of the light irradiated by the light irradiation unit 1041 A light receiving unit 1061 that receives light that has been transmitted or reflected, a measurement point 1001 that is configured at a substantially midpoint between the light emitting unit 1041 and the light receiving unit 1061, and received by the light receiving unit 1061 and guided by the optical fiber 900. The photodetector 106 such as a silicon photodiode, avalanche photodiode, or photomultiplier that detects the emitted light, and the analog signal A2 output from the photodetector 106 are locked in at different frequencies F1a and F1b, respectively. Lock-in

amplifiers

107a and 107b that output signals A3a and A3b, and analog /

digital converters

108a and 108b that convert analog signals A3a and A3b into digital signals D3a and D3b, respectively, and transmit them to measurement control unit 111b.

In the schematic configuration described above, the biological light measurement apparatus according to the present embodiment proceeds with processing according to the flowchart of FIG. First, in step s201, under the control of the measurement control unit 111b of the calculation unit 111, the light irradiation unit 1041 irradiates the subject 800 with light, and the light receiving unit 1061 receives the light transmitted or reflected inside the subject 800. And the biological signal of the measurement unit 1001 is acquired. Next, in step s202, the stimulus presentation unit 111a of the calculation unit 111 displays one or more cognitive tasks to be imposed on the subject 800 on the display unit 110, and the biological reaction R of the subject 800 with respect to the cognitive task is displayed. The input unit 112 transmits the data to the reception analysis unit 111c. Here, the cognitive task presented on the display unit 110 is a space that records and holds the positions of a plurality of white squares included in the target stimulus, as shown in FIG. Linguistic working memory (WM) task, or linguistic WM task that remembers / holds symbols and characters that require phonological loops to be presented as target stimuli, as shown in Fig. 4, and recalls / judges with probe stimuli after a few seconds And In addition, the biological reaction R in these cognitive tasks is the time from when the probe stimulus is presented until the input of the subject 800 is received by the input unit 112 (reaction time RT), and the subject 800 received by the input unit 112. The analysis unit 111c receives the input, and the analysis unit 111c calculates the correct answer rate (% Correct) calculated based on the result of determining the correct and incorrect answers to the cognitive task. For example, when the analysis unit 111c receives the input of the subject 800 from the input unit 112 after 1650 milliseconds from the probe stimulus presentation, the analysis unit 111c records the time of 1650 milliseconds in the storage unit 109 as the reaction time RT. Further, for example, when the stimulus presentation unit 111a repeatedly presents the spatial WM task as shown in FIG. 3 five times, the analysis unit 111c repeatedly inputs the subject 800 after each task presentation at the input unit 112 (5 The response time RT is recorded in the storage unit 109, and the result of determining the correct answer and the incorrect answer from each input is recorded in the storage unit 109. The correct answer rate% Correct is, for example, if the correct answers for the four task presentations are recorded with respect to the five task presentations as described above, the analysis unit 111c reads the number of task presentations and the number of correct answers, and the correct answer rate% Calculate = 100 × (4/5) = 80%. Next, in step s203, the measurement control unit 111b ends the acquisition of the biological signal of the measurement unit 1001, and transmits the biological signal measurement result to the analysis unit 111c. Next, in step s204, the analysis unit 111c stores the biological signal measurement result in the storage unit 109. Next, in step s205, the analysis unit 111c calculates a brain activity value Act and a biological reaction R (reaction time RT and correct response rate% Correct) for the cognitive task based on the biological signal measurement result. The brain activity value Act may be calculated using the same calculation method as that described in Patent Document 2. Next, in step s206, the analysis unit 111c reads the database 150 stored in the storage unit 109. The database 150 is stored as, for example, a table 151 as shown in FIG. 5, and the brain activity value Act of a healthy person measured in the past and the biological reaction R (reaction time RT and correct answer rate% Correct) for a cognitive task. Are stored in association with each subject. The information of this table 151 can be displayed on the display unit 110 as the relationship of the brain activity value Act to the biological reaction R by the analysis unit 111c. FIG. 6 shows an example in which the reaction time RT is used as an example of the biological reaction R and the relationship between the brain activity values Act is displayed on the display unit 110. In FIG. 6, the analysis unit 111 c reads the information in the table 151 stored in the storage unit 109, plots the brain activity values Act against the reaction time RT of each subject, and linearly fits a straight line 151 F to the plot data, Curves 151U and 151L indicating 95% confidence intervals calculated statistically are calculated by the analysis unit 111c and displayed on the display unit 110, and the relationship (correlation) between the reaction time RT and the brain activity value Act in a healthy person ). Next, in step s207, the analysis unit 111c reads the table 151 which is the database 150 stored in the storage unit 109, and the information recorded in the table 151 and the brain activity calculated in step s205 are displayed on the display unit 110. The value Act and the biological reaction R are displayed. FIG. 7 is an example in which the extent to which the brain activity value Act and the reaction time RT calculated in step s205 coincide with the information recorded in the table 151 is displayed on the display unit 110. In FIG. 7, the plot 152 indicating the brain activity value Act with respect to the reaction time RT of the subject 800 calculated in step s205 is between the 95

% confidence intervals

151U and 151L calculated by the analysis unit 111c based on the table 151. Is not included. In this example, since the brain activity value Act is large and the reaction time RT is slow with respect to the healthy person database 150, the subject indicates that the behavior control and brain activity are not functioning well.

In this embodiment, the reaction time RT is described as an example of the biological reaction R displayed on the display unit 110. However, as shown in FIG. 14, the correct response rate% Correct is displayed as the biological reaction R displayed on the display unit 110. Needless to say, the configuration using the is also effective.

Next, another display example of the brain activity value Act and the biological reaction R of the subject 800 with respect to the healthy person database 150 is shown. Here, the case where the stimulus presenting unit 111a repeatedly displays the WM task as illustrated in FIG. 3 or 4 on the display unit 110 a plurality of times. At this time, for each WM task presentation, the analysis unit 111c acquires the brain activity value Act and the biological reaction R (reaction time RT and correct answer rate% Correct) of the subject 800. FIG. 8 shows a display unit that displays the brain activity value Act of the subject 800 calculated by each analysis unit 111c and the acquired reaction time RT when the stimulus presentation unit 111a presents such a WM task six times. An example plotted on 110 is shown. Here, the analysis unit 111c reads and displays the healthy person database 150 stored in the storage unit 109, and the display method is the same as in the first embodiment. In FIG. 8, the plot of the brain activity value Act against the reaction time RT of the subject 800 with six WM task presentations is a white circle symbol in the region surrounded by the broken line 152b. The broken line 152b is shown in FIG. 8 for explaining the present embodiment, but it may or may not be actually displayed on the display unit 110. Here, the analysis unit 111c calculates the barycentric values of the six plots in the broken line 152b and displays them as black circle symbols in the broken line 152b on the display unit 110. As described above, it is possible to visualize how much the brain activity value Act and the biological reaction R of each time when the cognitive task is performed a plurality of times overlap the database 150.

In addition, as shown in FIG. 8, it is possible to calculate the degree of coincidence with the healthy person database 150 using the biological reaction R and the brain activity value Act obtained each time from the subject 800 based on a plurality of cognitive task presentations. . The analysis unit 111c determines that the data in which the white circle symbol included in the broken line 152b in FIG. 8 is within the 95

% confidence intervals

151U and 151L based on the healthy person database 150 is OK_data, and the data outside the range is NG_data. At the same time, based on (Equation 1) of FIG. 9, the degree of coincidence with the healthy person database is calculated as a percentage. For example, when OK_data is 2 and NG_data is 4, the analysis unit 111c calculates the matching degree with the healthy person database 150 as 33.3% based on (Equation 1). The analysis unit 111c can store the degree of coincidence of the subject 800 calculated by (Equation 1) in the storage unit 109 in association with the measurement date. For example, as shown in FIG. 10, the analysis unit 111c reads the degree of coincidence of the past measurement date calculated based on (Equation 1) and stored in the storage unit 109, and displays the degree of coincidence on each measurement date on the display unit 110. It is possible to display in time series. In addition, when the degree of coincidence with the healthy person database 150 continuously decreases, it is possible to display a message as shown in FIG. 10, and behavior control and brain activity are not functioning well for the target person. Can be alerted as an alarm.

In addition, the living body light measurement apparatus according to the present invention shows the mood state of the subject 800 in addition to the degree of coincidence with the healthy person database 150 described in Example 3 by adopting the technique disclosed in Patent Document 2. Is possible. For example, the calculation unit 111 (including the stimulus presentation unit 111a, the measurement control unit 111b, and the analysis unit 111c) replaces the step s202 of the flowchart shown in FIG. 2 with a step s202a and a step as shown in FIG. Processing is performed in accordance with the flowchart introducing s202b. In the following, processing with the same symbols or numbers as in the flowchart of FIG. In the flowchart of FIG. 11, in step s202a, the stimulus presentation unit 111a presents the first cognitive task on the display unit 110, and the analysis unit 111c receives a biological signal acquired by the measurement control unit 111b, and then in step s202b. The stimulus presentation unit 111a presents the second cognitive task on the display unit 110, and the analysis unit 111c receives a biological signal acquired by the measurement control unit 111b. In step s205, the analysis unit 111c reads out the biological signal stored in the storage unit 109, calculates a brain activity value Act_1 for the first cognitive task, and a brain activity value Act_2 for the second cognitive task, as shown in FIG. Based on Equation 2), the mood index Mod_index displayed as a relative value is calculated, and the degree of coincidence with the healthy person database 150 is calculated by Equation 1 according to the method described in the third embodiment. Here, either the brain activity value Act_1 for the first cognitive task or the brain activity value Act_2 for the second cognitive task may be used for calculating the degree of coincidence, or both may be used. The calculation formula of the mood index Mood_index follows the calculation method of the “depression index (D_idx)” described in Patent Document 2. According to the present embodiment, the analysis unit 111c can display the degree of coincidence with the healthy person database 150 and the time series change of the mood index Mod_index on the display unit 110 as shown in FIG. 12, for example. By displaying in this way, the mood state can be visualized in addition to the relationship between the subject's behavior control and brain activity, and information useful for grasping the state of the subject can be provided.

In the above embodiment, the healthy person database 150 is exemplified as being based on a large number of subject data measured in advance. However, this database may be stored data of the individual subject. For example, FIG. 13 shows a storage unit in which brain activity values Act and biological responses R (reaction time RT, correct response rate% Correct) acquired over a plurality of days in the past for the same subject 800 are associated with each measurement date. 109 shows an example stored as the database 150p. As shown in FIG. 13, the past data of the subject 800 is stored in the storage unit 109 in advance as the database 150p, so that the analysis unit 111c is based on the data acquired in the past from the storage unit 109. The database 150p can be read and displayed as shown in FIGS. 7, 8, 10, 12, and 14 using the brain activity value Act and biological reaction R of the subject 800 newly acquired and the database 150p. According to the present embodiment, the biological optical measurement device according to the present invention accumulates data of the time when the subject 800 was healthy in the past as the database 150p, for example, thereby causing the biological reaction R of the subject 800 to occur. And the relationship between the brain activity Act and the brain activity Act can be visualized.

The distribution of the healthy person database 150 described in Examples 1 to 5 has been described mainly using a range showing a 95% confidence interval (for example, between the

curves

151U and 151L in FIG. 7), but the 99% confidence interval. Even if it is a 90% confidence interval, it is not necessary to assume a specific distribution, and information that prescribes the range of healthy individuals in the relationship between the brain activity value Act and the biological reaction R is stored in advance. 109 may be stored.

DESCRIPTION OF SYMBOLS 100 ... Living body light measurement part, 100C ... Housing | casing, 100i ... The area | region containing a light irradiation part, a light-receiving part, and a measurement point among the inner surfaces of the biological

light measurement part

100, 1001 ... Measurement point, 101a, 101b ... Digital analog converter 102a, 102b ... modulator, 103a, 103b ... light source, 105 ... light mixer, 1041 ... light irradiation unit, 1042 ... light irradiation unit, 1049 ... light irradiation unit, 106 ... detector, 1061 ... light receiving unit, 1062 ... Light receiving unit, 1069 ... Light receiving unit, 107a, 107b ... Lock-in amplifier, 108a, 108b ... Analog / digital converter, 109 ... Storage unit, 110 ... Display unit, 111 ... Calculation unit, 111a ... Stimulus presentation unit, 111b ... Measurement control , 111c ... analysis unit, 112 ... input unit, 150 ... database, 150p ... database based on accumulation of personal data, 151 ... table that is an example of database, 800 ... subject, 900 ... optical fiber,

Claims

One or a plurality of light irradiating units for irradiating the subject with light, one or a plurality of light receiving units for detecting light transmitted through or reflected by the subject, and a combination of the light irradiating unit and the light receiving unit. Measurement points, a display unit that presents a cognitive task to the subject, an input unit that acquires a biological reaction of the subject to the task, and an intensity of light received by the light receiving unit. A calculation unit that calculates a biological signal; and a storage unit that stores the biological signal;
The storage unit stores in advance a plurality of biological signal and biological reaction information for the task,
The computing unit calculates the relationship between the biological signal and biological reaction stored in the storage unit, and the biological signal and biological reaction of the subject,
The biological light measuring device, wherein the display unit displays the calculated relationship.
The biological light measurement apparatus according to claim 1, wherein the calculation unit calculates a degree of coincidence in which the biological signal and the biological reaction of the subject are included in the distribution range of the biological signal and the biological reaction stored in the storage unit. A biological light measuring device characterized by calculating.
3. The biological light measurement apparatus according to claim 2, wherein the calculation unit calculates a temporal change in the degree of coincidence acquired in the past.
The biological light measurement apparatus according to claim 1, wherein the biological signal and biological reaction information stored in the storage unit are those of a healthy person.
The calculation unit defines a plurality of biological signals and biological reaction distribution ranges of the healthy person using the plurality of biological signals and biological reaction information stored in the storage unit, and the biological signals of the subject The biological light measurement apparatus according to claim 4, wherein the biological reaction calculates a degree of coincidence with the distribution range.