JP2008194453A - Optical measuring device for living body - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To measure the activity of a gustatory area by an optical measuring device for a living body. <P>SOLUTION: Proper measuring/analysis parameters are set in accordance with the brain function as target of measurement. In a case of measuring the gustatory function, the period without the brain activity as target of measurement is set not to include the period of 60 sec after start of stimulation. The period of activity analysis is set to include the period of 16 sec to 25 sec after start of stimulation to an oxygenated hemoglobin concentration variation signal, and include the period of 28 sec to 37 sec after start of stimulation to a deoxygenated hemoglobin concentration variation signal. The interval of providing stimulation is set to be 80 sec or more. In a case of measuring the gustatory function, parameter setting and display are performed for measuring physiological variation of the salivary gland in addition to the brain activity. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a living body light measuring device that measures information inside a living body, in particular, a signal due to a change in the concentration of a light-absorbing substance with light, and more particularly to a living body light measuring device that visualizes brain activity using data measured by living body light measurement. . The present invention also relates to a biological optical measurement device that visualizes not only brain activity but also other physiological changes.

  By using light having high light permeability and a light intensity peak wavelength in the visible to near-infrared region, it is possible to noninvasively measure information inside the living body. This is based on the Lambert-Beer law which showed that the logarithmic value of the measured optical signal is proportional to the product of optical path length and concentration. By developing this law, a technique for measuring a signal (hereinafter referred to as Hb signal) representing a relative concentration change of hemoglobin (Hb) in a living body has been developed. There are two types of Hb signals to be measured, “oxy-Hb” and “deoxy-Hb”, which are “oxy-Hb signal” and “deoxy-Hb signal”, respectively. Call. Using this technique, a technique for imaging Hb signals in the human cerebral cortex and imaging brain function at the same time has been proposed (Medical Physics 22, 1997-2005 (1995)). It's getting on. Since this technology cannot estimate the effective optical path length accurately, the measured Hb signal is a relative change, and is based on the data (rest data) for the period during which no target brain activity occurs. calculate. Or when measuring physiological changes other than brain activity, it calculates based on the data of "the period when the physiological change made into the measurement objective has not occurred". The basic calculation formula is shown below.

When the wavelength is λ and the time is t, and the transmitted light intensity (rest data) measured during the “period when the target brain activity is not occurring” is T (l, t), it is expressed by the following equation (1) it can.
-ln [T (l, t)] = eoxy (l) Coxy (t) d + edeoxy (l) Cdeoxy (t) d + a (l, t) + sc (l) (1)
Here, eoxy (l) and edeoxy (l) represent the molecular extinction coefficients of oxy-Hb and deoxy-Hb at the wavelength λ, and Coxy (t) and Cdeoxy (t) represent the oxy-Hb concentration and deoxy- Hb concentration, d is effective optical path length, a (l, t) is absorption other than Hb, and sc (l) is attenuation due to scattering in the living body. On the other hand, the transmitted light intensity Ts (l, t) when brain activity occurs is
-ln [Ts (l, t)] = eoxy (l) Csoxy (t) d + edeoxy (l) Csdeoxy (t) d + as (l, t) + scs (l)
(2)
It is represented by Here, the subscript “s” indicates a value during brain activity. In addition, it is assumed that the light-absorbing substance that changes during brain activity is only Hb, and absorption and scattering other than Hb are constant (a (l, t) = as (l, t), sc (l) = scs ( l)). Then subtracting equation (2) from equation (1),
-ln [Ts (l, t) / T (l, t)]
= eoxy (l) [Csoxy (t) -Coxy (t)] d + edeoxy (l) [Csdeoxy (t) -Cdeoxy (t)] d
= eoxy (l) DCoxy (t) + edeoxy (l) DCdeoxy (t) (3)
Holds. Here, DCoxy (t) = [Csoxy (t) -Coxy (t)] d, DCdeoxy (t) = [Csdeoxy (t) -Cdeoxy (t)] d, respectively, oxy-Hb signal, deoxy-Hb Defined as a signal. Since it is difficult to specify the effective optical path length d, brain activity is evaluated using these relative value signals (oxy-Hb signal, deoxy-Hb signal). Since light in the visible to near-infrared region used for measurement has different light absorption characteristics depending on the oxygenation state of Hb, the equation (3) for two wavelengths can be obtained by spectroscopic measurement of two wavelengths. This is solved as a simultaneous equation, and oxy-Hb signal and deoxy-Hb signal (DCoxy (t) and DCdeoxy (t)) are obtained.

  It is possible to simply calculate the initial value at the start of measurement (before stimulation) as resting data, but the signal may contain long-term changes unrelated to brain activity. Correction is necessary to detect the brain activity.

  The basic principle of this technology is that the local blood volume increased with the activity of human perceptual function and motor function is regarded as the change of oxy-y-Hb signal and deoxy-Hb signal, and the activity status of the brain is evaluated. In the point. Typical changes associated with brain activity are known as an increase in oxy-Hb signal and a decrease in deoxy-Hb signal. This is caused by an increase in blood flow to make up for oxygen and glucose consumed by metabolic activity associated with neural activity. The blood that increases is arterial blood containing oxygen, but the increase is excessive compared to oxygen consumption, and as a result, the oxy-Hb signal increases and the deoxy-Hb signal decreases. In addition, it is known that these blood volume changes are generally delayed by about 5 to 7 seconds from neural activity. Therefore, in the conventional research, although different stimuli and tasks are set according to the brain function to be measured, basically the same measurement paradigm and analysis method are adopted from the temporal aspect. In other words, based on the hypothesis that "the blood volume change accompanying neural activity occurs about 5-7 seconds after neural activity", the Hb signal starts to change 5-7 seconds after the stimulus presentation, and also 5-7 after the stimulation ends A method of obtaining a brain activity signal by repeating a plurality of stimulation presentations and setting a time interval between stimulations of about 20 to 40 seconds, assuming that it returns to the baseline after 2 seconds. In the analysis, the “rest period assuming no brain activity” is considered to be several seconds before stimulation and 5-7 seconds after the end of stimulation (set rest time parameter), for example, 5 seconds before stimulation. A method is used in which straight line data connecting the average value of the signal and the average value of 10 to 15 seconds after the end of stimulation for 5 seconds is used as “resting data”. In addition, even when the Hb signal is calculated based on the value before the start of stimulation (eg, the average value for 5 seconds before the stimulation), the “brain activity for the measurement purpose is Baseline correction using primary fitting or frequency filtering (for example, based on the average value for 5 seconds before stimulation and the average value for 5 seconds for 10-15 seconds after stimulation) Is done.

  In addition, when statistically evaluating the presence or intensity of brain activity, a representative value indicating the activity is required. However, conventionally, these are not dependent on the brain function to be measured, and the same time change (“ It has been calculated (for example, an average value or a peak value from 10 seconds after the start of the stimulus to the end of the stimulus) on the assumption that “the brain activity for the purpose of measurement is not occurring”).

  This technology has been shown to be capable of measuring brain functions such as vision, movement, language, and short-term memory, and is widely used in clinical and cognitive science research.

  Regarding taste, conventionally, brain function measurement using functional magnetic resonance imaging (fMRI) has been the mainstream. In this method, measurement is performed in an extraordinary environment, for example, a very small amount of taste sample is presented in a tube passed through the oral cavity while being fixed on its back in a very loud noise. In addition, Japanese Patent Publication No. 3-74572 discloses a taste recognition determination apparatus using an electroencephalograph. Further, NeuroImage 31, 796-806 (2006) describes a study on measurement of taste brain function using biological light measurement.

Medical Physics 22, 1997-2005 (1995) NeuroImage31, 796-806 (2006) Japanese Patent Publication No. 3-74572

  With brain function measurement technologies such as fMRI and EEG, it was not possible to measure the activity of the gustatory area in a natural environment due to device limitations. Similarly, the method disclosed in Japanese Patent Laid-Open No. 3-74572 requires a mechanical device that supplies a taste sample into the oral cavity, and an extraordinary function far from the function of “tasting” is measured. There was a possibility. Furthermore, in the case of electroencephalogram measurement, it was difficult to identify the active site, and it was not possible to know whether it was an activity of the gustatory area.

  On the other hand, biological optical measurement technology has the feature that it can measure natural brain functions in a daily environment without invasiveness and low restraint on subjects, so it is not limited to conventional basic research, but can be applied to various applications. Use is expected. For example, taste and olfaction are thought to be particularly affected by the environment, and the effectiveness of this technology that can measure brain function in a natural environment is considered to be high, but examples of measuring the activity of the gustatory area are reported It has not been. NeuroImage31, 796-806 (2006) focuses on the activity of the frontal lobe that works when memory and verbalize the taste, not the activity of the taste area that reflects the taste function. Although the cause is not specified, generally known activity in the gustatory area has not been detected.

  In addition to the brain function, in general, attempts to measure voluntary blood flow fluctuations and tissue oxygen saturation are common in biological light measurement, but attempts to measure the function in organs other than the brain are rare. I can't. The main reason for measuring the brain function is that a simple external stimulus (visual stimulus, auditory stimulus, cognitive task, etc.) causes a local blood flow change in a short time and is easy to detect. Other organs whose functions can be measured using the same method have hardly been studied, and the possibility of measuring the functions (physiological changes) of other organs when the parameter setting is changed is unknown.

  An object of the present invention is to realize a brain function measurement of the gustatory area under a natural environment, which has been difficult in the past, by using a biological light measurement device. Another object of the present invention is to realize a physiological change measurement that reflects the taste function in addition to the brain function.

  In the conventional biological light measurement device, various brain functions (vision, movement, language, etc.) have been measured and analyzed by the same method. However, the present inventor has found that the activity signal of the gustatory area changes with time differently from other typical activity signals. The present invention provides a living body light measuring device having a function capable of measuring a special activity signal in this gustatory area, and solves the above problems. Further, the present inventor has found that physiological changes of salivary glands reflecting the taste function can be measured by light. The present invention solves the above-mentioned problems by providing a biological light measurement device capable of evaluating not only brain function activity signals but also physiological changes reflecting salivary gland functions to evaluate taste functions.

  First, I will explain the peculiarities of the activity signal of the gustatory area. FIG. 1 shows typical activity signals of the motor area, visual area, and taste area. For both functions, the stimulation period is 24 seconds, finger movement tasks in motor area measurement, visual stimuli in which the red and black lattice pattern switches at 8 Hz in visual area measurement, and 15 ml sucrose aqueous solution in taste area measurement. It was given as an oral stimulus. The motor and visual cortex activity signals are similar, and the oxy-Hb signal begins to increase immediately after the start of stimulation, reaches the maximum value in about 10 seconds, and maintains that value during the stimulus presentation period. After completion of stimulation, the oxy-Hb signal starts decreasing in 0-5 seconds, and returns to the original baseline in about 5-15 seconds. The deoxy-Hb signal, which decreases on the contrary to the Oxy-Hb signal, is characterized by a time delay similar to the Oxy-Hb signal, although it is characterized by the start of the decrease and the time until reaching the minimum value. Shows the pattern and returns to the original baseline within 15 seconds after the end of stimulation. On the other hand, the activity signal of the gustatory area showed a different temporal change pattern. The oxy-Hb signal begins to increase immediately after the start of stimulation, and it takes about 20 seconds to reach the maximum value. In addition, it took about 60 seconds for the oxy-Hb signal to return to the baseline after the completion of stimulation, and it was found that the attenuation was about three times slower than in the motor and visual areas. As for the deoxy-Hb signal, it takes about 60 seconds from the end of stimulation in the same way as oxy-Hb until it reaches the minimum value after about 30 seconds from the start of stimulation and returns to the baseline.

  FIG. 2 is a diagram showing the activity signal waveforms of the motor area, visual area, and taste area on the same coordinate axis. From FIG. 2, it can be seen that the activity signal waveform of the gustatory area is not only the time scale, but also the magnitude of the signal change is significantly different from the activity signal waveforms of the motor area and the visual cortex. The activity signal waveform of the gustatory area has a change amount several times that of the activity signal waveform of the motor cortex or visual cortex, so that the signal can be detected even without the addition average that has been required conventionally. In addition, since this signal is extremely large, it may be mistaken for an artifact caused by body movement or muscle movement in the conventional analysis.

  Furthermore, as shown in FIG. 3, it has been found that the activity signal in the gustatory area shows almost the same activity waveform without depending on the stimulus presentation period. The graph of FIG. 3A shows the case where the sucrose aqueous solution is swallowed for 5 seconds and the graph of FIG. 3B shows the Hb signal when the sucrose aqueous solution is swallowed for 24 seconds. . In either case, the maximum amount of change is reached after 20-25 seconds for the oxy-Hb signal and 30-35 seconds for the deoxy-Hb signal, starting from the start of stimulus presentation (when the sucrose aqueous solution is contained in the mouth). ing. This is a phenomenon not seen in other general brain functions. For example, FIG. 4 shows an activity waveform of the visual cortex. As shown in FIG. 4A, when the stimulus presentation period is short, the maximum signal change amount is reached in about 10 seconds after the stimulus presentation, and then returns to the baseline within 10 to 15 seconds. Also, the activity intensity is small. On the other hand, if the stimulus presentation period is long, as shown in FIG. 4B, the signal change amount is maintained during that period, and returns to the baseline over 10 to 15 seconds after the stimulus presentation.

  Furthermore, the individual differences in the activity waveform of this gustatory area were found to be small. FIG. 5 shows the addition average data for 10 subjects when the sucrose aqueous solution is swallowed for 5 seconds. 5A shows an oxy-Hb signal, FIG. 5B shows a deoxy-Hb signal, and error bars indicate standard errors. As shown by the error bar, it can be seen that the variation between subjects is very small and shows almost the same time change. As a result of analyzing the data of 10 cases, the time from the presentation of taste stimuli to the maximum value of the oxy-Hb signal after 21.0 seconds on average (standard deviation: 2.0 seconds, range: 17.8-23.5 seconds), deoxy- The average time to reach the minimum Hb signal was 32.7 seconds later (standard deviation: 1.6 seconds, range: 29.5-35.1 seconds).

  Further, as shown in FIG. 19, not only the head but also the periphery of the ear was measured, and as a result, a similar Hb signal change was also observed around the cheekbone. Here, a plurality of small graphs shown in FIG. 19 are changes in the Hb signal obtained by measuring the periphery of the ear shown above at intervals of 2.1 to 3.0 cm. Although the waveform varies depending on the location, the largest change is particularly seen around the front of the ear (circle). This is thought to be a physiological change related to the salivary gland (parotid gland) rather than a signal of brain activity. As shown in FIG. 20, the temporal change of the Hb signal seen in the vicinity of the cheekbone almost coincides with the activity waveform of the taste area (brain).

  The present invention provides a living body light measurement device that sets and displays an appropriate measurement method and analysis method according to the brain function to be measured, based on the knowledge that the activity signal in the gustatory area is special. For example, when “taste” is selected as the brain function to be measured, a stimulus presentation interval of 80 seconds or more is presented and / or executed by any means, and a brain region called the gustatory area (the valve front of the lower frontal gyrus and the triangle) Hb signal of the area centered on the part), in the oxy-Hb signal, the average value or maximum value including an arbitrary period from 16 seconds to 25 seconds after the stimulus presentation, deoxy-Hb signal from 28 seconds after the stimulation The brain of the gustatory area, which has been difficult in the past, has been difficult with a biological light measurement device that calculates and displays the intensity of activity or the statistical significance of the Hb signal using the average or minimum value including an arbitrary period of up to 37 seconds as an activity index. The activity signal can be measured.

  Further, in the present invention, the biological light measurement device that sets and displays an appropriate measurement method and analysis method according to the physiological function to be measured, utilizing the knowledge that the taste function can be measured by the physiological change related to the salivary gland I will provide a. Also in this case, the stimulus presentation interval of 80 seconds or more is presented and / or executed by any means, and the Hb signal in the vicinity of the salivary gland is measured. With the oxy-Hb signal, any stimulus from 16 seconds to 25 seconds after the stimulus presentation Calculate the activity intensity or statistical significance of the Hb signal using the average or maximum value including the period, and the deoxy-Hb signal using the average or minimum value including any period from 28 to 37 seconds after stimulation as the activity index. And the display of the taste makes it possible to measure the taste function.

  According to the present invention, a brain activity signal of the gustatory area that could not be measured by the conventional method can be measured with high sensitivity. Moreover, by measuring physiological changes related to the salivary glands, the taste function can be evaluated in a multifaceted manner. Since a brain activity signal that is several to 10 times larger than that of the brain activity signal measured by the conventional biological light measurement device can be obtained, the required number of addition averaging is greatly reduced compared to the conventional art. Since it is possible to evaluate the brain activity associated with natural eating and drinking (natural movement, amount, taste), which could not be done with other brain function measuring devices, more practical and accurate evaluation of taste function is possible. In addition, the present invention can be applied to a diagnosis and treatment support tool for taste disorders, or development and evaluation of beverages and foods.

  Embodiments of the present invention will be described below.

[Example 1]
A basic mode for carrying out the present invention will be described with reference to FIG. 6, FIG. 7, FIG. 10, and FIG. 6, 7, 10, and 12 are common block diagrams showing an outline of the biological light measurement device according to the present invention.

  The biological light measurement unit is composed of a control device 602 composed of an electronic computer typified by a personal computer or a workstation, two laser diodes 608 and 609 having peak wavelengths at different wavelengths, and the two laser diodes differently. Oscillators 606 and 607 that generate a signal to be modulated at a frequency, an optical mixer 610 that mixes two lights having different peak wavelengths, and light from the optical mixer 610 on an object via an optical fiber 612 A light irradiating means for irradiating the light irradiating position; a light detector 611 for detecting mixed light from the light detecting position (a point about 3 cm away in the present embodiment) that is appropriately separated from the light irradiating means via the optical fiber 613; The lock-in amplifiers 604 and 605 to which the modulation frequency from the oscillator is input as a reference signal and the transmitted light signal of each wavelength band, which is the output of the lock-in amplifier, are changed from an analog signal to a digital signal. Comprising a digital converter 603 - analog. The approximate midpoint between the light irradiation position and the light detection position is taken as the center of the measurement position.

  6, 7, 10, and 12 show a case where there is only one light irradiation position, a light detection position, and a measurement position. Actually, a plurality of light irradiation positions and light detection positions are alternately displayed. It is possible to set a plurality of measurement positions. In this apparatus, since a plurality of optical signals are separated using an oscillator, it is possible to measure optical signals from a plurality of positions even with a single detector. In this embodiment, a plurality of optical signals are separated using an oscillator, but it is also possible to separate optical signals at lighting timing using pulsed light without using an oscillator.

  The transmitted light signal of light in each wavelength band is input to and stored in the control device 602 after being converted from analog to digital by the analog-to-digital converter 603. The control device 602 calculates each Hb signal at each measurement site based on the transmitted light signal and stores it together with the original signal (transmitted light signal). The method for calculating the Hb signal from the transmitted light signal is described in detail in Medical Physics 22, 1997-2005 (1995). In the present embodiment, the control device 602 is described as performing both measurement control and data storage / analysis. However, the control device and the analysis device may be separately performed on different PCs.

  The control device 602 has characteristics different from those of the prior art in two functions of a measurement method presentation function and a data analysis function.

(Measuring method presentation function)
First, the presentation function of the measurement method will be described with reference to FIGS. 6 and 7. First, the measurer selects a brain function to be measured on the display screens 601 and 701. FIG. 6 (display screen 601) shows an example in which “taste” is selected by a radio button, and FIG. 7 (display screen 701) shows an example in which “visual / others” is selected by a radio button. Note that the illustrated graphical user interface is merely an example, and the present invention is not limited to this form.

In the “taste” measurement in FIG. 6, radio buttons for specifically selecting the type of taste to be presented next are displayed. When sweet taste is selected as the taste to be presented, the next measurement parameter list is displayed. First, the minimum necessary measurement area centered on the temple cover, which is known as the primary gustatory area, covers the island, etc. is displayed. An example of a measurement interface that covers this measurement area is shown in FIG. Headphone type 801, hair band type 802, and eyeglass type 803 are shown as probe caps specialized in the measurement of the taste area. Both are designed to measure the vicinity of the temple with a primary gustatory area, and are characterized by shapes that do not interfere with natural “drinking” and “eating” movements. Furthermore, in the list of measurement parameters on the display screen 601, a stimulus presentation method such as an appropriate concentration of a sweet sample (concentration of an aqueous solution such as glucose, sucrose, sugar, artificial sweetener, etc.), a single presentation amount, a presentation interval, and the number of presentations. Is displayed. In taste measurement, the most clearly different parameter from other function measurements is the stimulus presentation interval. As shown in FIG. 1 and FIG. 2, the activity signal of the gustatory area takes about 80 to 90 seconds to return to the baseline value (when the stimulus presentation start time is 0 seconds), so the presentation interval is “80”. More than a second. " Further, since the amount of signal change is several times larger than that of the conventional brain activity signal (FIG. 2), the number of repeated presentations of the same stimulus may be small. Here, “2 times or more” is displayed, but it is possible even once. These measurement parameters are stored in the memory of the control device 602, and are displayed as default values on the display screen 601 when the taste is selected as the measurement brain function.

  When the taste function is selected, parameters for measuring physiological changes related to salivary glands can be displayed in addition to the parameters for brain activity measurement, as shown in FIG. The parameters displayed on the display screen 2102 at this time are basically the same as the parameters for brain activity measurement shown in FIG. 6 except that a region covering the salivary gland is displayed instead of the gustatory area as the display of the measurement site. It is. FIG. 22 shows an example of a subject interface that covers the measurement region, which is used when the measurement site is the salivary gland. Here, a headphone type is shown as a probe cap specialized in salivary gland measurement. This is an effective shape for measuring the vicinity of the cheekbone with the parotid gland.

  In addition to displaying the measurement parameter list on the screen as in the present embodiment and assisting the measurer to perform, the measurement parameter list is input as a parameter to the stimulus presentation system and the actual stimulus presentation is executed. It is also possible. For example, the function of presenting stimulus presentation timing (taste sample intake timing) as an image or sound according to the measurement parameters advances measurement automation and reduces the burden on the measurer. FIG. 9 shows a conceptual diagram of a fully automated taste function measurement system. An optical fiber 901 is connected to a measurement box 902 from a headphone probe holder 904 configured to measure a taste area worn by a subject, and the measured transmitted light data is recorded. The measurement box 902 may be attached to the subject, but can be integrated with the measurement chair 903. The measurement box 902 or the measurement chair 903 integrated with the measurement box has a function capable of communicating with the biological light measurement device main body 905 by wire or wirelessly. The biological optical measurement device main body 905 performs all of the execution of the measurement paradigm, storage of the measurement signal, analysis, and display of the results. For example, the taste sample to be presented next can be presented directly in the cup 906 with the set taste, amount and timing. The subject can know the activity signal of his / her taste area with an image, a graph, a numerical value, etc. after ingesting the presented beverage at the presented timing and method.

  It should be noted that this taste function measuring system can be used in the same manner when the taste function is measured by a physiological change related to the salivary gland instead of the taste area.

  In the example of FIG. 7 (display screen 701) in which “visual / other” is selected as the measurement brain function, the brain function to be measured is specifically selected from the pop-up menu. Since “sight (checkerboard)” is selected here, the occipital lobe responsible for the visual function is displayed as the measurement site. Further, as a detailed presentation method of the checkerboard stimulation, a switching speed, a presentation time, a presentation interval, a number of presentations, and the like are displayed. Even when “visual / others” is selected, these measurement parameter lists can be input to the stimulus presentation system as setting parameters and used for actual stimulus presentation. When “visual / other” is selected, a brain function measurement method using a conventional biological light measurement device is employed. The main difference from the parameters in the gustatory area measurement is that the presentation interval of 20 to 60 seconds is sufficient, and the signal intensity is small, so the number of repeated presentations is 3 times or more (in the example of the figure to 5 times) Setting) This is a necessary point.

(Data analysis function)
Next, the data analysis function will be described with reference to FIG. 10, FIG. 11, FIG. 12, and FIG.
10 and 11 show data analysis examples when “taste” is selected as the measurement function. First, in order to set the range of data analysis centered on the stimulus presentation period, the "pre-stimulation" period, the "post-stimulation" period, and the "relaxation" period are set. There is a need (see FIGS. 11 and 13). The pre-stimulation period is a pre-stimulation period to be examined in order to see changes due to the stimulus, and the length is not particularly limited. However, when repeatedly presenting stimuli, changes due to the previous stimulus may remain depending on the length of the stimulus presentation interval, so it is desirable to set it as short as possible (usually 1 to 10 seconds). Seconds). In this case, set “5 seconds”. The next post-stimulation period is an important parameter in the present invention. This represents the analysis period after the end of stimulus presentation. As shown in Fig. 1 and Fig. 2, the activity of the gustatory area takes 80 to 90 seconds from the start of stimulus presentation, so it must be set longer than other brain functions. There is. Here, since the stimulus presentation period is 24 seconds, a post-stimulation period of 60 seconds was set (presentation interval of 84 seconds when the stimulus presentation start is used as a reference). The relaxation period is used to remove a long-term fluctuation component that changes without depending on stimulus presentation. For example, the primary fitting is performed based on the average value of the pre-stimulation period and the average value of the post-stimulation period excluding the relaxation period, and the baseline correction is performed. In order to eliminate the period in which the signal change remains as much as possible, “50 seconds” is set here. In some cases, baseline correction is performed using frequency filtering (cutting low frequency components) based on the entire time including the period before stimulation to the period after stimulation. It is also possible to simultaneously measure brain activity signals other than the gustatory area, such as motor area activity caused by the “drinking” action, and correct the brain activity signal based on the intensity of the activity. Furthermore, in the measurement of the gustatory area, it has been observed that the response to the stimulus given to the first time becomes extremely large, and it is effective to use the first response for the analysis. Conversely, it is also possible to evaluate the sensitivity to taste by evaluating only the first activity signal.

  FIG. 10 further displays a parameter setting screen for evaluating changes in the Hb signal due to stimulation. Here, an analysis activity period is set as an example. The analysis activity period is for evaluating the presence or intensity of the activity based on the signal change amount in this period, and it is necessary to set the activity period having the most reliability and validity. As shown in FIG. 5, in the average taste area activity signal, the time from the presentation of the taste stimulus to the maximum value of the oxy-Hb signal after an average of 21.0 seconds (standard deviation: 2.0 seconds, range: 17.8 to 23.5) ), The time to reach the minimum value of the deoxy-Hb signal was 32.7 seconds on average (standard deviation: 1.6 seconds, range: 29.5-35.1 seconds). The period from second to 25 seconds and the period from 28 seconds to 37 seconds after the start of stimulation were set as an example of the analysis activity period in the deoxy-Hb signal. For example, the average value or peak value in the analysis activity period, or the result of statistical analysis such as t-test or variance analysis using them is displayed on an activity map or the like. Alternatively, a method for evaluating the activity based on the typical activity waveform shown in FIG. 5 is also effective. In this case as well, the general hemodynamic function used in fMRI analysis cannot detect the activity signal of the gustatory area discovered by the inventors, so the oxy-Hb signal is 16 to 25 seconds after the start of stimulation. In the deoxy-Hb signal, a polynomial function as shown in FIG. 5 showing the minimum value in the period from 28 seconds to 37 seconds after the start of stimulation is used as the reference waveform. As the reference waveform, a template waveform theoretically created from a research example, an average waveform created from a database storing actual data, or the like is used. In addition, depending on the data to be analyzed, data obtained by appropriately filtering those waveforms is used. Using these reference waveforms, correlation analysis and analysis using a general linear model are performed. Furthermore, since the activity waveform of the gustatory area has a characteristic that the decay from the peak is slower than that of other brain function activity signals, the activity can be evaluated using the time constant of the decay curve (definition example eu * t) as an index. Is possible.

  The analysis result is indicated by, for example, an activity map or an activity waveform. In addition to a simple signal change amount, a statistical value represented by a t value, F value, p value, etc., a time constant of an attenuation curve, a correlation coefficient, and the like can be used for the activity map. Of course, not only parametric analysis but also non-parametric analysis can be used. In addition, the activity representative waveform indicates a waveform at one measurement point where the activity appears most noticeably, or an average waveform at a plurality of measurement points in the activity region. In these cases, comparison is facilitated by a method in which “reference data” indicating a predicted result and “actual data” actually measured are displayed side by side. As the “reference data”, average data of the same subject measured so far, average data between subjects, ideal activity data theoretically derived, or the like can be used.

  FIG. 23 shows a parameter setting screen for data analysis when the taste function is measured by physiological changes related to the salivary glands. In the pre-stimulation period, the post-stimulation period, the relaxation period, and the analysis activity period, almost the same parameter values are set for the same reason as that for analyzing the function of the gustatory area described above. For example, the analysis activity period is set to include a period from 16 seconds to 25 seconds after the start of stimulation for the oxygenated hemoglobin concentration change signal, and after the start of stimulation for the deoxygenated hemoglobin concentration change signal. It is set including a period from 28 seconds to 37 seconds. The presence / absence or intensity of physiological change is evaluated by the average value or the maximum value of the oxygenated hemoglobin concentration change signal or the deoxygenated hemoglobin concentration change signal during this analysis activity period. The analysis parameter includes physiological change reference waveform data for evaluating the presence / absence or intensity of physiological change, and the reference waveform data for the oxygenated hemoglobin concentration change signal is a period from 16 seconds to 25 seconds after the start of stimulation. The reference waveform data for the deoxygenated hemoglobin concentration change signal is a polynomial function having a minimum value in a period from 28 seconds to 37 seconds after the start of stimulation.

  In order to compare with the analysis method of the gustatory area measurement, FIGS. 12 and 13 show data analysis examples when “visual / others” is selected as the measurement function. The main difference between the two is the pre-stimulation period, the relaxation period, and the analysis activity period, which is due to the difference in the activity signal waveform. As shown in FIG. 1 and FIG. 4, in the activity of the visual cortex, the oxy-Hb signal begins to increase immediately after the start of stimulation, reaches the maximum value in about 10 seconds, and after the end of the stimulus presentation, it reaches 0 to 5 seconds. It starts to decrease and returns to the original baseline within 15 seconds after the end of stimulation. Also, the deoxy-Hb signal, which decreases on the contrary to the Oxy-Hb signal, has a characteristic that the start of the decrease is slightly slow, but basically shows a similar time-varying pattern within 15 seconds after the end of stimulation. Returns to the original baseline. Therefore, the post-stimulation period and the relaxation period should be 20 seconds and 15 seconds or more, respectively, and it is sufficient for normal cases. As for the analysis activity period, based on the activity waveform of the typical visual cortex shown in Fig. 1, the period from 10 seconds after the start of stimulation to 8 seconds after the end for the oxy-Hb signal, the stimulus for the deoxy-Hb signal An example of setting a period from 15 seconds after the start to 8 seconds after the end is shown.

  The features of the “Measuring method presentation function” and “Data analysis function” explained above have a database of “measurement parameters” and “analysis parameters” corresponding to the brain function to be measured. is there. This database is stored in the memory of the control device 602. FIG. 14 shows an example of storing various parameters. When the measurer sets the brain function to be measured and its specific stimulus, parameters suitable for each stimulus are provided.

  It should be noted that the data stored in the database as measurement parameters and analysis parameters for brain function measurement regarding the taste can be applied as they are when the taste function is measured by physiological changes related to the salivary glands.

[Example 2]
In Example 2, a taste measurement apparatus using the biological light measurement apparatus of Example 1 is shown. FIG. 15 shows an example of a screen on which the taste sensitivity for “sweetness” is measured. The display items include the characteristics (taste, concentration, amount, etc.) of the currently presented sample, the measured gustatory field activity (activity waveform of the Hb signal, activity site, etc.) and reference data for evaluating taste sensitivity. Comparison, characteristics of sample to be presented next (taste, concentration, amount, etc.), graph showing taste sensitivity of subject, and the like. Here, in order to accurately measure the taste sensitivity, an example is shown in which the taste sensitivity is evaluated according to the difference between the taste field activity for the current sample and the reference data. The taste sensitivity can be evaluated using, for example, a difference between peak values compared to reference data and a relative value based on a correlation coefficient with reference data. In addition, as shown in the flowchart of FIG. 17, the next sample to be presented is determined according to the difference between the current taste area activity (Hb signal) and the reference data, and until the measured taste area activity approaches the reference data, It is possible to evaluate the accurate taste sensitivity by repeating the work. Here, only the oxy-Hb signal is displayed as the gustatory area activity, but a deoxy-Hb signal or a total-Hb signal that is the sum of the oxy-Hb signal and the deoxy-Hb signal may be used.

  Such taste sensitivity measurement is possible for each of the five basic tastes consisting of “sweet”, “salt”, “acid”, “bitter”, and “umami”. By executing these taste sensitivity measurements in order, the overall taste sensitivity can be finally evaluated as shown in FIG. In FIGS. 15 and 16, not only taste and taste area activity (Hb signal), but also frontal lobe activity (Hb signal) related to subject's subjective evaluation and taste evaluation are simultaneously measured, thereby enabling more accurate taste sensitivity. Can be evaluated. For example, a two-dimensional subjective evaluation table as shown in FIG. 18 is prepared in front of the subject, and after the presented taste sample is drunk, the container is placed in the corresponding cell. Then, how the subject feels about the taste can be evaluated on two axes, the axis of “sweetness” and the axis of “like-dislike”. This subjective evaluation result and brain activity measurement result can be combined to evaluate not only taste sensitivity but also subject's subjective taste preference. In addition, by making the subjective evaluation table of FIG. 18 an electronic device equipped with a pressure sensor, it is possible to automatically input the evaluation result to the analyzer, and at the same time, the weight is measured and the subject drank. It is also possible to automatically measure and record the amount.

  Here, the taste measurement device using the biological light measurement device for measuring the gustatory area has been described, but the same taste measurement device can also be used by using the biological light measurement device for measuring the taste function due to physiological changes related to the salivary glands. Can be built.

  The taste measurement apparatus shown in the present embodiment enables diagnosis support for taste disorders and rehabilitation support thereof. Taste disorder is a disease that affects about 14 people in 10,000 people, and diagnosis has to rely on patient's subjective reports, so the effectiveness of this taste measurement device is high. On the contrary, in occupations (drink panelists, sommeliers, etc.) that need to increase the taste sensitivity, this apparatus can be used as part of taste training or taste test.

  On the other hand, when information on the preference of the subject is used, it can also be used as a tool for supporting the development of beverages and foods. It is also useful for the development of beverages and foods for infants and pets who cannot report taste preferences.

The figure which shows the typical activity Hb signal in each of motor area, visual cortex, and gustatory area. The figure which shows the typical activity Hb signal in the motor cortex, visual cortex, and gustatory area shown on the same scale. The figure which shows the activity Hb signal of the gustatory area in a different stimulus presentation period. The figure which shows the activity Hb signal of the visual cortex in a different stimulus presentation period. It is a figure which shows the average taste field activity signal of 10 test subjects, (a) is an oxy-Hb signal, (b) is a figure which shows a deoxy-Hb signal. The block diagram which shows the apparatus structure of one Embodiment of this invention. The block diagram which shows the apparatus structure of one Embodiment of this invention. The figure which shows the example of the test subject interface (measurement probe holder) for performing taste field measurement. The conceptual diagram of a fully automatic type taste function measuring system. The block diagram which shows the apparatus structure of one Embodiment of this invention. The figure which shows the example of a gustatory field Hb signal. The block diagram which shows the apparatus structure of one Embodiment of this invention. The figure which shows the example of a visual cortex Hb signal. The figure which shows the example of the various parameters corresponding to a brain function and a measurement stimulus. The figure which shows the example of a display screen of a taste measurement apparatus. The figure which shows the example of a display screen of a taste measurement apparatus. The flowchart which shows an example of the taste sensitivity evaluation processing method in a taste measurement apparatus. The figure which shows the example of the two-dimensional subjective evaluation table | surface regarding taste. The figure which shows the physiological change data reflecting the salivary gland function. The figure which compared and showed the activity waveform of Hb signal seen near the cheekbone and the gustatory area (brain). The figure which shows the example of a measurement parameter input screen for taste function measurement. The figure which shows the example of the test subject interface which covers a measurement area | region. The figure which shows the example of the parameter setting screen for data analysis.

Explanation of symbols

601 ... Display unit, 602 ... Control device, 603 ... Analog / digital converter, 604 ... Lock-in amplifier, 605 ... Lock-in amplifier, 606 ... Oscillator, 607 ... Oscillator, 608 ... Light source, 609 ... Light source, 610 ... Optical mixer , 611 ... Optical detector, 612 ... Optical fiber for light irradiation, 613 ... Optical fiber for light detection, 701 ... Display unit, 901 ... Optical fiber, 902 ... Measurement box, 903 ... Measurement chair, 904 ... Headphone probe holder, 905 ... Biometric light measuring device body, 906 ... Presentation taste sample, 1001 ... Display unit, 1201 ... Display unit

Claims (26)

A light irradiation means for irradiating the subject's head with light;
A light receiving means for detecting passing light irradiated from the light irradiating means and propagating through a measurement point in the subject head;
An input unit for inputting the type of brain function to be measured;
Different analysis parameters are set according to the type of brain function input from the input unit, and based on the signal detected by the light receiving means, the oxygenated hemoglobin concentration change signal and the deoxygenated hemoglobin at the measurement point A calculation unit for calculating a concentration change signal;
A biological light measurement apparatus comprising: a display unit that displays a calculation result of the calculation unit.   The living body optical measurement apparatus according to claim 1, wherein the analysis parameter includes a time parameter for setting a period during which no brain activity as a measurement target occurs.   3. The biological measurement apparatus according to claim 2, wherein the brain activity targeted for measurement is set based on an elapsed time from the start of stimulation when the brain function targeted for measurement is a taste function. The living body light measurement device according to claim 1, wherein when the brain function to be measured is other than the taste function, the elapsed time from the start of stimulation and the elapsed time from the end of stimulation are set as a reference.   3. The biological measurement apparatus according to claim 2, wherein the period during which the brain activity targeted for measurement does not occur does not include a period of 60 seconds after the start of stimulation when the brain function targeted for measurement is a taste function. When the brain function for measurement is other than the taste function, it is set so as not to include the stimulation period and the period of 5 seconds after the end of the stimulation.   2. The biological optical measurement apparatus according to claim 1, wherein the analysis parameter includes an analysis activity period that is a period for evaluating the presence or intensity of brain activity.   6. The biological measurement apparatus according to claim 5, wherein when the brain function to be measured is a taste function, the analysis activity period is from 16 seconds to 25 seconds after the start of stimulation with respect to the oxygenated hemoglobin concentration change signal. A biological light measuring apparatus, which is set including a period, and is set to include a period from 28 seconds to 37 seconds after the start of stimulation with respect to a deoxygenated hemoglobin concentration change signal.   6. The biological measurement apparatus according to claim 5, wherein presence or intensity of brain activity is evaluated by an average value or a maximum value of a concentration change signal of oxygenated hemoglobin or a concentration change signal of deoxygenated hemoglobin during the analysis activity period. A biological light measurement device.   2. The biological optical measurement apparatus according to claim 1, wherein the analysis parameter includes reference waveform data of brain activity for evaluating presence or intensity of brain activity.   9. The biological measurement apparatus according to claim 8, wherein when the brain function to be measured is a taste function, the reference waveform data of the activity with respect to the oxygenated hemoglobin concentration change signal is from 16 seconds to 25 seconds after the start of stimulation. It is a polynomial function having a maximum value in a period, and the reference waveform data of the activity with respect to the deoxygenated hemoglobin concentration change signal is a polynomial function having a minimum value in a period from 28 seconds to 37 seconds after the start of stimulation. A biological light measuring device as a feature.   9. The biological light measurement device according to claim 8, wherein the analysis parameter is stored in advance in a storage unit. A light irradiation means for irradiating the subject's head with light;
A light receiving means for detecting passing light irradiated from the light irradiating means and propagating through a measurement point in the subject head;
An input unit for inputting the type of brain function to be measured;
Based on the signal detected by the light receiving means, a calculation unit for calculating a concentration change signal of oxygenated hemoglobin and a concentration change signal of deoxygenated hemoglobin at the measurement point;
A measurement unit including a stimulus presentation method and a display unit for displaying a calculation result by the calculation unit;
The living body light measuring device, comprising: displaying different measurement parameters on the display unit according to the type of brain function input from the input unit.   12. The biological light measurement device according to claim 11, wherein when the brain function to be measured is a taste function, a stimulus presentation interval of 80 seconds or more is displayed as one of the measurement parameters. .   12. The biological light measurement apparatus according to claim 11, wherein the measurement parameter is stored in advance in a storage unit. A light irradiation means for irradiating the subject with light;
A light receiving means for detecting passing light irradiated from the light irradiating means and propagated through the measurement point in the subject;
An input unit for inputting the type of physiological change to be measured;
Different analysis parameters are set according to the type of physiological change input from the input unit, and based on the signal detected by the light receiving means, the oxygenated hemoglobin concentration change signal and the deoxygenated hemoglobin at the measurement point A calculation unit for calculating a concentration change signal;
A biological light measurement apparatus comprising: a display unit that displays a calculation result of the calculation unit.   15. The living body optical measurement apparatus according to claim 14, wherein the analysis parameter includes a time parameter for setting a period during which a physiological change intended for measurement has not occurred.   16. The biological measurement apparatus according to claim 15, wherein a period during which the physiological change targeted for measurement does not occur is set based on an elapsed time from the start of stimulation when the physiological change targeted for measurement is a salivary gland function. A biological light measurement device characterized by the above.   16. The biological measurement apparatus according to claim 15, wherein the period in which the physiological change targeted for measurement does not include a period of 60 seconds after the start of stimulation when the physiological change targeted for measurement is a salivary gland function. The living body light measuring device characterized by being set to.   15. The living body optical measurement apparatus according to claim 14, wherein the analysis parameter includes an analysis activity period that is a period for evaluating the presence or absence of a physiological change or intensity.   The biological measurement apparatus according to claim 18, wherein when the physiological change to be measured is a salivary gland function, the analysis activity period is from 16 seconds to 25 seconds after the start of stimulation with respect to a concentration change signal of oxygenated hemoglobin. A biological light measuring apparatus, which is set including a period, and is set to include a period from 28 seconds to 37 seconds after the start of stimulation with respect to a deoxygenated hemoglobin concentration change signal.   19. The biological measurement apparatus according to claim 18, wherein the presence / absence or intensity of physiological change is evaluated by an average value or a maximum value of a concentration change signal of oxygenated hemoglobin or a concentration change signal of deoxygenated hemoglobin during the analysis activity period. A biological light measurement device.   15. The biological optical measurement apparatus according to claim 14, wherein the analysis parameter includes physiological change reference waveform data for evaluating the presence or absence of the physiological change or the intensity.   The biological measurement apparatus according to claim 21, wherein when the physiological change to be measured is a salivary gland function, the reference waveform data of the activity for the oxygenated hemoglobin concentration change signal is from 16 seconds to 25 seconds after the start of stimulation. It is a polynomial function having a maximum value in a period, and the reference waveform data of the activity with respect to the deoxygenated hemoglobin concentration change signal is a polynomial function having a minimum value in a period from 28 seconds to 37 seconds after the start of stimulation. A biological light measuring device as a feature.   The biological measurement apparatus according to claim 21, wherein the analysis parameter is stored in advance in a storage unit. A light irradiation means for irradiating the subject with light;
A light receiving means for detecting passing light irradiated from the light irradiating means and propagated through the measurement point in the subject;
An input unit for inputting the type of physiological change to be measured;
Based on the signal detected by the light receiving means, a calculation unit for calculating a concentration change signal of oxygenated hemoglobin and a concentration change signal of deoxygenated hemoglobin at the measurement point;
A measurement unit including a stimulus presentation method and a display unit for displaying a calculation result by the calculation unit;
The living body light measuring device, comprising: displaying different measurement parameters on the display unit according to the type of physiological change input from the input unit.   25. The biological light measurement device according to claim 24, wherein when the physiological change to be measured is a salivary gland function, a stimulus presentation interval of 80 seconds or more is displayed as one of the measurement parameters. .   25. The biological light measurement apparatus according to claim 24, wherein the measurement parameter is stored in advance in a storage unit.

Images