Devices that improve, prevent, or enhance brain function

Abstract

The present invention provides a device and method for controlling brain waves and cell activity by optical stimulation using light of a specific wavelength, such as violet light, either at a constant light level or at a specific flashing frequency, and a device for improving, preventing, or increasing brain function. [Solution] The above-mentioned problems are solved by a device for controlling brain waves and cell activity by irradiating a subject with light of a specific wavelength at a constant light or a specific flashing frequency, the device comprising: a light source that irradiates light of the specific wavelength at a constant light or a specific flashing frequency; and a control unit that controls the emission of light so that the brain waves of the subject exposed to the light induce specific brain waves that are the same as, approximately the same as, or different from those induced by the light irradiation condition. In this case, the light is preferably violet light, and the light irradiation condition is preferably at a constant light or a flashing frequency of more than 0 Hz to 150 Hz.

Description

[Technical Field]

[0001] The present invention relates to a device and method for controlling brain waves and cell activity by optical stimulation using light of a specific wavelength, such as violet light, at a specific flashing frequency, and to a device for improving, preventing, or enhancing brain function. [Background technology]

[0002] The effects of light on the human body have been studied from various perspectives in recent years, and reports have been published based on new findings. For example, it has been reported that exposure to sunlight improves circadian rhythms (Non-Patent Document 1), that light emitted from LED lighting and liquid crystal displays that use LEDs as backlights has a significant effect on the body and mind (Non-Patent Document 2), and that violet light prevents myopia and suppresses the onset of myopia (Patent Document 1). In particular, the present inventors have recently published some interesting reports on the effects of violet light on the eyes. For example, Patent Document 1 and Non-Patent Document 7 propose that light of a specific wavelength is effective in preventing and suppressing myopia, and great expectations are being placed on this in recent years as the number of myopic people continues to increase worldwide.

[0003] Furthermore, research and development of various treatment techniques is also active, particularly those that do not use or reduce the use of drugs and that impose less strain on the body. The present inventors are conducting research and development into the application of light of specific wavelengths, such as violet light, to treatment. As one example, they have proposed a non-invasive corneal and scleral strengthening device and method (unpublished patent) that solves the problems associated with conventional invasive corneal cross-linking, which involves peeling of the corneal epithelium and irradiates UVA at high irradiance, and enables treatment to be performed in everyday life without peeling of the corneal epithelium, eliminating the need to be confined to a medical institution for a certain period of time.

[0004] In addition, Patent Document 2 and Non-Patent Document 4 report that in a study using mice with Alzheimer's disease, when the synchronization of gamma wave oscillations is restored in the brain, amyloid beta protein that had accumulated in the brain is removed. [Prior art documents] [Non-patent literature]

[0005] [Non-Patent Document 1] Megumi Hatori, Kazuo Tsubota, Anti-aging Medicine - Journal of the Japanese Society of Anti-Aging Medicine, Vol.11, No.3, 065(385)-072(392), (2015) [Non-patent document 2] Kazuo Tsubota, "Blue Light: A Threat to the Body Clock," Shueisha, published November 20, 2013 [Non-patent document 3] Hidemasa Torii et al., EBioMedicine, “DOI:http: / / dx.doi.org / 10.1016 / j.ebiom.2016.12.007”. [Non-patent document 4] NATURE,Vol.540,8,DECEMBER 2016,p.231~235. [Patent documents]

[0006] [Patent Document 1] WO2015 / 186723 A1 [Patent Document 2] US2017 / 0304584 A1 Summary of the Invention [Problem to be solved by the invention]

[0007] The present invention is the result of the inventors' discovery that irradiation with violet light at a flickering frequency has an effect on brain waves, and further investigation based on this finding.The purpose of the present invention is to provide an apparatus and method for controlling brain waves and cell activity through optical stimulation using light of a specific wavelength, such as violet light, either at a constant light level or at a specific flickering frequency.

[0008] Another object of the present invention is to provide a device that irradiates violet light or white light at a constant light or a specific flashing frequency to improve or prevent depression, suppress or prevent stress, improve or increase concentration, improve or prevent Alzheimer's disease, and improve or prevent cognitive function; in other words, to provide a device that improves, prevents, or increases brain function. [Means for solving the problem]

[0009] (1) The device for controlling brain waves and cell activity using optical stimulation according to the present invention is a device for controlling brain waves or cell activity by irradiating a subject with light of a specific wavelength at a constant light level or at a specific flashing frequency, and is characterized by having a light source that irradiates light of the specific wavelength at a constant light level or at a specific flashing frequency, and a control unit that controls the emission of light such that the brain waves of the subject exposed to the light induce specific brain waves that are the same as, or approximately the same as, or different from, those induced by the light irradiation condition.

[0010] According to this invention, the brain waves of a subject exposed to light are the same or nearly the same as those of the light irradiation state (constant light or a specific flashing frequency), so by controlling the light irradiation state, it is possible to provide various stimuli to the brain or enhance cellular activity in the body. In particular, when a flashing frequency or the like is irradiated, it is possible to induce specific brain waves that are the same as, nearly the same as, or different from those of the irradiated light irradiation state, so it is possible to control the stimulation state to the brain, which can be applied to various mental and physical improvement effects and therapeutic effects resulting from this.

[0011] In the brain wave and cell activity control device according to the present invention, the light is violet light. According to this invention, violet light with a wavelength outside the visible light range can be irradiated on the subject, so that specific brain waves can be induced that are the same as, approximately the same as, or different from the flashing frequency of the light without causing flicker or glare as with white light. Note that violet light has a wavelength of 360 to 400 nm, which has a lower visual sensitivity than white light and is in a wavelength range that does not or is unlikely to cause discomfort to the subject.

[0012] In the brain wave and cell activity control device according to the present invention, the light irradiation state is constant light or a flashing frequency of more than 0 Hz to 150 Hz. According to this invention, it is possible to induce specific brain waves that are the same as, approximately the same as, or different from such irradiation states.

[0013] In the brain wave and cell activity control device according to the present invention, the light is irradiated at an irradiance of 0.5 to 1000 μW / cm 2 According to this invention, violet light or the like can be irradiated within the above-mentioned irradiance range, so the frequency of brain waves and their generation site can be controlled as desired. It has been confirmed that the above-mentioned characteristic phenomenon occurs even with particularly small amounts of weak light (light with low photosensitivity), and applications to the effects on the brain and cell activity (including gene expression control) are expected.

[0014] In the brain wave and cellular activity control device according to the present invention, the control unit changes and executes the irradiation conditions, such as the irradiation state of the light (including constant light or flashing frequency), irradiance, irradiation time, irradiation start time, irradiation end time, constant light or flashing frequency, by transmitting and receiving information to and from an isolated controller such as a mobile terminal. According to this invention, the various irradiation conditions described above are controlled in isolation, so that the desired effects can be achieved by arbitrarily setting the irradiation conditions suitable for generating the desired brain waves and cellular activity. Furthermore, it is possible to measure and evaluate how irradiation with a specific wavelength light flashing frequency, etc., affects brain waves and cellular activity, and the extent of the impact on the mind and body, and apply the results to practical applications.

[0015] In the electroencephalogram and cell activity control device according to the present invention, the light source is preferably a light source that is installed in front of or near the face, such as light-emitting glasses, a desktop light source, a light source attached to a mobile terminal, etc. According to this invention, specific light can be emitted from a light source that is installed in front of or near the face, such as light-emitting glasses, which are easy to wear and do not cause discomfort in daily life, and therefore is highly practical and can be constantly irradiated in a variety of situations and environments.

[0016] In the electroencephalogram and cellular activity control device according to the present invention, the light source may be a non-installed light source such as a portable light source, or a installed light source such as a room light, a desk lamp, a dedicated device, etc. According to this invention, the device can be configured with various light source forms depending on the usage environment.

[0017] (2) The method for controlling brain wave functions using optical stimulation according to the present invention is a method for controlling brain waves or cell activity by irradiating a subject with light of a specific wavelength at a constant light or a specific flashing frequency, characterized in that light is emitted and controlled so that the brain waves of the subject exposed to the light induce specific brain waves that are the same as, approximately the same as, or different from the constant light or specific flashing frequency.

[0018] (3) The device for improving, preventing, or increasing brain function according to the present invention is a device for improving, preventing, or increasing brain function by irradiating a subject with violet light or white light at a constant light level or at a specific flashing frequency, and is characterized by comprising a light source that emits the violet light or white light, a light emission cycle control unit that sets the violet light or white light to a constant light level or at a specific flashing frequency, and a light emission time control unit that irradiates the violet light or white light for a specific time or for a specific period of time, and is used for one or more purposes selected from the following: improving or preventing depression, suppressing or preventing stress, improving or increasing concentration, improving or preventing Alzheimer's disease, improving sleep, etc.

[0019] (4) The device for improving or preventing brain function according to the present invention is a device for improving or preventing cognitive function by irradiating a subject with constant violet light or white light, and is characterized by comprising a light source that emits the violet light or white light, and an emission time control unit that irradiates the violet light or white light for a specific time or for a specific period of time. [Effects of the Invention]

[0020] According to the present invention, it is possible to provide an apparatus and method for controlling brain waves and cell activity, which irradiates a subject with light of a specific wavelength, such as violet light, either at a constant light level or at a specific flashing frequency, and induces specific brain waves in the subject that are the same as, approximately the same as, or different from the state of the light irradiation. In particular, the apparatus and method are characterized in that the brain waves of the subject exposed to the light can be induced to be the same as, approximately the same as, or different from the state of the light irradiation, and various stimuli can be provided to the mind, body, and brain.

[0021] According to the present invention, a device that irradiates a subject with violet light or white light can improve or prevent depression, suppress or prevent stress, improve or increase concentration, improve or prevent Alzheimer's disease, improve or prevent cognitive function, and even improve sleep. [Brief explanation of the drawings]

[0022] [Figure 1] This is an explanatory diagram of each part of the brain. [Figure 2] (A) shows the result of 10 Hz waves being generated in the occipital lobe by exposure to violet light with a flickering frequency of 10 Hz, and (B) shows the result of 60 Hz waves being generated in the occipital lobe by exposure to violet light with a flickering frequency of 60 Hz. [Figure 3] (A) shows the result of 10 Hz waves being generated in the frontal lobe by exposure to violet light with a flickering frequency of 10 Hz, and (B) shows the result of 60 Hz waves being generated in the frontal lobe by exposure to violet light with a flickering frequency of 60 Hz. [Figure 4] (A) shows the result of no 60 Hz waves being generated in the frontal lobe when exposed to violet light with a flickering frequency of 10 Hz, and (B) shows the result of no 10 Hz waves being generated in the frontal lobe when exposed to violet light with a flickering frequency of 60 Hz. [Figure 5] This is an example of violet light glasses that emit violet light. [Figure 6] 1 is a graph showing the relationship between the spectral irradiance and wavelength of light from a violet fluorescent lamp. [Figure 7] This is the light spectrum of an LED with a peak wavelength of 375 nm. [Figure 8] FIG. 1 is an explanatory diagram of a typical electroencephalogram. [Figure 9] These are the results of an analysis of factors that contribute to a good night's sleep. [Figure 10] This is the result of an analysis of factors that reduce the quality of sleep. [Figure 11] This is the result of an analysis of other factors that contribute to a good night's sleep. [Figure 12] (A) shows the results of evaluation of depression induction using lipopolysaccharide and improvement by 40 Hz frequency stimulation of VL, and (B) shows the results of evaluation of depression induction using CUMS and improvement by constant light or 40 Hz frequency stimulation of VL. [Figure 13] (A) is an explanatory diagram of the measurement location, the left prefrontal cortex Fp1 (International 10-20 system), and (B) is an explanatory diagram showing the measurement time of 30 minutes (1800 seconds) with a 1-minute rest period before and after. [Figure 14] This is the result of a test for the significance of the power spectrum. [Figure 15] The results show that 40Hz frequency stimulation has a stress-suppressing effect. [Figure 16] 10 is a graph showing average stress values for stimuli under each condition. [Figure 17] This is the result of a decrease in phosphorylated tau due to 40 Hz frequency stimulation. [Figure 18] This shows the results of the decrease in phosphorylated tau due to 40 Hz frequency stimulation, similar to those in FIG. [Figure 19] This shows the results of the fear memory evaluation performed using the CFC test. [Figure 20] The results are from the evaluation of spatial memory using the Barnes maze after constant white light stimulation or constant VL stimulation. [Figure 21] This is the result of assessing activity using a running wheel after constant light VL stimulation was given. [Figure 22] 10 is a graph showing changes in gene expression caused by VL constant light stimulation. [Figure 23] 10 is a graph showing changes in expression of other genes caused by VL constant light stimulation. [Figure 24] 10 is a graph showing further changes in gene expression caused by VL constant light stimulation. DETAILED DESCRIPTION OF THE INVENTION

[0023] The present invention will be described with reference to the drawings, in which the device and method for controlling brain waves and cell activity by optical stimulation, and the device for improving, preventing, or increasing brain function are described. The present invention is not limited to the following embodiments and examples, and includes various modifications and applications within the scope of the gist of the present invention.

[0024] [Encephalographic and cellular activity control devices] The device for controlling brain waves and cellular activity by optical stimulation according to the present invention is a device for controlling brain waves or cellular activity by irradiating a subject with light of a specific wavelength at a constant light or a specific flashing frequency, and is characterized by having a light source that irradiates light of the specific wavelength at a constant light or a specific flashing frequency, and a control unit that controls the emission of light such that the brain waves of the subject exposed to the light induce specific brain waves that are the same as, approximately the same as, or different from those induced by the light irradiation state.Furthermore, a method for controlling brain wave function by optical stimulation is a method for controlling brain waves or cellular activity by irradiating a subject with light of a specific wavelength at a constant light or a specific flashing frequency, and is characterized by controlling the emission of light such that the brain waves of the subject exposed to the light induce specific brain waves that are the same as, approximately the same as, or different from those induced by the light irradiation state.

[0025] This brain wave and cell activity control device induces specific brain waves that are the same as, approximately the same as, or different from the light irradiation state in a subject exposed to light, so by controlling the light irradiation state, it is possible to provide various stimuli to the brain or increase cellular activity in the body. In particular, when irradiating with a flashing frequency or the like, it is possible to generate brain waves that are the same as or approximately the same as the light irradiation state or specific brain waves that are different from that irradiation state, so it is possible to control the stimulation state to the brain, which can be applied to various mental and physical improvement effects and therapeutic effects resulting from this. In addition to the irradiation of light with such a flashing frequency or the like, it is also possible to apply sound, vibration, magnetic field, electric field, etc. in combination, thereby producing a combined effect of both.

[0026] Figure 8 shows the commonly understood classification of brain waves. Electrical oscillations (brain waves) occur within the brain via neural circuits, and these brain waves are generally classified into delta waves of approximately 4 Hz or less, theta waves of approximately 4 to 7 Hz, alpha waves of approximately 8 to 13 Hz, beta waves of approximately 14 to 30 Hz, and gamma waves of approximately 30 Hz or higher.

[0027] In the experiments described below, flashing frequencies of 10 Hz and 60 Hz were used as examples, and this range can be said to be the range of alpha waves and gamma waves. Generally, alpha waves are said to be brain waves that occur when the mind and body are relaxed, and gamma waves are said to be brain waves that occur when excited. In the present invention, brain waves of the same or approximately the same frequency as the flashing frequency of the light irradiated with these brain waves can be induced in the subject. It is also possible to induce different specific brain waves.

[0028] The present invention has a notable feature in that it can induce brain waves of the same or approximately the same frequency as the flashing frequency of the irradiated light, or brain waves of a specific different frequency, and by controlling the generation of such brain waves through the light irradiation conditions, it is possible to impart to the subject the above-mentioned psychosomatic effects based on brain waves, such as emotion, motivation, memory, concentration, relaxation, elation, awakening, sleep, drowsiness, sleep induction, dreaming, etc. At present, human experiments have produced results in various areas, such as improved sleep, relaxation, and dreaming (dreams are effective for memory formation just before non-REM sleep). Furthermore, it is highly expected that the compound will have an effect on cell activation based on brain waves and on diseases, such as fluctuations in neurotransmitters in the brain, fluctuations in endocrine secretions, effects on proteins, Alzheimer's disease, brain dysfunction, age-related macular degeneration of the retina, addiction, depression, dissociative disorders, obsessive-compulsive disorders, sleep disorders, eating disorders, bipolar disorder (manic depression), adjustment disorders, dyspraxia, dementia, personality disorders, developmental disorders, panic disorders, PTSD, gender identity disorder, epilepsy, etc., and will have an effect on cell activation, and is expected to have an effect on various mind-body or physical actions (including therapeutic effects).

[0029] [Encephalographic stimulation of brain waves] Figures 2 to 4 show the results of measuring brain waves when exposed to flashing light. As shown in Figures 2(A) and 3(A), irradiating violet light at a flashing frequency of 10 Hz resulted in the generation of 10 Hz waves in the occipital and frontal lobes. Furthermore, as shown in Figures 2(B) and 3(B), irradiating violet light at a flashing frequency of 60 Hz resulted in the generation of 60 Hz waves in the occipital and frontal lobes. On the other hand, as shown in Figure 4, when violet light was irradiated at a flashing frequency of 10 Hz, no 60 Hz waves were generated in the frontal lobe, and when violet light was irradiated at a flashing frequency of 60 Hz, no 10 Hz waves were generated in the frontal lobe. These results demonstrate the extremely surprising phenomenon of brain waves being generated at frequencies that are the same as or approximately the same as the flashing frequency of the irradiated light. Furthermore, in this experiment, a weak light (low irradiance) violet light was used, which is not dazzling and is less distracting than white light, so there was no glare, distraction, or flickering that often occurs with visible light such as white light.In particular, by increasing the flashing frequency to a level where the flashing is not noticeable, the device was found to be practical enough to withstand use in everyday life.

[0030] The light source, irradiation conditions, electroencephalogram measurement, etc. used in the measurements of FIGS. 2 to 4 will be explained below.

[0031] The light source has a maximum output of 310 μW / cm in the experimental examples shown in Figures 2 to 4. 2 We used glasses (see Figure 5) with a 375 nm LED attached to a frame with an irradiance of 1000 Hz. This LED exhibits the spectral wavelength shown in Figure 7 and emits violet light defined as 360 to 400 nm. This light source has a control unit (electronic circuit unit) that can adjust the output within a range below the maximum output mentioned above. It also has a function that can arbitrarily change the flashing frequency, and can emit violet light in the range of 0 Hz ("normal light" - DC light) to 150 Hz. The irradiation conditions in this experiment were flashing frequencies of 10 Hz and 60 Hz. The light source used had a flashing frequency duty cycle of 50%.

[0032] The test method was an open-closed-eyes test while awake and at rest with eyes closed (Awakerecord) in the following order: (1) Electromyograms were taken with the eyes closed and when the subject blinked while at rest without wearing light-emitting glasses (hereafter simply referred to as "glasses"), and which signals corresponded to brain waves. (2) After that, brain waves were measured for 5 minutes without wearing glasses and in a normal state with natural blinking. (3) After that, brain waves were measured while wearing glasses and shining a violet light with a flashing frequency of 10 Hz on the eyes for 5 minutes. (4) After that, brain waves were measured while shining a violet light with a flashing frequency changed to 60 Hz on the eyes for 5 minutes. The brain waves were measured using an electroencephalograph (Nihon Kohden Corporation, EEG-1200 series model).

[0033] The results of Figures 2 to 4 show that when the frequency of the violet light was changed from 10 Hz to 60 Hz, the brain waves also followed the change, changing from 10 Hz to 60 Hz. Furthermore, it was found that the brain waves' adaptation to the light frequency occurred not only in the occipital lobe but also in the frontal lobe, demonstrating that the brain waves generated by exposure to violet light are frequency-dependent.

[0034] 9 to 11 show data from application software obtained when the inventor wore glasses with a light source (FIG. 5) as needed during daily life. FIGS. 9 and 11 show the contribution to the quality of sleep when irradiated with violet light flashing at frequencies of 10 Hz, 40 Hz, and 60 Hz, while FIG. 10 shows the percentage reduction in the quality of sleep. Irradiation with a violet light flashing frequency generates brain waves that are the same as or approximately the same as the flashing frequency, and it was confirmed that the brain waves thus generated have a certain effect on the quality of sleep.

[0035] In this experiment, the light used was violet light with a wavelength of 360-400 nm, and the results were obtained at frequencies of 10 Hz, 40 Hz, and 60 Hz. However, the dependence of brain waves on the flashing frequency of the irradiated light suggests that similar phenomena will occur with other frequencies (e.g., 9 Hz, 30 Hz, 60 Hz, or higher). Furthermore, although the wavelength of the light used here was violet light, it is expected that light in other wavelength ranges will also generate brain waves that are the same or nearly the same as the flashing frequency of the irradiated light. Furthermore, brain waves are known to affect mental and physical functions such as emotion, motivation, memory, concentration, relaxation, elation, and alertness, and this device can be designed to induce such mental and physical effects. Furthermore, it is expected that brain waves can be used to stimulate cellular activity and treat diseases.

[0036] (light source) The wavelength of light emitted by the light source is not particularly limited, but in the above experiments, violet light defined as 360 to 400 nm was used. Similar effects can be expected with other wavelengths besides violet light, and they can also be used in combination with violet light. Furthermore, as shown in the results described below, white light also exhibits a certain degree of effectiveness, so white light may be the light emitted from the light source or may be part of the light.

[0037] A light source capable of oscillating at a frequency between 0 (constant light, DC light) and 150 Hz is preferably used. The frequency can be adjusted in 0.5 Hz or 1 Hz increments by setting the control unit, making it possible to generate light with any desired flashing frequency. Increasing the flashing frequency has the advantage that the flashing becomes less noticeable, although this will vary from person to person. The flashing frequency is not limited to the 10 Hz or 60 Hz used in the experimental example.

[0038] The irradiance from the light source may be variable or constant. In the above experiment, the maximum output was 310 μW / cm 2 However, this is not limited to this. For example, 1 μW / cm 2 (0.01W / m 2 )~1000μW / cm 2 (10W / m2 ) and, for example, 0.5 μW / cm 2 (0.005W / m 2 )~500μW / cm 2 (5W / m 2 ) and those in the range of 0.5 to 1000 μW / cm 2 The light source can be configured to have any desired intensity, such as within the range of 1000 to 15000 kJ / s. Since brain waves with the same or approximately the same frequency as the flashing frequency can be generated even at low irradiance, a predetermined brain wave can be generated by irradiating the flashing frequency with the eyes open or closed. Furthermore, a light source with such irradiance can be easily applied to eyeglasses and other portable irradiation devices, so that it can be worn in daily life. It has been confirmed that the above-mentioned characteristic phenomenon occurs even with particularly weak light (light with low photosensitivity), and applications to the effects on the brain and cell activity (this term also includes gene expression control) are expected.

[0039] The light may be specified by the relative luminous efficiency. Since the features of the present invention can be realized even with a low relative luminous efficiency, it is possible to irradiate a violet light that generates electroencephalographic stimulation under a low relative luminous efficiency, and to stimulate the desired area without burdening the subject.

[0040] The irradiation time of light is preferably set arbitrarily depending on the purpose, and may be short or long. The light may be applied intermittently (at regular or irregular intervals) or continuously.

[0041] The light source is preferably a pair of light-emitting glasses. Such glasses are easy to wear and comfortable to wear on a daily basis, and are equipped with a light source that emits a flashing frequency, making them highly practical and allowing them to be worn constantly in a variety of situations and environments. The light source may be a light source installed in front of or near the face, such as a desktop light source or a light source attached to a mobile terminal, or a non-installed light source, such as a portable light source, or a installed light source, such as a room light, a desktop lamp, or a dedicated device, and various light source forms can be used depending on the usage environment.

[0042] (Control unit) The control unit is a part that controls the illumination state of the light from the light source (constant light or flashing frequency). The control unit may be equipped with a power source (not shown) for supplying power to the light source, which may be a battery or may be a power source that is connected to a battery installed in another location via a cable. In addition, if the light source is not moved in one place, it may be configured to be connected to a household power source or the like.

[0043] The control unit preferably changes the irradiation conditions, such as the light flashing frequency, irradiance, irradiation time, irradiation start time, irradiation end time, and flashing frequency, by transmitting and receiving information to and from an isolated controller such as a mobile terminal. Since such a control unit controls the various irradiation conditions described above in isolation, it is possible to arbitrarily set irradiation conditions suitable for generating desired brain waves and cellular activity, thereby achieving the desired effect. Furthermore, it is possible to measure and evaluate how irradiation with a specific wavelength light flashing frequency affects brain waves and cellular activity, and the extent of the impact on the mind and body, and to apply the results to practical applications.

[0044] Furthermore, the control unit may have a light source controller or timer function. Examples of the controller include functions to vary the frequency and irradiance, and to set the irradiation time. Examples of the timer function include a function to set the irradiance time of the light. Such a controller or timer function may be provided integrally with the device or may be a separate component.

[0045] As described above, the device for controlling brain waves and cell activity by optical stimulation according to the present invention can irradiate a subject with light of a specific wavelength, such as violet light, either at a constant light level or at a specific flashing frequency, and can induce brain waves in the subject that are the same as or approximately the same as the light irradiation state, or can induce specific brain waves that are different from the light irradiation state. In particular, the brain waves of a subject exposed to light can be induced to be the same as, approximately the same as, or different from the flashing frequency of the light, thereby providing various stimuli to the mind, body, and brain.

[0046] [Brain function improvement or augmentation device] In the present invention, further research was conducted into the effects of light stimulation using violet light or white light. As a result, it was found that light stimulation using violet light or white light can be expected to improve or prevent depression, suppress or prevent stress, improve or increase concentration, improve or prevent Alzheimer's disease, and improve or prevent cognitive function. This was the first time that such effects were observed with light stimulation using violet light or white light, and led to the development of the device for improving, preventing, or enhancing brain function according to the present invention.

[0047] The device for improving, preventing, or increasing brain function according to the present invention is a device that improves, prevents, or increases brain function by irradiating a subject with violet light or white light at a constant light level or at a specific flashing frequency, and is characterized by comprising a light source that emits the violet light or white light, an emission cycle control unit that sets the violet light or white light to a constant light level or at a specific flashing frequency, and an emission time control unit that irradiates the violet light or white light for a specific time or for a specific period of time, and is used for any one or more purposes selected from the following: improvement or prevention of depression, suppression or prevention of stress, improvement or increase of concentration, improvement or prevention of Alzheimer's disease, and improvement of sleep.

[0048] Furthermore, the device for improving or preventing brain function according to the present invention is a device for improving or preventing cognitive function by irradiating a subject with constant violet light or white light, and is characterized by comprising a light source that emits the violet light or white light, and an emission time control unit that irradiates the violet light or white light for a specific time or for a specific period of time.

[0049] These improvements or enhancements of brain function will be explained in order. Violet light will be abbreviated as "VL" below.

[0050] (Improvement of depression) Mice were exposed to constant white light (WL continuous), constant variable light (VL continuous), or 40 Hz VL stimulation (VL 40 Hz). C57BL / 6 mice aged 8–13 weeks were used.

[0051] Depression can be assessed using the tail suspension test (TST, https: / / www.jove.com / video / 3769 / ?language=Japanese), which involves suspending a mouse by its tail and measuring its struggles, and the forced swim test (FST, https: / / www.jove.com / video / 3638 / the-mouse-forced-swim-test), which involves forcing the mouse to swim in a small pool and measuring its struggles. The TST was used for this study. The degree of "giving up" is used as an index of depression, and non-patent literature on its assessment includes "Journal of Visualized Experiments January 2012, 59, e3638, Page 1 of 5," "Journal of Visualized Experiments January 2012, 59, e3769, Page 1 of 5," and "Neuron 53, 337-351, February 1, 2007 a2007 Elsevier Inc. 337."

[0052] Figure 12(A) shows the results of lipopolysaccharide (LPS)-induced depression and its improvement by 40 Hz stimulation of the VL. Mice were administered LPS to induce acute inflammatory depression. 40 Hz stimulation of the VL was performed for a total of 8 days, before and on the day of LPS administration, and depression was assessed by the tail suspension test (TST). The reference used for the LPS-induced depression experiment is https: / / www.nature.com / articles / s41598-019-42286-8. As shown in Figure 12(A), 40 Hz stimulation of the VL reduced depressive symptoms. The immobility time in the TST was measured using ANY-maze (Video Tracking System, Muromachi Kikai Co., Ltd.). Statistical significance was assessed between the control group, LPS group, and LPS + 40 Hz stimulation group using GraphPad Prism 8.0 software, and the results are shown in Figure 12. Note that "*" indicates p<0.05 and "**" indicates p<0.01.

[0053] Figure 12(B) shows the results of inducing depression using chronic unpredictable mild stress (CUMS) and evaluating the improvement of depression with constant light or 40 Hz VL stimulation. The reference used for the CUMS-induced depression experiment is https: / / www.sciencedirect.com / science / article / pii / S0149763418304378?via%3Dihub. Mice were exposed to various relatively mild stresses on alternating days for a long period (7 weeks) to induce a chronic psychologically depressed state. During this period, VL constant light stimulation or VL 40 Hz frequency stimulation was administered, and depression was evaluated using the TST. As shown in Figure 12(B), VL constant light stimulation or VL 40 Hz frequency stimulation improved depressive symptoms.

[0054] (Reducing stress, increasing concentration) We analyzed the effects of VL on stress reduction and increased concentration. For stress data, electroencephalogram (EEG) measurements and evaluation methods were performed using the methods described in the non-patent literature in Sensors 2018, 18(12), 4477 (https: / / doi.org / 10.3390 / s18124477, https: / / www.mdpi.com / 1424-8220 / 18 / 12 / 4477 / htm).

[0055] The experiment used VL and white light, and photic stimulation was performed with flashing and constant illumination (referred to as "constant light"). The measured EEG was analyzed by preprocessing, filtering, and power spectrum calculation using FFT (fast Fourier transform). A significance test was performed based on the results. A total of 162 subjects were included. Measurements were performed on the left prefrontal cortex Fp1 (International 10-20 system) shown in Figure 13(A). The measurement period was 30 minutes (1800 seconds), with a 1-minute rest period before and after, as shown in Figure 13(B). The photic stimuli used during measurement included constant white light stimulation, white light frequency stimulation, VL constant light stimulation, and VL frequency stimulation. VL stimulation was performed using VL glasses (see Figure 5), and white light stimulation was performed at a frequency of 40 Hz. A simple electroencephalograph (sampling frequency: 512 Hz, MindWave mobile BMD version, Neurosky Inc.) was used as the measurement device.

[0056] The analysis was performed using the following procedure. EEG was measured using 81 subjects receiving VL stimulation and 81 subjects receiving white light stimulation under eight conditions (seven conditions for each type of stimulation and one condition of lights out). The duration of the stimulation was 30 minutes (1800 seconds), as shown in Figure 13(B). The obtained measurement data was subjected to noise removal (filtering with 1 to 70 Hz effective), power spectrum calculation (Hilbert transform, spline interpolation), and one-sided power spectrum calculation. This procedure was performed as the standard procedure.

[0057] A significant difference test was performed to analyze the frequency components of EEG affected by light stimulation. Specifically, a two-tailed, two-sample t-test (significance level: 5%) was performed for healthy male and female subjects. A significance test was performed to compare the 1 Hz power spectrum (average of subjects) under seven conditions of frequency stimulation and constant light stimulation with constant light off. Power spectra from 2 to 45 Hz were also compared. Figure 14 shows the results of the significance test for power spectra (light stimulation vs. lights off). As shown in Figure 14, when frequencies were stimulated at 10 Hz, 12 Hz, 13 Hz, 15 Hz, 40 Hz, and 60 Hz, the power spectra at 16 Hz, 38 Hz, and 44 Hz were significantly larger than those at 40 Hz (significance level: 5%). On the other hand, no significant differences were observed for frequencies at 10 Hz, 12 Hz, 13 Hz, 15 Hz, and 60 Hz. Furthermore, the power spectrum at 3 Hz was significantly smaller under constant light.

[0058] Next, we investigated the effect of 40 Hz frequency stimulation on stress suppression. Healthy male and female subjects were given 40 Hz white light stimulation and 40 Hz VL stimulation before, during, and after the task. Noise reduction and power spectrum analysis were performed on EEG data measured using a simple electroencephalograph, and stress values (%) were calculated. The analysis method was based on https: / / www.mdpi.com / 1424-8220 / 18 / 12 / 4477. The results are shown in Figure 13. Figure 15(A) shows stress values before and after no stimulation, Figure 15(B) shows stress values before and after VL 40 Hz frequency stimulation, and Figure 15(C) shows stress values before and after white light 40 Hz frequency stimulation. It was found that 40 Hz frequency stimulation reduced stress compared to before stimulation and after the task without stimulation.

[0059] Figure 16 is a graph showing the average stress values for stimulation under each condition ("*" indicates p<0.05). Healthy male and female subjects were given VL frequency stimulation of 10 Hz, 12 Hz, 13 Hz, 15 Hz, 40 Hz, and 60 Hz, as well as constant light stimulation. Noise removal and power spectrum analysis were performed on the electroencephalogram measured using a simple electroencephalograph, and the stress value (%) was examined. The results showed that stress was reduced by 10 Hz and 40 Hz frequency stimulation.

[0060] The subjects were asked to rate on a 5-point scale whether they could read the paper during the light stimulation experiment well or not, to investigate the possibility of improving intellectual productivity. The results for VL frequency stimulation were "I could read very well: 5.9%," "I could read well: 41.2%," "It was average: 47.1%," "I couldn't read very well: 5.9%," and "I couldn't read at all: 0%." On the other hand, for white light frequency stimulation, the results were "I could read very well: 0%," "I could read well: 5.9%," "It was average: 70.6%," "I couldn't read very well: 23.5%," and "I couldn't read at all: 0%."

[0061] (Improvement of Alzheimer's disease) The ameliorative effect on Alzheimer's disease was evaluated by administering constant white light stimulation (WL continuous), 40 Hz white light stimulation (WL 40 Hz), constant VL stimulation (VL continuous), and 40 Hz VL stimulation (VL 40 Hz) to mice.

[0062] Tau (tau) is known to be the causative gene for Alzheimer's disease in humans. Mutations in this gene are known to cause Alzheimer's disease, and in 1999, the tau gene mutation S301P was identified as a mutation in familial genetic diseases such as Parkinson's disease and frontotemporal dementia. In this experiment, mice carrying human S301P tau were used for evaluation. Tau phosphorylation is actually a diagnostic for Alzheimer's disease, and is detected using an antibody called AT8 (pSer202 / Thr205). The first paper evaluating S301P mice for Alzheimer's disease is https: / / www.ncbi.nlm.nih.gov / pubmed / 17270732, which was used in this experiment.

[0063] Figures 17 and 18 show the results of the reduction of phosphorylated tau by 40 Hz stimulation. In Figures 17 and 18, (A) shows the images of DAPI, p-tau, and GFAP, and (B) shows the graph of GFAP area percentage obtained by analyzing the images. Three-month-old S301P mutant mice were subjected to constant white light stimulation, 40 Hz white light stimulation, and 40 Hz VL stimulation for 4 weeks. Phosphorylated tau (Ser202, Thr205) was detected using the AT8 antibody. 40 Hz VL stimulation reduced the accumulation of phosphorylated tau in the hippocampus (left graph in Figure 17(B)), reduced the accumulation of phosphorylated tau in the CA3 region (graph in Figure 18(B)), and increased GFAP in astrocytes (right graph in Figure 17(B)).

[0064] (Improvement of cognitive function) The effect of improving cognitive function in aged mice was evaluated by administering constant white light stimulation (WL continuous), 40 Hz white light stimulation (WL 40 Hz), constant VL stimulation (VL continuous), and 40 Hz VL stimulation (VL 40 Hz).

[0065] In cognitive memory experiments, two types of memory are assessed: fear memory and spatial memory. Fear memory is assessed by the time the animal freezes and remains motionless after receiving an electric shock. The animal freezes immediately after receiving the electric shock, but the next day, if the animal is placed in the shock machine and does not remember what happened the previous day, the freezing time decreases (Reference: https: / / www.ncbi.nlm.nih.gov / books / NBK5223 / ). Meanwhile, spatial memory is assessed by placing a mouse on a white disk and shining a strong light on it. Nocturnal mice attempt to escape to a dark area. The disk contains 20 holes, 19 of which are blocked, but only one hole is open for escape. The mouse undergoes six days of training to memorize the location of that hole. The extent to which the mouse can remember the location of that hole is assessed one day and one week later (Reference: https: / / www.nature.com / protocolexchange / protocols / 349Reiserer).

[0066] Fear memory was evaluated using the contextual fear conditional test (CFC). After 7 weeks of constant white light stimulation or constant VL stimulation in 64-week-old mice, fear memory was evaluated using CFC. As shown in Figure 19, constant VL stimulation improved the freezing score in the CFC.

[0067] A Barnes maze test was performed. After 11 weeks of constant white light stimulation or constant VL stimulation in 64-week-old mice, spatial memory was evaluated using the Barnes maze. The mice were trained to memorize the maze for 6 days, and then a probe (memory test) was administered 7 days later to measure long-term memory. As shown in Figure 20, the scores of the aged mice were improved by constant VL stimulation. Two-way ANOVA showed a P value of <0.05.

[0068] Activity was assessed. After 12 weeks of constant light VL stimulation in 75-week-old mice, activity was assessed using a running wheel. As shown in Figure 21, the activity scores of the aged mice improved with white light 40 Hz stimulation, constant light VL stimulation, and VL 40 Hz stimulation.

[0069] The changes in gene expression caused by constant VL stimulation were investigated and are shown in Figures 22 to 24. 67-week-old aged mice were given constant VL stimulation for 13 weeks. The gene expression changes in these mice were compared with those in 15-week-old young mice and 67-week-old aged mice under constant white light conditions. "*" indicates p<0.05, "**" indicates p<0.01, and "***" indicates p<0.001.

[0070] As shown in Figures 22 to 24, constant VL stimulation increased opn5 gene expression (see Figure 22(A)), apoptosis-related gene Bax (see Figure 22(B)), Bcl2 gene expression (see Figure 22(C)), apoptosis-related gene Caspase 3 (see Figure 23(A)), Caspase 9 gene expression (see Figure 23(B)), oxidative stress and mitochondria-related genes Glutathione peroxidase and PGC1α (see Figures 24(A)(B)), and cell cycle and cellular senescence-related p21 gene expression (see Figure 24(C)).

[0071] Regarding the mechanism by which VL stimulation activates brain function and cells, it is currently believed to be mediated by a VL-specific photoreceptor (neuropsin) called OPN5. A reference document indicating that OPN5 is a VL neuropsin present in the retina is https: / / journals.plos.org / plosone / article?id=10.1371 / journal.pone.0026388. However, the light stimulation described above in the present invention does not necessarily pass through the eye, but may penetrate the skull and affect the brain directly (see: https: / / www.cell.com / current-biology / fulltext / S0960-9822(14)00603-4). Based on the results shown in Figure 22, it is believed that VL irradiation increases OPN5 gene expression in the present invention.

[0072] As shown by the above results, the brain function improving or increasing device according to the present invention can improve or prevent depression, suppress or prevent stress, improve or increase concentration, improve or prevent Alzheimer's disease, improve or prevent cognitive function, and even improve sleep by irradiating a subject with violet light or white light.

Claims

1. A device for improving or preventing brain function by irradiating a subject with constant violet light of 360 to 400 nm, which is a wavelength outside the visible light range, a light source that emits the violet light; a light emission cycle control unit that keeps the violet light on at all times; and a light emission time control unit that irradiates the violet light for a specific time or for a specific period of time; The violet light is applied at an irradiance of 0.5 to 1000 μW / cm ２ A device for improving or preventing brain function, characterized in that it is a device that irradiates within a range of 100 nm to 120 nm and is used for one or more of the purposes of improving or preventing Alzheimer's disease and improving or preventing cognitive function.

2. 2. The device for improving or preventing brain function as described in claim 1, wherein the device changes the illumination state, irradiance, illumination time, illumination start time, illumination end time, or constant illumination conditions of the violet light by transmitting and receiving data to and from an isolated controller such as a mobile terminal.

3. 3. The device for improving or preventing brain function according to claim 1 or 2, wherein the light source is a light source installed in front of or near the face, such as light-emitting glasses, a desktop light source, or a light source attached to a mobile terminal, a non-installed light source such as a portable light source, or a installed light source such as indoor lighting, a desktop lamp, or a dedicated device.

4. 3. The device for improving or preventing brain function according to claim 1 or 2, wherein light of another wavelength, sound, vibration, magnetic field, or electric field is also applied in addition to the irradiation of the violet light.

5. 3. The device for improving or preventing brain function according to claim 1, wherein the violet light is irradiated for at least 30 minutes.

6. An apparatus for improving or preventing brain function as described in claim 1 or 2, wherein the irradiation of the subject with violet light is irradiation of the subject's eyes.

7. A device that improves, prevents, or enhances brain function by irradiating a subject with constant violet light of 360 to 400 nm, which is a wavelength outside the visible light range. a light source that emits the violet light; a light emission cycle control unit that keeps the violet light on at all times; and a light emission time control unit that irradiates the violet light for a specific time or for a specific period of time; The violet light is applied at an irradiance of 0.5 to 1000 μW / cm ２ and is used for one or more of the following purposes: improvement or prevention of depression, suppression or prevention of stress, improvement or increase of concentration, improvement or prevention of Alzheimer's disease, improvement of sleep, and improvement or prevention of cognitive function. A device for improving, preventing, or increasing brain function, characterized in that the light source is light-emitting glasses.

8. An apparatus for improving, preventing or increasing brain function as described in claim 7, which changes the irradiation state, irradiance, irradiation time, irradiation start time, irradiation end time, or constant light irradiation conditions of the violet light by transmitting and receiving data to and from an isolated controller such as a mobile terminal.

9. A device for improving, preventing, or increasing brain function as described in claim 7 or 8, which applies light, sound, vibration, magnetic field, or electric field of another wavelength in addition to the irradiation of violet light.

10. An apparatus for improving, preventing or increasing brain function as described in claim 7 or 8, wherein the irradiation time of the violet light is at least 30 minutes.

11. An apparatus for improving, preventing or increasing brain function as described in claim 7 or 8, wherein the irradiation of the subject with violet light is irradiation of the subject's eyes.

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