Treatment of central nervous system disorders

Abstract

Devices and methods for treating central nervous system disorders by administering light to a user are disclosed. In some embodiments, the device is placed remote from the user, while in other embodiments, the device is attached to the user. In some embodiments, the light is applied through the user's skin, while in other embodiments, the light is applied through an implanted or transdermal device. Representative central nervous system disorders include cognitive, motor, and behavioral disorders. In cases where these disorders include an inflammatory component, light is administered at a wavelength that reduces inflammation in the brain. In cases where these disorders are caused by poor vascularization, light is administered at a wavelength that improves vascularization in the brain. The method also includes repairing damage to the blood-brain barrier and can be used to more effectively administer drugs to the brain, such as anti-cancer drugs.

Description

Technical Field

[0001] Disclosed are treatments for central nervous system disorders and devices for administering such treatments. The treatments involve administering electromagnetic radiation at specific wavelengths to a user, and the devices are capable of administering these treatments. In various embodiments, the treatments can increase vascularization in the brain, decrease inflammation in the brain, and / or increase drug passage through the blood-brain barrier, thereby treating a variety of central nervous system disorders. Background Art

[0002] Inflammation and adverse angiogenesis each play a role in central nervous system disorders.

[0003] CNS shows inflammatory characteristics. In response to damage, infection or disease, resident CNS cells produce inflammatory mediators, including proinflammatory cytokines, prostaglandins, free radicals and complement, which then induce chemokines and adhesion molecules, recruit immune cells and activate neuroglial cells. Inflammation and inflammatory mediators can cause acute, chronic and mental CNS disorders (see, for example, Lucas, Sian-Marie et al. "The role of inflammation in CNS injury and disease." British journal of pharmacology vol.147Suppl 1, (2006): S232-40.doi:10.1038 / sj.bjp.0706400).

[0004] Some key features of CNS inflammation include glial activation, edema, MHC expression, systemic acute phase response with systemic inflammation and acute phase protein synthesis, complement activation - such as anaphylatoxins and membrane attack complex, synthesis of inflammatory mediators - such as cytokines, free radicals and prostaglandins, expression of adhesion molecules, and invasion of immune cells. Neurons, astrocytes, microglia and oligodendrocytes can produce inflammatory mediators, and cytokine receptors are constitutively expressed throughout the CNS.

[0005] Interleukin (IL) -1 is an inflammatory mediator present in patients with stroke or traumatic brain injury. Acute administration of the naturally occurring antagonist IL-1ra can inhibit inflammation and treat stroke and traumatic brain injury (Tehranian et al., J. Neurotrauma, 2002; 19: 939-951). However, long-term administration may be undesirable because interleukin (IL) -1 includes growth factors, reduces glutamate release, enhances GABA action, regulates neuronal responses to NMDA and glycine, and increases activation of inducible nitric oxide synthase (iNOS), which can help healing, especially in the case of increased activation of iNOS, which can increase angiogenesis in the CNS. Tumor necrosis factor-α (TNFα) is one of the central mediators of tissue inflammation and is also associated with the pathogenesis of many neurological disorders.

[0006] The mechanisms controlling the expression of different cytokines are often related; TNFα stimulates the expression of IL-1 and IL-6, and IL-1 can induce IL-6 and TNFα. Thus, after brain injury, the initial upregulation of cytokines leads to the infiltration of other inflammatory mediators into the site of injury, initiating secondary cytokine signaling.

[0007] CNS inflammation has been implicated in acute brain injury, stroke, epilepsy, multiple sclerosis (MS), motor neuron disease, movement disorders, Alzheimer's disease, and psychiatric disorders such as depression, anxiety, and schizophrenia.

[0008] Anti-inflammatory agents can reduce the likelihood of developing AD, or slow its progression. Many inflammatory mediators are upregulated in MS and are associated with demyelinating lesions (Raivich et al., Brain Res. Brain Res. Rev. 2004; 46: 261–281). Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra, as well as motor symptoms of tremor, muscle rigidity, and bradykines. The role of inflammation has been strongly implicated (Gao et al., Trends Pharmacol Sci. 2003 Aug; 24 (8): 395-401). Inflammation is also thought to contribute to other chronic CNS disorders, such as amyotrophic lateral sclerosis (ALS) (Yoshihara et al., J Neurochem. 2002 Jan; 80 (1): 158-67), and Creutzfeldt-Jakob disease (CJD) (Van et al., 2002). Serum levels of many cytokines, including IL-1β and IL-6, are increased in patients with schizophrenia and depression. Epilepsy is associated with elevated levels of IL-1 and TNFα.

[0009] Inadequate blood flow damages and eventually kills cells, and the brain is particularly vulnerable. An estimated 15% to 20% of dementia cases in older adults are caused by vascular dementia. Cognitive decline can occur suddenly after a stroke, which blocks a major blood vessel in the brain. Microvascular ischemic encephalopathy, also known as small vessel disease, is a narrowing of blood vessels that results in a significant reduction in blood supply to brain tissue. It is associated with memory loss and is caused by poor blood vessel formation.

[0010] Vascular disease can lead to depression, cognitive impairment and poor antidepressant response in the elderly, which supports the view that angiogenesis plays a key role in depressive symptoms. At least some antidepressants selectively increase human hippocampal neural progenitor cells (NPCs) and angiogenesis in the anterior and middle dentate gyri (DG). (Boldrini, Maura et al. "Hippocampalangiogenesis and progenitor cell proliferation are increased with antidepressant use in major depression." Biological psychiatry vol. 72, 7 (2012): 562-71. doi: 10.1016 / j.biopsych.2012.04.024).

[0011] In vascular Parkinson's disease, small strokes in the brain areas that control movement can cause Parkinson's-like symptoms (Miguel-Puga, Adán et al. "Therapeutic Interventions for Vascular Parkinsonism: A Systematic Review and Meta-analysis." Frontiers in neurology vol.8481.22Sep.2017, doi:10.3389 / fneur.2017.00481). This suggests a causal relationship between poor blood vessel formation in the brain and certain movement disorders.

[0012] Cerebrovascular disease includes a variety of medical conditions that affect the cerebral blood vessels and cerebral circulation and are associated with movement and cognitive impairments, including stroke, migraine, seizures, epilepsy, and cognitive decline.

[0013] Thus, angiogenesis and inflammation play a role in many CNS disorders.

[0014] Damage to the blood-brain barrier (BBB) ​​can also lead to a variety of CNS disorders. Disorders associated with a compromised blood-brain barrier include Alzheimer's disease (van de Haar HJ, et al., "Blood-Brain Barrier Leakage in Patients with Early Alzheimer Disease". Radiology. 282(2): 615 (February 2017)), anxiety and depression (Gal Z, Huse RJ, Gonda X, Kumar S, Juhasz G, Bagdy G, Petschner P (March 2019). "Anxiety and depression-the role of blood-brain barrier integrity" . Neuropsychopharmacologia Hungarica. 21(1): 19–25), brain abscesses (caused by inflammation and accumulation of lymphocytes and infectious agents from local or remote infections), De Vivo disease (also known as GLUT1 deficiency syndrome, resulting from insufficient transport of the sugar glucose across the blood-brain barrier, usually due to a genetic defect in glucose transporter type 1 (GLUT1), HIV encephalitis (Ivey NS, MacLean AG, Lackner AA (April 2009). "Acquired immunodeficiency syndrome and the blood-brain barrier". Journal of Neurovirology. 15(2): 111–22), meningitis (related to inflammation of the membranes surrounding the brain and spinal cord, i.e., the meninges), multiple sclerosis (Waubant E (2006). "Biomarkers indicative of blood-brain barrier disruption in multiple sclerosis". Disease Markers. 22(4): 235–44), and neuromyelitis optica, also known as Devic's disease, which is similar to multiple sclerosis.

[0015] While pharmaceutical agents are available to treat many of these disorders, it would be advantageous to provide adjunctive therapies to minimize inflammation in the brain, increase vascularization, and / or repair the blood-brain barrier. The present invention provides such adjunctive therapies. Summary of the invention

[0016] A variety of specific treatments for central nervous system disorders and devices that can deliver these treatments are disclosed, which treatments involve the administration of electromagnetic radiation at specific wavelengths.

[0017] In some embodiments, the treatment is designed to simplify the delivery of electromagnetic radiation to the user and / or can enhance user compliance with such treatment, and in some embodiments, requires little or no effort from the user to receive the treatment.

[0018] Central nervous system disorders that can be treated using the treatments and devices described herein include cognitive disorders, movement disorders, and behavioral disorders. In some embodiments, the treatment reduces inflammation in the brain and is therefore useful for treating central nervous system disorders associated with inflammation. In other embodiments, the treatment increases angiogenesis in the brain and is therefore useful for treating central nervous system disorders associated with reduced angiogenesis in the brain. In other embodiments, the treatment repairs defects in the blood-brain barrier and / or increases the flow of drugs and other agents through the blood-brain barrier and is therefore useful for treating disorders associated with a defective blood-brain barrier and / or increases the ability of drugs to cross the blood-brain barrier and treat brain disorders (such as brain cancer).

[0019] Combinations of these approaches can be used, for example by administering light at more than one wavelength, where the combination of wavelengths is effective for one or more of: increasing vascularization, reducing inflammation, and increasing passage of agents across the blood-brain barrier. When administered at antimicrobial wavelengths, the light can also be used to inhibit microbial infection in the brain.

[0020] Light can be delivered to various parts of the body. When applied to the head, light can be applied at an extracranial location, such as through the external auditory canal, or transcranially through one or more of the following skull bones: temporal bone, squamosal temporal bone, mastoid temporal bone, petrous temporal bone, tympanic temporal bone, zygomatic bone, sphenoid bone, frontal bone, parietal bone.

[0021] The treatments and devices for administering them may use one or more light sources, such as LEDs, OLEDs, laser light sources, and combinations thereof.

[0022] Devices for administering these treatments typically include a housing, one or more light sources (which may be LEDs, OLEDs, SLDs, lasers, and combinations thereof) that emit light at the desired wavelength, as well as an optional driver, optional one or more sensors, and an optional command module.

[0023] The light may be administered in any manner that allows the light to pass through the skin and into the brain. Examples include intracranial administration, delivery through the scalp, such as by using a therapeutic helmet or cap, delivery to the eye, such as by using glasses that shine light through the eyelids, or by shining light from a screen, intranasal delivery, such as by a light source inserted into the nostril, delivery to the ear, delivery to a location remote from the brain, such as through skin overlying a bone, delivery to a user sitting in an enclosure, delivery to a panel, which may be flat or curved, shining the light onto the user's body, delivery to the blood, delivery to the skin, delivery to a body cavity, such as the throat, a "wearable" device for irradiating the skin, a probe designed to penetrate the skin and deliver light subcutaneously, a biocompatible implant implanted under the scalp, a transcutaneous irradiation module, and combinations thereof.

[0024] Representative disorders that can be treated include Pick's disease, Alzheimer's dementia, Lewy body dementia, primary progressive aphasia, Huntington's disease, Parkinson's disease, multiple sclerosis, multi-infarct dementia, brain damage caused by trauma, brain damage caused by hypoxia, cerebrovascular accident, central nervous system pathology caused by heavy metal poisoning, trisomy 21, viral encephalitis, viral meningitis, attention deficit hyperactivity disorder (ADHD), learning disabilities, autism, schizophrenia and depression.

[0025] In some embodiments, a lighting device including a light source (e.g., one or more LEDs and / or lasers), a timer, a sensor, and a control device is designed to be mounted or positioned near the user's head so that when the user sits, rests, or sleeps, the device automatically illuminates the head with near infrared light (NIR) and / or other colored light to reduce or delay the onset of symptoms of cognitive disorders (e.g., Alzheimer's disease or dementia), movement disorders (e.g., Parkinson's disease), and behavioral / emotional disorders (e.g., depression and schizophrenia). In some embodiments, the device may additionally include visible light illumination for timely general illumination. In some embodiments, the device is configured to be positioned so that when a person may, or is arranged to, or is detected lying in bed (or sitting in a chair), the device turns on and irradiates NIR and / or visible light on the user's head or on the area of ​​the bed or chair where the user's head is usually positioned during a selected time period. The intensity of the NIR / light is sufficient to penetrate the user's head and illuminate the user's brain, and in the case of invisible NIR, the illumination will not distract or wake the user.

[0026] NIR entering the brain through the skull can delay or improve symptoms of AD (Alzheimer's disease), other cognitive disorders, and various behavioral / mood disorders and movement disorders.

[0027] Photobiomodulation therapy is defined as a form of light therapy that utilizes non-ionizing light sources, including lasers, light-emitting diodes, and / or broadband light within the visible (400-700nm) and near-infrared (700-1100nm) electromagnetic spectrum. Photobiomodulation can be used on the entire body or on one or more selected parts, such as the head alone.

[0028] In some embodiments, head mounted products are used, but AD patients may find head mounted devices cumbersome and difficult to use, and may have difficulty complying with such AD treatment regimens without assistance. Some aspects of the present subject matter provide a contactless device to allow people or their loved ones to automatically illuminate their brains with NIR while they sleep without hassle, hands free convenience, and automatic compliance.

[0029] In certain embodiments described herein, the device may include any of the other features described herein as well as the additional features described below.

[0030] In some embodiments, the device is configured to automatically activate when a user is present (or likely to be present) for a preset period of time so that the user receives only a specified amount of modulated lighting per day. In some embodiments, the device includes one or more proximity sensors so that the device is activated or remotely activated when the presence of a user is detected.

[0031] In some embodiments, the device includes one or more sensors. Such sensors, if included, can be any desired sensor or combination of sensors, such as one or more of the following: one or more proximity detectors to control when and how long the device operates (e.g., a sensor configured to control lighting characteristics by detecting the presence of a person and / or detecting motion); one or more cameras configured to provide facial recognition to confirm compliance and / or remote monitoring; sensors for detecting biomarkers (pulse, respiration, brain waves, activity); sensors for detecting activity or monitoring agitation; sensors for monitoring environmental conditions, such as ambient temperature, ambient humidity, ambient light levels, ambient noise, music, etc., with components such as microphones, cameras, temperature sensors, light detectors, ultrasonic transducers; sleep monitors; GPS sensors so that the device knows its location, etc. The device can be configured so that such detection (via one or more sensors) can be used to automatically change the lighting characteristics of the device and / or such detection is relayed to a remote caregiver who may then adjust the lighting characteristics. The sensor (or sensors), if provided, may be integrated into the device (e.g., a built-in microphone or built-in camera for facial recognition or recording compliance) or may be remote (e.g., a chest-mounted pulse sensor, or a wrist-mounted pulse monitor).

[0032] In some embodiments, the device includes one or more timers such that the device illuminates the user's head or an area near the user's head for an "on time," and after such on time has elapsed, the illumination is turned off and remains off until a new user is detected and / or an appropriate "off time" has elapsed so that the user does not overuse the therapy.

[0033] In some embodiments, the device includes one or more timers. The timer can be configured so that it can be set to turn on at a specific time of the day, turn off at a specific time of the day, remain on for a specific length of time, etc. The timer can also be configured so that it can be set to automatically run the device at a preset time during the day or night. In addition to the timer for controlling the duration and repetition schedule of the therapeutic lighting, the device can also use a real-time clock and the actual time of day / night and a calendar so that the device can control the lighting schedule. For example, a schedule of twice a day, 5 days a week, and a total of 20 days can be used. In addition, such a clock can also control the color of the secondary visible light, thereby adjusting the amplitude and spectral composition of the visible light based on the time of night. For example, the device can be configured so that if the device is turned on at midnight, the light level will be low and the CCT will be warm, so that the user's melanopsin level remains suitable for sleep; conversely, if the device is turned on in the morning, it can illuminate at a high illuminance level and have a higher CCT to provide alertness and wakefulness.

[0034] In some embodiments, the device is configured to be mounted on a bed or near the end of a bed (or chair), and the device is configured to emit light in the area where the head (and / or other body parts) are located. For example, a suction cup, The device is mounted by clips, screws, bolts, straps, adhesives, bracket attachments, etc. The device can be located under a pillow, under a mattress, inside a pillow, or inside a mattress. The device can be made as an integral part of a bed or chair, for example, it can be built into a bed or chair.

[0035] For example, a representative specific embodiment of the device is a device that is configured to "know" the time and emit any specific electromagnetic radiation (or combination of electromagnetic radiation) during a specific time period (or multiple periods) during the day (or night) based on the selections set on the device that are tailored to the user. For example, the device can be configured to turn on for 20 minutes at 2:00 am every other day.

[0036] In some embodiments, the device includes one or more control features. Such control features can be any suitable control that can be activated in any suitable manner, such as by voice, gesture, remote control IR, Bluetooth, smartphone app, by touch (such as an operable switch or control button that can be triggered by touch, such as a control button at any suitable location on the device, such as on a light-emitting portion of the device or on a control unit of the device), etc. Such control features (if included) can be used for any desired control, such as a cut-off (on / off), a light switch that turns on visible light for reading, a control for turning on a night light, etc.

[0037] In some embodiments, the device includes one or more audio components. Such audio components (if included) can be, for example, circuits, audio speakers, or transducers that detect speech and respond to voice commands to provide audio responses or instructions to the user. Such audio components (if included) can be configured so that a remote caregiver can use them to talk to the user.

[0038] In some embodiments, the device comprises means for sending and receiving data, for example using IR, Bluetooth or WIFI.

[0039] In some embodiments, the device comprises one or more batteries, and / or wherein the device is configured to be connected directly to an external power source or to a wall socket via a power converter.

[0040] In some embodiments, the device includes electromagnetic radiation emitters (e.g., lasers or LEDs (light emitting diodes)) mounted on different surfaces of the device, including, for example, NIR LEDs on one or more surfaces of the device facing the user; a combination of NIR and visible light LEDs on one or more surfaces of the device facing the user; NIR and / or visible on one or more surfaces of the device facing the user, and other visible LEDs on one or more surfaces of the device facing away from the user (e.g., to illuminate the surrounding area or ceiling, etc.).

[0041] In some embodiments, the device is configured to have a desired radiation emission pattern, for example, where the device is configured to have (1) a narrow radiation emission pattern such that some radiation is directed to a selected area in a narrow beam (e.g., NIR is projected in a narrow beam onto a user's head), and (2) light emitted by one or more red, amber, or white emitters is directed at a wide angle and projected toward the ceiling to provide ambient lighting.

[0042] In some embodiments, the device is configured to modulate the emission of electromagnetic radiation. For example, such modulation (if included) may include multiple modulation methods superimposed, and it may be synchronized in real time to biomarkers such as brain waves, breathing, pulse, external audio sounds, etc. Such modulation (if included) may be provided in any suitable manner, such as by using (PWM) pulse width modulation, for pulse widths of 0 to 100% at frequencies from 1 Hz to 10 Khz (typically 5 Hz to 100 Hz), and / or by using amplitude modulation, from 0 to 100% and frequencies from .000001 Hz (per week) to 10 Khz. LEDs of different colors or types or positions in the device may be modulated differently at the same time, for example, a NIR LED directed toward the head may have a 30 Hz modulation with 100% amplitude, while a visible light directed toward the ceiling may have a 100% pulse width (non-pulsed) at a low, slow amplitude synchronized with the user's breathing to create a visually relaxing ambient effect.

[0043] In some embodiments, the device includes one or more additional lighting functions. Such additional lighting functions, if included, may include the device being configured to emit a mix or combination of NIR and visible light (in some cases, synchronized with brain waves using biofeedback to improve sleep patterns by providing ambient light modulation and / or synchronized light modulation in the sleep cycle). Such additional lighting functions, if included, may also include the device being configured to emit other wavelengths, such as which can be used when the user is not sleeping, such as providing bright blue-rich white light in the morning for awakening alertness, and / or colored light doses to improve skin tone - red for circulation, yellow and green for collagen, and blue for reducing bacteria.

[0044] Further additional functionality includes, for example, embodiments in which the device comprises a room light, a night light, a toilet light, a reading light, a wake-up light, a noise generator (e.g., white noise to aid sleep, calming noise for relaxation), or in which the device is configured to perform data logging (e.g., the device may include a data store to record its usage time (and the emissions provided during each such use), a data store to save user pictures, user (or multiple users) activities and vital signs, etc.).

[0045] Devices and methods consistent with the present inventive subject matter can provide numerous benefits to anyone, and in some cases, provide particularly significant benefits to patients with AD and / or dementia, the elderly, students, people with busy lifestyles (e.g., using NIR to improve sleep), and gamers (e.g., using NIR to improve performance).

[0046] In some embodiments, for example, using the technology disclosed in U.S. Patent No. 9,403,030, for example, visible light or infrared light with a wavelength between about 630 and about 910 nm is delivered to the bone marrow to treat subjects suffering from or developing Alzheimer's disease. Radiation is delivered to a portion away from the brain at a dose sufficient to cause stimulated mesenchymal stem cells to appear in the brain and degrade beta-amyloid plaques. The light applied can be coherent or incoherent, and can be applied percutaneously or directly (on the skeleton) with IR and other wavelengths. The bone can be a tibia, pelvic girdle, upper limb, upper limb girdle, rib, vertebra and / or sternum.

[0047] In other embodiments, the light therapy described herein is provided in combination with ketamine, which upregulates neurotrophic factors and improves mitochondrial function, for example, using the technology disclosed in U.S. Pat. No. 9,950,189. In one aspect of this embodiment, the dose of ketamine is a subanesthetic dose of 0.01-5 mg / kg body weight.

[0048] In other embodiments, instead of or in addition to applying light directly to the scalp to penetrate the scalp and provide light to the brain, the light can be applied subcutaneously, into a body cavity, or into the bloodstream. The mouth, ears, and nose constitute suitable body cavities for delivering light to the brain.

[0049] In some embodiments, in addition to applying light, additional treatments may include traditional Chinese medicine / color acupuncture, stimulating acupuncture / trigger points (1-40mm), Fenghan channel hyaluronic acid / stem cell therapy, behavioral health / psychiatric treatments (cognitive behavioral, biofeedback, EMDR, deep relaxation, etc.).

[0050] In another embodiment, in addition to the treatment described herein, a frequency of about 30 Hz to about 50 Hz, and more specifically about 40 Hz chronic visual stimulation is delivered to the subject non-invasively to entrain gamma oscillations in multiple brain regions of the subject, including the prefrontal cortex (PFC) and the hippocampus. Entrained gamma oscillations regulate neuronal activity in multiple brain regions (e.g., promoting functional binding of neural networks at low gamma frequencies) to induce various neuroprotective effects (e.g., improving amyloid plaques and τ (tau) hyperphosphorylation) and reduce neurodegeneration. Neuronal activity mediated by chronic visual stimulation reduces immune responses in microglia and improves abnormally modified genes and proteins involved in membrane transport, intracellular transport, synaptic function, neuroinflammation, and DNA damage responses. Behavioral changes including enhanced learning and memory were observed.

[0051] In addition to the light therapy described herein, magnetic therapy, such as PEMF, may also be administered.

[0052] These treatments can be combined with drug therapy. Representative drug therapies include anticancer agents, anti-amyloid drugs (e.g., β-secretase inhibitors), anti-inflammatory drugs (e.g., nonsteroidal anti-inflammatory agents, anti-complement agents (e.g., properidine, C3, MASP-2, C5 inhibitors), antipsychotics / antidepressants, compounds for the treatment of movement disorders, such as levodopa, etc.

[0053] There are many ways to assess the effectiveness of the methods described herein. For example, treatment can be tracked by tracking blood pressure, blood flow, pulse, heart rate variability, blood oxygen saturation, electrocardiographic response, respiratory rate, breathing pattern, galvanic skin response, pupil dilation, trabeculae-ciliary process distance, magnetic resonance imaging, brain waves, body movement, muscle tension, self-report and combinations thereof. The progression of many cognitive disorders is associated with blood, CSF or plasma protein, enzyme or metabolite concentrations, which can be used to assess treatment efficacy.

[0054] When used to treat cognitive disorders, standard tests can be used to assess cognitive changes in the subject, such as testing memory, problem-solving skills, etc. When used to treat behavioral disorders, standard psychological assessments can be used to measure progress. When used to treat movement disorders, doctors can assess changes in the severity of movement disorders.

[0055] In addition, imaging techniques are ideally performed on the patient's brain before and after treatment to monitor the effectiveness of the treatment and / or the progression of the disease. For example, a first PET or SPECT neuroimaging scan may be performed on the patient and the area of ​​the patient's brain to be treated may be identified. Ideally, this information may be used to help target the application of light to the area so identified. After treatment, either immediately or some time later, a second PET or SPECT scan may be performed and the results of the two scans compared to compare changes in the patient's brain in response to the treatment.

[0056] As disclosed in U.S. Publication No. 20080033412, feedback from one of a spectrophotometer and a patient physiological monitoring system can be used to track and / or adjust treatment. This can help determine the minimum effective irradiation light dose for a treatment course for a particular patient. An internal target area of ​​a patient affected by a pathology can be identified, and an externally accessible area of ​​the patient near the internal target area can be irradiated with light of a given wavelength, flux, and integrated flux. Feedback can then be received from one of a spectrophotometer and a patient physiological monitoring system, and the amount of light applied can be adjusted until the desired effect is achieved.

[0057] Certain metabolites are associated with specific CNS disorders, and patients can be assessed for the presence of these metabolites before and after treatment. This is particularly valuable for monitoring the progression of brain dysfunction. For example, various metabolites are known to be associated with Alzheimer's disease (Greenberg et al., "A proposed metabolic strategy for monitoring disease progression in Alzheimer's disease," Electrophoresis. 2009Apr; 30(7): 1235-9 and Palmqvist et al, "Discriminative Accuracy of Plasma Phospho-tau217 for Alzheimer Disease vs Other Neurodegenerative Disorders" JAMA. Published online on July 28, 2020. doi: 10.1001 / jama.2020.12134), and the concentration of one or more of these metabolites can be tracked over time.

[0058] A more complete understanding of the inventive subject matter may be obtained with reference to the accompanying drawings and the following detailed description of the inventive subject matter. BRIEF DESCRIPTION OF THE DRAWINGS

[0059] Figure 1 A first embodiment of an electromagnetic radiation emitting device according to the inventive subject matter is schematically depicted.

[0060] Figure 2 is along Figure 1 Sectional view along line II-II.

[0061] Figure 3 An embodiment of an electromagnetic radiation emitting device according to the inventive subject matter is schematically depicted, attached to a chair, with a patient seated in the chair.

[0062] Figure 4 An embodiment of an electromagnetic radiation emitting device according to the inventive subject matter is schematically depicted, together with a human head positioned proximate thereto.

[0063] Figure 5 An embodiment of an electromagnetic radiation emitting device according to the inventive subject matter is schematically depicted attached to a bed with a patient lying on the bed.

[0064] Figure 6 A circuit for an embodiment of an electromagnetic radiation emitting device according to the inventive subject matter is schematically depicted (as a block diagram).

[0065] Figure 7Additional circuitry for an embodiment of an electromagnetic radiation emitting device according to the inventive subject matter is schematically depicted (as a block diagram).

[0066] Figure 8 Another embodiment of an electromagnetic radiation emitting device according to the inventive subject matter is schematically depicted.

[0067] Fig. 9 Another embodiment of an electromagnetic radiation emitting device according to the inventive subject matter is schematically depicted.

[0068] Fig.10 An embodiment of an electromagnetic radiation emitting device according to the inventive subject matter, comprising a stand, is schematically depicted, wherein a person's head is close to the electromagnetic radiation emitting device.

[0069] Fig.11 An embodiment of an apparatus 110 within the scope of this twelfth aspect is depicted.The apparatus 110 comprises a plurality of electromagnetic radiation emitters and a mounting structure 111.

[0070] Fig.12 An embodiment of an apparatus described herein is schematically depicted, comprising a plurality of electromagnetic radiation emitters and a mounting structure 121 . DETAILED DESCRIPTION

[0071] Disclosed are devices and methods for treating central nervous system disorders using light of various wavelengths. Representative central nervous system disorders include cognitive disorders, movement disorders, and behavioral / emotional disorders. In some embodiments, a combination of light wavelengths is used. In some aspects of these embodiments, a first wavelength of light is applied at a wavelength that provides an anti-inflammatory effect, and a second wavelength of light is applied at a wavelength that provides increased angiogenesis, by promoting endogenous NO production and / or release in the brain.

[0072] The present invention will be better understood with reference to the following definitions.

[0073] definition

[0074] Statement: "Cannot emit radiation greater than 50mW / cm 2 "An electromagnetic radiation emitting device that emits near-infrared light" means that no matter what kind of electrical energy (voltage and current) is provided to the electromagnetic radiation emitting device, the electromagnetic radiation emitting device does not emit a radiation greater than 50 mW / cm 2 near-infrared light (and this statement does not mean that the electromagnetic radiation emitting device cannot emit other electromagnetic radiation, that is, electromagnetic radiation other than near-infrared radiation at any radiance, that is, "cannot emit radiance greater than 50mW / cm 2"Near-infrared electromagnetic radiation emitting devices" include (1) devices (and components) that emit only near-infrared light, and (2) devices (and components) that are capable of emitting near-infrared light and radiation with wavelengths outside the near-infrared wavelength range.

[0075] The term "electromagnetic radiation emitting device configured to emit radiation containing a radiation intensity of at least 1 mW / cm 2 "Near-infrared electromagnetic radiation" means that there is a magnitude of electrical energy (voltage and current) that can be supplied to an electromagnetic radiation emitting device, at which magnitude the electromagnetic radiation emitting device will emit a radiance of at least 1 mW / cm 2 near-infrared light (and this statement does not mean that the electromagnetic radiation emitting device cannot emit other electromagnetic radiation, that is, electromagnetic radiation other than near-infrared radiation at any radiance, that is, "configured to emit including radiance of at least 1 mW / cm 2 "Electromagnetic radiation emitting devices that emit near-infrared electromagnetic radiation" include (1) devices (and components) that emit only near-infrared light and devices (and components) that emit near-infrared light, and (2) devices (and components) that are capable of emitting near-infrared light and radiation with wavelengths outside the near-infrared wavelength range.

[0076] The expression "emitter" refers to any component or device (eg, an LED) configured to emit electromagnetic radiation.

[0077] The expression "on..." as used herein (for example, in the expression "a first electromagnetic radiation emitter (1) is on a first piece of furniture...") means that the first structure "on" the second structure may be in contact with the second structure, or may be separated from the second structure by one or more intermediate structures (each side or opposite sides of the intermediate structure is in contact with the first structure, the second structure or one of the intermediate structures).

[0078] As used herein, the expression “partially in…” (for example, in the expression “the first electromagnetic radiation emitter…(2) is partially in…the first piece of furniture”) means that a portion of the first structure (which is “partially in the second structure”) is located in a recessed area (i.e., a depression, a recessed space, a groove, etc.) of the second structure.

[0079] As used herein, the expression “entirely within” (for example, in the expression “the first electromagnetic radiation emitter…(3) is entirely within the first piece of furniture”) means that the entirety of the first structure (which is “entirely within the second structure”) is located within a recessed area (i.e., a depression, a recessed space, a groove, etc.) of the second structure.

[0080] The expression "sensor" refers to any sensor or detector (which may be a device or component), including but not limited to an identity sensor, a human body sensor, a feature sensor, a head sensor, a head orientation sensor (head orientation sensor, head direction sensor), a facial sensor, a brain wave sensor, a pulse sensor, a breathing sensor, a body temperature sensor, a blood pressure sensor, an oxygenation sensor, a skin resistance sensor, a skin temperature sensor, a motion sensor, an eye state sensor, a body motion sensor, an apparel detector, an ambient temperature sensor, an ambient humidity sensor, an ambient noise sensor, a global positioning sensor, an ambient light sensor, a motion detector, a camera and a microphone. Those skilled in the art are familiar with such sensors, and such sensors are available, and any such sensor can be used as a sensor according to the subject matter of the present invention.

[0081] The expression “detection range” refers to the distance at which a person or object can be spaced apart from a sensor or detector and the detector can sense or detect a phenomenon, characteristic or parameter of the person or object that the sensor or detector is configured to sense or detect.

[0082] The expression “identity sensor” refers to a device or component that [i] detects whether a particular person is within a detection range of the identity sensor and / or [ii] determines the identity of a person within the detection range of the identity sensor.

[0083] The expression "human body sensor" refers to a device or component that detects whether a person is within a detection range of the human body sensor.

[0084] The expression "feature sensor" refers to a device or component that detects whether a person within the detection range of the feature sensor has a feature or a set of features (such as facial features or size features) that matches a stored feature or a set of stored features.

[0085] The expression “head sensor” refers to a device or component that detects whether a human head is within the detection range of the identity sensor.

[0086] The expression "head orientation sensor" refers to a device or component that detects the orientation of a human head relative to the head orientation sensor.

[0087] The expression "face sensor" refers to a device or component that detects whether a human face is within the detection range of the identity sensor.

[0088] The expression "weight sensor" refers to a device or assembly that detects the weight of an object or person on a surface or structure (and / or the presence of an object equal to or exceeding a certain weight) .

[0089] The expression "brainwave sensor" refers to a device or a component that detects brainwaves of a person in a confined space relative to the brainwave sensor.

[0090] The expression "pulse sensor" refers to a device or component that detects a person's pulse within a confined space relative to the pulse sensor.

[0091] The expression "breathing sensor" refers to a device or component that detects the breathing of a person in a confined space relative to the breathing sensor.

[0092] The expression “body temperature sensor” refers to a device or component that detects the body temperature of a person in a confined space relative to the breathing sensor.

[0093] The expression "blood pressure sensor" refers to a device or component that detects the blood pressure of a person in a confined space relative to the blood pressure sensor.

[0094] The expression "oxygenation sensor" refers to a device or a component that detects the oxygenation of a person in a defined space relative to a breathing sensor.

[0095] The expression "skin resistance sensor" refers to a device or component that detects the skin resistance of a person in a confined space relative to the skin resistance sensor.

[0096] The expression "skin temperature sensor" refers to a device or component that detects the skin temperature of a person in a confined space relative to the skin temperature sensor.

[0097] The expression "motion sensor" refers to a device or component that detects the motion of a person in a defined space relative to the motion sensor.

[0098] The expression "vibration sensor" refers to a device or component that detects vibrations, eg vibrations having at least a certain amplitude (eg which may be selected).

[0099] The expression "impact sensor" refers to a device or component that senses impact (eg, punching, clapping, kicking, etc.).

[0100] The expression "eye state sensor" refers to a device or component that detects the state of a person's eyes in a confined space relative to the eye state sensor, such as whether any eye of the person is open, closed, blinking, the frequency of blinking, the duration of eyes closed during a sequence, and the duration of eyes open during a sequence.

[0101] The expression "body motion sensor" refers to a device or component that detects specific body movements of a person in a confined space relative to the body motion sensor, such as turning over, arm movement, leg movement, chest movement, shrinking, rubbing the eyes with fingers, gestures (such as waving, nodding, etc.), repetitive movements (such as restlessness), etc.

[0102] The expression "clothing detector" refers to a device or component for detecting whether a person within a defined space relative to the clothing detector is wearing a specific clothing or a piece of clothing, such as a hat, glasses, eye mask, earplugs, etc.

[0103] The expression "ambient temperature sensor" refers to a device or component that detects the temperature within a defined ambient space relative to the ambient temperature sensor.

[0104] The expression "ambient humidity sensor" refers to a device or component that detects humidity within a defined ambient space relative to the ambient humidity sensor.

[0105] The expression “ambient light sensor” refers to a device or component that detects light incident on the ambient light sensor (eg, the presence of light of a specific wavelength or a specific wavelength range, the radiance of light, the radiance of a specific wavelength or wavelength range).

[0106] The expression “environmental noise sensor” refers to a device or component that detects noise at the environmental noise sensor (eg, the presence or absence of noise at a specific wavelength or a specific wavelength range, the amplitude of noise, the amplitude of a specific wavelength or a wavelength range).

[0107] The expression "GPS" (or "global positioning sensor") refers to a device or component that detects the position of the sensor relative to the earth. Those skilled in the art are familiar with such sensors, and such sensors are available, and any such sensor can be used as a GPS according to the subject matter of the present invention.

[0108] The expression "motion detector" refers to a device or assembly that detects the motion of a person in a defined space relative to the motion detector. A person skilled in the art is familiar with such detectors, and such detectors are available, and any such detector can be used as a motion detector according to the subject matter of the invention.

[0109] The expression "camera" refers to a device or assembly that detects (and optionally also records, e.g., digitally) visual images as they appear from the camera's vantage point. Those skilled in the art are familiar with cameras, and such cameras are available, and any such device or assembly may be used as a camera according to the subject matter of the present invention.

[0110] The expression "microphone" refers to a device or component that detects sound received at the microphone location (and optionally also records, e.g. digitally). The skilled person is familiar with microphones, and such microphones are available, and any such device or component can be used as a microphone according to the subject matter of the invention.

[0111] The expression "plane tangent to a first point" (and similar expressions) with respect to a surface refers to the plane that is most tangent to the particular point. That is, even if a point does not have a perfect tangent plane (and perhaps no plane is even close to a perfect tangent plane), the tangent plane can be defined by an imaginary segment of a plane that is circular and has a diameter of 1 cm, i.e., touches the surface at the center of the circle, and where the circle is divided into six slices of equal size (60 degrees), and for each slice, at locations 0.25 cm, 0.50 cm, 0.75 cm, and 1 cm from the center of the circle along the line segments defined by the slice edges and along the three line segments that divide the slice into four equal sub-slices (i.e., at 15 degrees, 30 degrees, and 45 degrees), the sum of the distances between the slice and the surface is equal to the total value of the slice, and the sum of the following is minimized: the total value of the first slice divided by the total value of the second slice, the total value of the second slice divided by the total value of the third slice, the total value of the third slice divided by the total value of the fourth slice, the total value of the fourth slice divided by the total value of the fifth slice, the total value of the fifth slice divided by the total value of the sixth slice, and the total value of the sixth slice divided by the total value of the first slice.

[0112] The expression "actuator" refers to a device or structure that is configured to be actuated by being pressed (eg, a button or lever) or by receiving an electronic signal.

[0113] The expression "attachment feature" refers to any structure, property, or material (or a combination of one or more structures, and / or one or more properties, and / or one or more materials) that is capable of holding an electromagnetic radiation emitting device in place relative to the structure in which the attachment feature is located (or to which the attachment feature is attached). Representative examples of attachment features include suction cups, adhesives, magnets, screw holes, and bolt holes.

[0114] The expression "direction" as used herein (for example in the expression "a first emitting ray axis extending in a first direction") refers to the orientation of a line (or line segment or ray) and any other line (or line segment or ray), i.e., for any two directions equal thereto, the acute angle defined by the two directions has only one value (unless the two directions are identical or defined as right angles relative to each other).

[0115] The expression "determines the identity of a person within the detection range of the first sensor" (etc.) means that the apparatus can determine the identity of at least one person, but not necessarily the identity of every person.

[0116] The expression "is configured to emit" (e.g. in the expression "a first electromagnetic radiation emitter is configured to emit a first electromagnetic radiation emitter having a power of at least 1 mW / cm 2The term "radiance of NIR electromagnetic radiation" refers to the device being "configured to emit" having a power line (to which power can be supplied to power the device), and when a line voltage is supplied to the power line, the characteristics described as characteristics of the device configuration will occur (e.g., at a first position, the radiance will be 0.5 mW / cm 2 Up to 5mW / cm 2 (The expression "line voltage" is used herein according to its well-known usage to refer to standard electricity (120V) provided by an energy source, such as electricity provided by the power grid, including AC and DC).

[0117] As used herein in connection with light output from one or more electromagnetic radiation emitters, the expression "emission ray axis" refers to a ray originating from the electromagnetic radiation emitter and extending in the direction of maximum brightness of the light emission or in the average direction of the light emission (in other words, in the case of the average direction of the light emission, (1) if a light emitter is provided wherein the brightness distribution of the emitted light is non-Lambertian, for example, if the brightness distribution of the emitted light is annular (e.g., the light emitter itself may be annular or ring-shaped, or a plurality of light emitters may be arranged in a ring or ring pattern), for example, the direction of maximum brightness extends around the ring in the form of a circle extending around the polar axis, for example, in a C-type coordinate system at approximately 120 degrees vertically (and around a full 360 degrees) degrees laterally extending from one direction to another, i.e. defining a circle), i.e. where the polar axis is vertical, the vertical angle ranges from 0 degrees (nadir) to 180 degrees (zenith) (90 degrees vertical is the equator), and the lateral angle ranges from 0 degrees to 360 degrees, the emission ray axis may coincide with the vertical axis (for example because the average direction of the maximum value lies on the vertical axis), even if the direction of maximum brightness itself does not lie on the vertical axis, or (2) if the maximum brightness is in a first direction, but the brightness in a second direction ten (or fifty) degrees to one side of the first direction is greater than the brightness in a third direction ten (or fifty) degrees to the opposite side of the first direction, then as a result of the brightness in the second and third directions, the average direction of light emission will be slightly shifted toward the second direction).

[0118] The expression "independently" (for example in the expression "one or more of the electromagnetic radiation emitters emit electromagnetic radiation independently of whether any other electromagnetic radiation emitter emits electromagnetic radiation") means that the device can be operated in such a way that one or more of the electromagnetic radiation emitters can emit electromagnetic radiation while one or more other electromagnetic radiation emitters do not emit electromagnetic radiation, and / or whether one or more electromagnetic radiation emitters are emitting electromagnetic radiation (and / or are changing whether to emit electromagnetic radiation) is not affected (or limited) by whether one or more other electromagnetic radiation emitters emit electromagnetic radiation.

[0119] The expression "cognitive activities" refers to activities that require some degree of thinking, such as higher-order thinking, such as meeting people, doing chores, solving math problems, solving puzzles, playing games, and so on.

[0120] The expression "radius of curvature" refers to the radius of a circle (e.g. at a point of the surface where the cross section of the surface corresponds exactly to the surface of a portion of a circle) which touches the cross section of the surface at this point and has the same tangent and curvature at this point. In case the cross section of the surface area between the first substantially flat portion and the second substantially flat portion (e.g. the cross section of the edge between two substantially flat portions of a protrusion) is not exactly circular and / or is not continuously curved:

[0121] The radius of curvature of this area of ​​this surface is the radius of a circle having a first point (having a first tangent) and a second point (having a second tangent), wherein [1] the first tangent defines an angle with respect to the second tangent that is equal to the angle formed by the first substantially flat area with respect to the second substantially flat area, and [2] the closest corresponding points on the first substantially flat portion and the second substantially flat portion are separated by a distance substantially equal to the distance separating the first point on the circle from the second point on the circle,

[0122] and / or

[0123] The radius of curvature of a portion of this cross-section of this surface region (the portion extending from a first position on the surface to a second position on the surface) is the radius of a circle having a first point (having a first tangent) and a second point (having a second tangent), wherein [3] the first tangent defines an angle relative to the second tangent that is substantially equal to the angle defined by the tangent at the first position relative to the tangent at the second position, and [4] the first position is separated from the second position by a distance substantially equal to the distance separated from the first point on the circle by the second point on the circle.

[0124] The subject matter of the present invention includes many combinations of elements and features. The expression "in some embodiments, it may suitably include or exclude any other features described herein" etc. is used in this specification to introduce elements and / or features of the subject matter of the present invention, which may or may not be included in any particular embodiment, i.e., elements and / or features that can be combined in any suitable manner. In other words, the subject matter of the present invention includes all combinations of elements and / or features introduced by the expression "in some embodiments according to the subject matter of the present invention, it may suitably include or exclude any other features described herein" etc.

[0125] A light emitting diode ("LED") is a combination of one or more LED components, including but not limited to an electroluminescent semiconductor material, a substantially translucent package, a current conductor, a voltage insulator, a photon emission path, a power source, an LED heat sink, an array of electroluminescent semiconductor materials, an addressable array of electroluminescent semiconductor materials, a bonding material, a wire bonding material, LED component fasteners, and an LED integrated circuit. The photon emission path is composed of one or more combinations of photon emission path components, including but not limited to a translucent optical lens and a wavelength-dependent photon filter. The LED is selected from one or more LED types, including but not limited to laser diodes, organic light emitting devices, semiconductor LED types based on Group IV of the periodic table, semiconductor LED types based on Group III-V of the periodic table, semiconductor LED types based on Group II-VI of the periodic table, optically pumped LED types, electrically pumped LED types, and organic light emitting device types. LED types based on Group IV elements include but are not limited to LED types based on germanium, silicon, carbon nanotubes, silicon carbide ("SiC"), and diamond. Group III-V LED types include, but are not limited to, those based on aluminum nitride ("AlN"), gallium nitride ("GaN"), aluminum phosphide ("AlP"), gallium phosphide ("GaP"), aluminum selenide ("AlSe"), gallium selenide ("GaSe"), and aluminum indium gallium nitride ("AlInGaN"). Group II-VI LED types include, but are not limited to, those based on zinc oxide, zinc sulfide, zinc selenide, zinc telluride, cadmium oxide, cadmium sulfide, cadmium selenide, and cadmium telluride. The exact random ratios of the elements and the doping process are well known in the literature and need not be repeated herein.

[0126] The apparatus and method are described in more detail below.

[0127] I. Passive therapy

[0128] In one embodiment of the devices described herein, light is applied to a subject in need of treatment without physically contacting the device with the subject. This therapy is passive because it can occur without intentional treatment effort by the user. This passive approach has many benefits, but is particularly beneficial for treatment compliance. Various embodiments of electromagnetic radiation emitting devices are discussed below. These devices are particularly advantageous because they can achieve therapeutic benefits without relying on treatment compliance.

[0129] In each embodiment, the device can include any suitable components or features (including any combination thereof) described in conjunction with any aspect of the subject matter of the present invention. For example, the device can be configured to be installed on furniture (e.g., a bed, a chair, a mattress, a pillow, etc.), partially installed in furniture, or completely installed in furniture.

[0130] These devices have a variety of uses, one of which is to provide treatments, such as NIR treatments and / or other wavelengths of light, that are tailored to the specific characteristics of the user and / or environment in a manner that is not invasive or annoying to the user / patient (thereby increasing the likelihood of compliance). Since the device is not attached to the user / patient, this can allow the user / patient to engage in other activities, which is one way that the device can increase the likelihood of compliance.

[0131] Where the device includes a sensor, the sensor may be any type of sensor. Representative sensors include identity sensors, human body sensors, feature sensors, head sensors, head orientation sensors, facial sensors, weight sensors, brain wave sensors, pulse sensors, respiration sensors, body temperature sensors, blood pressure sensors, oxygenation sensors, skin resistance sensors, skin temperature sensors, motion sensors, vibration sensors, shock sensors, eye state sensors, body motion sensors, clothing detectors, ambient temperature sensors, ambient humidity sensors, ambient light sensors, ambient noise sensors, GPS (global positioning sensors), motion detectors, cameras, and / or microphones, each type of sensor being as defined herein.

[0132] In a first aspect, the device is an electromagnetic radiation emitting device that is not in physical contact with a subject and comprises: at least a first electromagnetic radiation emitter; and at least a first sensor, the first electromagnetic radiation emitter being configured to emit a radiation having a radiation intensity of at least 1 mW / cm 2 (In some embodiments at least 2 mW / cm 2 , at least 3mW / cm 2 , at least 4mW / cm 2 , at least 5mW / cm 2 , at least 6mW / cm 2 , at least 7mW / cm 2 , at least 8mW / cm 2 , at least 9mW / cm 2 , at least 10mW / cm 2 , at least 12mW / cm 2 , at least 15mW / cm 2 , at least 20mW / cm 2 , at least 25mW / cm 2 , at least 30mW / cm 2 , at least 35mW / cm 2 , at least 40mW / cm 2 or at least 45mW / cm 2 ) near-infrared light (hereinafter referred to as "NIR") electromagnetic radiation, wherein the first electromagnetic radiation emitter cannot emit a radiance greater than 50 mW / cm 2NIR (in some embodiments, 45 mW / cm 2 , 40mW / cm 2 、35mW / cm 2 、30mW / cm 2 , 25mW / cm 2 , 20mW / cm 2 、15mW / cm 2 , 12mW / cm 2 、10mW / cm 2 , 9mW / cm 2 , 8mW / cm 2 , 7mW / cm 2 、6mW / cm 2 , 5mW / cm 2 , 4mW / cm 2 、3mW / cm 2 or 2mW / cm 2 ).

[0133] Therapy may be customized to target specific characteristics of the user and / or environment and / or to achieve particular user / patient compliance.

[0134] In some embodiments, the first sensor is a head orientation sensor, the electromagnetic radiation emitting device includes multiple electromagnetic radiation emitters, including the first electromagnetic radiation emitter, and the electromagnetic radiation emitting device adjusts which of the multiple electromagnetic radiation emitters emits NIR and / or the corresponding luminosity of NIR emitted by the multiple electromagnetic radiation emitters based on the orientation of the human head detected by the first sensor.

[0135] In some aspects of these embodiments, based on the orientation of the human head, the electromagnetic radiation emitting device adjusts which of the multiple electromagnetic radiation emitters emits NIR and / or the corresponding brightness of the NIR emitted by the multiple electromagnetic radiation emitters to provide a substantially uniform dose around the human brain (or a specific dose variation around the human brain), or delivers NIR to a specific portion (or multiple portions) of the human brain.

[0136] In a second aspect, the device comprises: at least first, second, third, fourth and fifth electromagnetic radiation emitters, each of the first, second, third, fourth and fifth electromagnetic radiation emitters being configured to emit NIR, the electromagnetic radiation emitting device being configured to emit at a first position a radiation having a radiance of about 0.5 mW / cm 2 to about 5mW / cm 2 The first position is spaced 10 cm or more from the electromagnetic radiation emitting device.

[0137] In some embodiments, the device comprises no more than 60 electromagnetic radiation emitters.

[0138] In a third aspect, the apparatus comprises: at least a first electromagnetic radiation emitter; and at least a first sensor, wherein the first electromagnetic radiation emitter is configured to emit electromagnetic radiation comprising NIR.

[0139] In some embodiments: the first sensor is an identity sensor, the electromagnetic radiation emitting device is configured to store treatment information including the date and time of NIR treatment applied to each person, and the NIR dose applied to each person during the NIR treatment, the electromagnetic radiation emitting device is configured to store protocol information including the required schedule for NIR treatment to be applied to each person, the electromagnetic radiation emitting device is configured to determine the identity of the first person within the detection range of the first sensor, the electromagnetic radiation emitting device is configured to determine whether the first person needs NIR treatment based on the detected identity of the first person, the treatment information of the first person stored in the electromagnetic radiation emitting device, and the protocol information for the first person stored in the electromagnetic radiation emitting device, and if so, NIR treatment should be applied to the first person, and / or the electromagnetic radiation emitting device is configured to, if the electromagnetic radiation emitting device determines that the first person needs NIR treatment based on the detected identity of the first person, the treatment information of the first person stored in the electromagnetic radiation emitting device, and the protocol information for the first person stored in the electromagnetic radiation emitting device, the required NIR treatment, then administer the required NIR treatment and / or other wavelength treatment to the first person.

[0140] In some embodiments: the first sensor is an identity sensor, the electromagnetic radiation emitting device is configured to determine the identity of a first person within a detection range of the first sensor based on information from the identity sensor, the electromagnetic radiation emitting device is configured to store regimen information containing required NIR treatments to be administered to each person, the electromagnetic radiation emitting device is configured to determine whether NIR treatment should be administered to the first person based on the determined identity of the first person, and the electromagnetic radiation emitting device is configured to administer the required NIR treatment to the first person based on the determined identity of the first person and the stored regimen information for the first person if the electromagnetic radiation emitting device determines that NIR treatment should be administered to the first person.

[0141] In some embodiments: the electromagnetic radiation emitting device is configured to receive an input personal identity including an input identity of a first person, the electromagnetic radiation emitting device is configured to store treatment information including a date and time of NIR treatment administered to each person, and a NIR dose administered to each person during the NIR treatment, the electromagnetic radiation emitting device is configured to store regimen information including a required agenda for NIR treatment to be administered to each person, the electromagnetic radiation emitting device is configured to determine whether the first person needs NIR treatment based on the identity of the first person, the treatment information of the first person stored in the electromagnetic radiation emitting device, and the regimen information of the first person stored in the electromagnetic radiation emitting device, and if so, NIR treatment should be administered to the first person, and the electromagnetic radiation emitting device is configured to administer the required NIR treatment to the first person if the electromagnetic radiation emitting device determines that the first person needs NIR treatment based on the input identity of the first person, the treatment information of the first person stored in the electromagnetic radiation emitting device, and the regimen information of the first person stored in the electromagnetic radiation emitting device.

[0142] In some embodiments: the electromagnetic radiation emitting device is configured to receive an input personal identity including an input identity of a first person, the electromagnetic radiation emitting device is configured to store regimen information including the desired NIR treatment to be administered to each individual, and the electromagnetic radiation emitting device is configured to administer the desired NIR treatment to the first individual based on the input identity of the first person and the stored regimen information for the first person.

[0143] In some embodiments of the third aspect of the inventive subject matter, it may or may not appropriately include any other features described herein: the first sensor is configured to detect a first person within a detection range of the first sensor, and the electromagnetic radiation emitting device is configured to administer NIR treatment to the first person when the first sensor detects that the first person is within the detection range of the first sensor.

[0144] In some embodiments, the first sensor is selected from the group of sensors consisting of a human body sensor, a head sensor, a head orientation sensor, a face sensor, a motion sensor, an eye state sensor, a body motion sensor, and a weight sensor.

[0145] In some embodiments: the electromagnetic radiation emitting device is configured to store treatment information, the treatment information including the date and time of the NIR treatment that has been applied, and the NIR dose applied to each person during the NIR treatment, the electromagnetic radiation emitting device is configured to store protocol information, the first sensor is configured to detect the first person within the detection range of the first sensor, the electromagnetic radiation emitting device is configured to determine whether the first person needs NIR treatment based on the treatment information and protocol information stored in the electromagnetic radiation emitting device, and if so, the NIR treatment that should be applied to the first person, and the electromagnetic radiation emitting device is configured to apply the required NIR treatment to the first person if the electromagnetic radiation emitting device determines that the first person needs NIR treatment based on the treatment information and protocol information stored in the electromagnetic radiation emitting device. In some such embodiments, the first sensor is selected from the group of sensors consisting of a human body sensor, a head sensor, a head orientation sensor, a face sensor, a motion sensor, an eye state sensor, a body motion sensor, and a weight sensor.

[0146] In a fourth aspect, the device comprises: at least a first electromagnetic radiation emitter; and at least a first sensor, the first electromagnetic radiation emitter being configured to emit electromagnetic radiation comprising at least one type of radiation selected from the group of radiation types consisting of: (1) visible light comprising at least one wavelength in the range of 490 nm to 500 nm, and (2) near ultraviolet light (referred to herein as "near UV light").

[0147] These devices have a variety of uses, one of which is to provide specific electromagnetic radiation therapy that produces useful effects on the human body.

[0148] In a fifth aspect, the device includes: at least a first mounting structure; and at least a first electromagnetic radiation emitter, which is configured to emit electromagnetic radiation including red visible light, each electromagnetic radiation emitter emitting red visible light is mounted on at least one of the at least first mounting structures, and the corresponding emission ray axis of each electromagnetic radiation emitter emitting red visible light does not pass through any of the at least first mounting structures.

[0149] These devices have multiple uses, one of which is to provide red light therapy in a manner that is not invasive or disturbing to the user / patient (thereby increasing the likelihood of compliance).

[0150] In some cases, the electromagnetic radiation emitting device further comprises at least a first sensor. In some such embodiments, the sensor is at least 50 mm from the object (eg, a person) illuminated by the red visible light.

[0151] In a sixth aspect, an apparatus comprises: at least a first electromagnetic radiation emitter; and at least a first actuator, the first electromagnetic radiation emitter being configured to emit electromagnetic radiation comprising red visible light when the first actuator is actuated. In some embodiments, the first actuator is a button, and in other embodiments, a timer.

[0152] In a seventh aspect, the device comprises: at least a first electromagnetic radiation emitter; and at least a first attachment feature, the first electromagnetic radiation emitter being configured to emit electromagnetic radiation comprising NIR, at least the first attachment feature being configured to hold the electromagnetic radiation emitting device relative to a first structure comprising a first and a second surface, the second surface being parallel to the first surface, and the second surface being separated from the first surface by a first distance, the first distance being in the range of 1 cm to 8 cm.

[0153] In some embodiments, the first and second surfaces are located on a piece of furniture selected from the group consisting of a headboard and a chair back.

[0154] In some embodiments, the first distance is in the range of 2cm to 8cm, 3cm to 8cm, 4cm to 8cm, 5cm to 8cm, 6cm to 8cm, 7cm to 8cm, 1cm to 7cm, 2cm to 7cm, 3cm to 7cm, 4cm to 7cm, 5cm to 7cm, 6cm to 7cm, 1cm to 6cm, 2cm to 6cm, 3cm to 6cm, 4cm to 6cm, 5cm to 6cm, 1cm to 5cm, 2cm to 5cm, 3cm to 5cm, 4cm to 5cm, 1cm to 4cm, 2cm to 4cm, 3cm to 4cm, 1cm to 3cm, 2cm to 3cm, or 1cm to 2cm.

[0155] In an eighth aspect, the device comprises: at least a first electromagnetic radiation emitter; and at least a first attachment feature, the first electromagnetic radiation emitter being configured to emit electromagnetic radiation comprising NIR, the first attachment feature being selected from the group of attachment features consisting of a suction cup, an adhesive, a magnet, a screw hole, and a bolt hole.

[0156] In a ninth aspect, the device comprises a plurality of electromagnetic radiation emitters, the plurality of electromagnetic radiation emitters comprising: at least a first NIR emitter, the first NIR emitter being configured to emit electromagnetic radiation comprising NIR, at least a first infrared light (referred to herein as "IR light") emitter, the first IR light emitter being configured to emit electromagnetic radiation comprising IR light; and at least a first UV light emitter, the first UV light emitter being configured to emit electromagnetic radiation comprising UV light.

[0157] The device can provide specific electromagnetic radiation therapy (simultaneously, sequentially, or a combination of simultaneous and sequential involving different types of radiation, for example it may include NIR and IR, NIR and UV, IR and UV, or NIR, IR and UV, and optionally visible light) that provides a useful effect on a person.

[0158] In some embodiments, the device further comprises at least a first visible light emitter.

[0159] In some embodiments, a device may include any of the other features described herein:

[0160] The electromagnetic radiation emitting device further comprises a light type selection element; and

[0161] The light type selection element is configured to enable a user to select one or more of the electromagnetic radiation emitters to emit electromagnetic radiation, independent of whether any other electromagnetic radiation emitter is emitting electromagnetic radiation, whereby the light type selection element can be used to enable the electromagnetic radiation emitting device to selectively emit any selection selected from (1) NIR light alone, (2) IR light alone, (3) UV light alone, (4) a combination of NIR and IR light, (5) a combination of NIR and UV light, (6) a combination of IR light and UV light, and (7) a combination of NIR, IR light, and UV light.

[0162] In some such embodiments: the electromagnetic radiation emitting device further comprises at least a first visible light emitter, and the light type selection element is further configured to enable a user to select one or more of the at least first visible light emitters to emit visible light, independent of whether any other electromagnetic radiation emitters emit electromagnetic radiation, whereby the light type selection element can be used to cause the electromagnetic radiation emitting device to selectively emit any of the following: (1) NIR light alone, (2) IR light alone, (3) UV light alone, (4) a combination of NIR and IR light, (5) a combination of NIR and UV light. light, (6) a combination consisting of IR light and UV light, (7) a combination consisting of NIR, IR light, and UV light, (8) a combination consisting of NIR and visible light, (9) a combination consisting of IR light and visible light, (10) a combination consisting of UV light and visible light, (11) a combination consisting of NIR, IR light, and visible light, (12) a combination consisting of NIR, UV light, and visible light, (13) a combination consisting of IR light, UV light, and visible light, (14) a combination consisting of NIR, IR light, UV light, and visible light, and (15) visible light alone.

[0163] In a tenth aspect, the apparatus comprises at least a first electromagnetic radiation emitter and at least a first piece of furniture, wherein the at least first piece of furniture is selected from the group consisting of a pillow, a mattress, a bed, and a chair; the first electromagnetic radiation emitter can be configured to emit electromagnetic radiation comprising NIR, and the first electromagnetic radiation emitter is (1) on the first piece of furniture, (2) partially in the first piece of furniture, or (3) completely in the first piece of furniture.

[0164] In the eleventh aspect, the device includes: a plurality of electromagnetic radiation emitters; and a color temperature selection element, the plurality of electromagnetic radiation emitters including: at least a first electromagnetic radiation emitter, which is configured to emit electromagnetic radiation including NIR; and at least a first variable color temperature emission element, which includes one or more variable color temperature emission element emitters, the color temperature selection element enables a user to select a desired color temperature from at least two selectable color temperatures, whereby the color temperature selection element can be used to enable the electromagnetic radiation emitting device to emit visible light of any one of the at least two selectable color temperatures.

[0165] The device can provide specific electromagnetic radiation therapy (including NIR, visible light of one or more color temperatures, or a combination of NIR and visible light of one or more color temperatures, simultaneously, sequentially, or a combination of both simultaneously and sequentially) that provides a useful effect on a person.

[0166] In some embodiments, the device may appropriately include or exclude any of the following features: the electromagnetic radiation emitting device further includes a light type selection element, and the light type selection element is configured to enable a user to select one or more of the electromagnetic radiation emitters to emit electromagnetic radiation, which is independent of whether any other electromagnetic radiation emitter emits electromagnetic radiation, whereby the color temperature selection element and the light type selection element can be used to enable the electromagnetic radiation emitting device to selectively emit any selection from the following: (1) visible light of at least one desired color temperature selected from at least two optional color temperatures alone, (2) NIR alone, and (3) a combination of visible light of at least one desired color temperature selected from at least two optional color temperatures and NIR.

[0167] In some embodiments, the color temperature selection element and the first variable color temperature emission element are configured to enable a user to select one or more desired color temperatures from at least a first color temperature to a ninth color temperature, the first color temperature being in the range of 1,000K to 2,000K, the second color temperature being in the range of 2,000K to 3,000K, the third color temperature being in the range of 3,000K to 4,000K, the fourth color temperature being in the range of 4,000K to 5,000K, the fifth color temperature being in the range of 5,000K to 6,000K, the sixth color temperature being in the range of 6,000K to 7,000K, the seventh color temperature being in the range of 7,000K to 8,000K, the eighth color temperature being in the range of 8,000K to 9,000K, and the ninth color temperature being in the range of 9,000K to 10,000K.

[0168] In a twelfth aspect, the device comprises a plurality of electromagnetic radiation emitters and at least a first mounting structure, wherein the plurality of electromagnetic radiation emitters comprise at least a first NIR emitter and at least a first visible light emitter, the first NIR emitter being configured and oriented to have a first emission ray axis relative to the first mounting structure, the first emission ray axis extending in a first direction, the first visible light emitter being configured and oriented to have a second emission ray axis relative to the first mounting structure, the second emission ray axis extending in a second direction, the first direction defining an angle of at least 50 degrees relative to the second direction.

[0169] Fig.11 An embodiment of a device 110 within the scope of this twelfth aspect is depicted. The device 110 includes a plurality of electromagnetic radiation emitters and a mounting structure 111. The plurality of electromagnetic radiation emitters include a plurality of NIR emitters 112 on a first surface 113 of the mounting structure 111 and a plurality of visible light emitters 114 on a second surface 115 of the mounting structure 111. A first 112-1 of the NIR emitters emits light having an emission ray axis 116, and a first 114-1 of the visible light emitters emits light having an emission ray axis 117. The emission ray axis 116 extends in a first direction, the emission ray axis 117 extends in a second direction, and (in this embodiment) the first direction defines a 90 degree angle relative to the second direction.

[0170] In some embodiments, the device may appropriately include or exclude any of the following: each of the multiple NIR emitters in the electromagnetic radiation emitting device has a corresponding emission ray axis, and its corresponding direction is within 10 degrees of the first direction, each of the multiple visible light emitters in the electromagnetic radiation emitting device has a corresponding emission ray axis, and its corresponding direction is within 10 degrees of the second direction, and the first direction defines an angle of at least 50 degrees relative to the second direction.

[0171] In some embodiments, the first mounting structure may include at least a first mounting structure surface and a second mounting structure surface, each of the multiple NIR emitters in the electromagnetic radiation emitting device is on the first surface of the first mounting structure, each of the multiple visible light emitters in the electromagnetic radiation emitting device is located on the second surface of the first mounting structure, and the first surface of the first mounting structure defines an angle of at least 50 degrees relative to the second surface of the first mounting structure.

[0172] In a thirteenth aspect, an apparatus comprises at least a first electromagnetic radiation emitter configured to deliver NIR to a person in a first person treatment position and at least a first person interaction element configured to prompt a user in the first person treatment position to perform a cognitive activity.

[0173] The device can provide one or a combination of effects that provide useful effects to people with AD, or to prevent AD or slow the progression of AD and other cognitive disorders. The device can also be used to treat, prevent or slow the progression of one or more of the movement disorders and / or behavioral / emotional disorders discussed herein.

[0174] In some embodiments, the cognitive activity enhanced by the treatment is selected from the group of cognitive activities consisting of (1) answering questions, (2) solving puzzles, and (3) performing movements in response to visual and / or auditory cues.

[0175] In a fourteenth aspect, the apparatus comprises at least a first mounting structure and at least a first electromagnetic radiation emitter, the first electromagnetic radiation emitter being configured to emit electromagnetic radiation comprising NIR, the first mounting structure having no area in which a first point is no more than 0.1 cm, no more than 0.2 cm, no more than 0.3 cm, no more than 0.4 cm, no more than 0.5 cm, no more than 0.7 cm, or no more than 1.0 cm from a second point, and a first line perpendicular to a first plane tangent to the first point defines an angle greater than 45 degrees, greater than 60 degrees, or greater than 75 degrees relative to a second line perpendicular to a second plane tangent to the second point.

[0176] For example, Fig.11The illustrated embodiment is an electromagnetic radiation emitting device 110 comprising a first mounting structure 111 and a plurality of electromagnetic radiation emitters 112 configured to emit electromagnetic radiation comprising NIR, and the first mounting structure 111 is sufficiently smooth to not have any such region (having sharp edges or regions) in which a first point is separated from a second point by no more than 0.1 cm, and a first line perpendicular to a first plane tangential to the first point defines an angle greater than 60 degrees relative to a second line perpendicular to a second plane tangential to the second point. For example, when moving from a first surface 113 to a second surface 115, when moving from one point to any other point within 0.1 cm, the angle defined by the plane perpendicular to the first point and the plane perpendicular to the second point does not exceed 60 degrees in any case.

[0177] By configuring the first mounting structure to be free of any of the areas discussed in any of the above options, to the extent desired, the first mounting structure does not have any sharp corners or angles (or other areas) such that if a person (e.g., a person who may be sleeping) bumps into the first mounting structure (or bumps into the first mounting structure), the likelihood of the person being cut or otherwise injured is at a desired level. Thus, the device can minimize or avoid harm to the user / patient.

[0178] In a fifteenth aspect, the apparatus comprises at least one first mounting structure; and a plurality of electromagnetic radiation emitters, the plurality of electromagnetic radiation emitters comprising at least a first group of electromagnetic radiation emitters, the first group of electromagnetic radiation emitters comprising at least 20 electromagnetic radiation emitters, each configured to emit electromagnetic radiation comprising NIR, each of the first group of electromagnetic radiation emitters having a corresponding tangent plane perpendicular to a corresponding emission ray axis of the electromagnetic radiation emitter, each of the corresponding tangent planes defining an angle of no more than 20 degrees relative to the first plane.

[0179] In a sixteenth embodiment, the device used in the method is a laptop, cell phone, television or movie screen adapted to provide light emission at a desired wavelength. In some aspects, the light is provided at one or more desired wavelengths for a predetermined period of time. When light is provided at more than one desired wavelength, the wavelengths may be emitted simultaneously or sequentially. When a user views the device, the user is exposed to the desired radiation.

[0180] In a seventeenth embodiment, the device is a shower or bathtub equipped with a light source that emits light at one or more desired wavelengths when the user is in the shower or bathtub. When light is provided at more than one desired wavelength, the wavelengths may be emitted simultaneously or sequentially. When the user views the device, the user is exposed to the desired radiation. The light source may include an actuator or timer to control how long the light is emitted.

[0181] In an eighteenth embodiment, the device is a lamp equipped with a light source that emits light at one or more desired wavelengths when a user is in a room including the lamp. Representative lamps include ceiling lights, electric lamps, etc. When light is provided at more than one desired wavelength, the wavelengths may be emitted simultaneously or sequentially. When a user views the device, the user is exposed to the desired radiation. The light source may include an actuator or timer to control how long the light is emitted.

[0182] In a nineteenth embodiment, the device is a housing in which the patient / user can sit, wherein light is provided inside the housing so that it shines on the patient / user. When light is provided at more than one desired wavelength, the wavelengths can be emitted simultaneously or sequentially. The light source can include an actuator or timer to control how long the light is emitted, and the light source can be turned on or off, for example based on when a door is first opened and then closed, based on when the patient / user sits on a chair inside the housing, etc. In this embodiment, the sensor can be a sensor that senses when a door is opened and then closed, or a sensor that senses when someone sits on a chair / couch inside the housing, and a light source is positioned in the housing to shine light on the patient / user when the patient / user sits on the chair / couch.

[0183] One type of housing is the type disclosed in U.S. Pat. No. 9,919,162, which applies light therapy to a user within the housing. In addition to light therapy, this type of housing allows one to co-apply aromatherapy, and also allows the user to ramp up, ramp down, or stabilize the light source, change the light source type, audio source type, aroma type, aroma volume, air temperature, air humidity, air ionization, air filtration, and time period in the housing.

[0184] The device can be used in a method comprising delivering NIR from a NIR emitter to a person's head, wherein the NIR has a radiance of 1 mW / cm 2 Up to 50mW / cm 2 The method of claim 1 further comprising: providing a first sensor within a range of 0.1° and sensing at least a first parameter on a first sensor. The apparatus used in these methods may include any sensor described herein. When used in conjunction with any apparatus described herein, each method described in this section may also include mounting an electromagnetic radiation emitting apparatus including one or more electromagnetic radiation emitters on, partially in, or completely in furniture (e.g., a bed, chair, mattress, pillow, etc.).

[0185] Like the device, the method is useful in a variety of ways, one of which is to provide treatment that is customized to specific characteristics of the user and / or environment, and / or to achieve special user / patient compliance, such as NIR treatment or treatment using other wavelengths of light.

[0186] In some embodiments of the methods described herein, the first parameter is selected from the group consisting of parameters of a person and parameters of an environment in an area where the person is located.

[0187] In another embodiment, the method comprises delivering NIR from at least a first, second, third, fourth, and fifth electromagnetic radiation emitter to a human head, the human head being within 100 cm of each electromagnetic radiation emitter, whereby the combined irradiance of the NIR from the first, second, third, fourth, and fifth electromagnetic radiation emitters incident on the human head is between 0.5 mW / cm 2 Up to 5mW / cm 2 In some embodiments, the method comprises delivering NIR from no more than 60 electromagnetic radiation emitters to the head of a person.

[0188] In another embodiment, the method comprises delivering NIR from a NIR emitter to a person's head and sensing at least one parameter on a sensor selected from the group consisting of an identity sensor, a human body sensor, a feature sensor, a head sensor, a head orientation sensor, a face sensor, a weight sensor, a brain wave sensor, a pulse sensor, a breathing sensor, a body temperature sensor, a blood pressure sensor, an oxygenation sensor, a skin resistance sensor, a skin temperature sensor, a motion sensor, a vibration sensor, an impact sensor, an eye state sensor, a body movement sensor, a clothing detector, an ambient temperature sensor, an ambient humidity sensor, an ambient noise sensor, and a global positioning sensor.

[0189] In some embodiments, the first sensor is an identity sensor, the electromagnetic radiation emitting device stores treatment information including the date and time of NIR treatment applied to each individual, and the NIR dose applied to each individual during the NIR treatment, the electromagnetic radiation emitting device stores regimen information including the required schedule for applying NIR treatment to each individual, the electromagnetic radiation emitting device determines the identity of the first person within the detection range of the first sensor, the electromagnetic radiation emitting device determines whether the first person needs NIR treatment based on the detected identity of the first person, the treatment information of the first person stored in the electromagnetic radiation emitting device, and the regimen information of the first person stored in the electromagnetic radiation emitting device, and if necessary, the NIR treatment that should be applied to the first person, and if the electromagnetic radiation emitting device determines that the first person needs NIR treatment based on the detected identity of the first person, the treatment information of the first person stored in the electromagnetic radiation emitting device, and the regimen information of the first person stored in the electromagnetic radiation emitting device, the required NIR treatment, the electromagnetic radiation emitting device applies the required NIR treatment to the first person.

[0190] In some embodiments, the first sensor is an identity sensor, the electromagnetic radiation emitting device determines the identity of a first person within a detection range of the first sensor based on information from the identity sensor, the electromagnetic radiation emitting device stores regimen information containing required NIR treatments to be administered to each person, the electromagnetic radiation emitting device determines whether NIR treatment should be administered to the first person based on the determined identity of the first person, and if the electromagnetic radiation emitting device determines that NIR treatment should be administered to the first person, then based on the determined identity of the first person and the stored regimen information for the first person, the electromagnetic radiation emitting device administers the required NIR treatment to the first person.

[0191] In some embodiments, the electromagnetic radiation emitting device receives an input personal identity including an input identity of a first person, the electromagnetic radiation emitting device stores treatment information including the date and time of NIR treatment administered to each individual, and the NIR dose administered during the NIR treatment, the electromagnetic radiation emitting device stores regimen information including a required agenda for NIR treatment to be administered to each individual, the electromagnetic radiation emitting device determines whether the first individual needs NIR treatment, and if so, the NIR treatment that should be administered to the first individual based on the identity of the first person, the treatment information of the first person stored in the electromagnetic radiation emitting device, and the regimen information of the first person stored in the electromagnetic radiation emitting device, and if the electromagnetic radiation emitting device determines that the first individual needs NIR treatment based on the input identity of the first person, the treatment information of the first person stored in the electromagnetic radiation emitting device, and the regimen information of the first person stored in the electromagnetic radiation emitting device, the electromagnetic radiation emitting device administers the required NIR treatment to the first individual.

[0192] In some embodiments, the electromagnetic radiation emitting device receives an input personal identity including an input identity of a first person, the electromagnetic radiation emitting device stores regimen information including the desired NIR treatment to be administered to each individual, and the electromagnetic radiation emitting device administers the desired NIR treatment to the first individual based on the input identity of the first person and the stored regimen information for the first person.

[0193] In some embodiments, the first sensor detects a first person within a detection range of the first sensor, and when the first sensor detects that the first person is within the detection range of the first sensor, the electromagnetic radiation emitting device applies NIR treatment to the first person. In some such embodiments, the first sensor is selected from a group of sensors consisting of a human body sensor, a head sensor, a head orientation sensor, a face sensor, a motion sensor, an eye state sensor, a body motion sensor, and a weight sensor.

[0194] In some embodiments, the electromagnetic radiation emitting device stores treatment information, the treatment information including the date and time of the NIR treatment that has been applied, and the NIR dose applied to each person during the NIR treatment, the electromagnetic radiation emitting device stores protocol information, the first sensor detects the first person within the detection range of the first sensor, the electromagnetic radiation emitting device determines whether the first person needs NIR treatment based on the treatment information and protocol information stored in the electromagnetic radiation emitting device, and if so, the NIR treatment that should be applied to the first person, and if the electromagnetic radiation emitting device determines that the first person needs NIR treatment based on the treatment information and protocol information stored in the electromagnetic radiation emitting device, the required NIR treatment, the electromagnetic radiation emitting device applies the required NIR treatment to the first person. In some such embodiments, the first sensor is selected from a sensor group consisting of a human body sensor, a head sensor, a head orientation sensor, a facial sensor, a motion sensor, an eye state sensor, a body motion sensor, and a weight sensor.

[0195] In another embodiment, the method involves delivering electromagnetic radiation to a person from a device configured to emit (1) visible light including at least one wavelength in the range of 490 nm to 500 nm and (2) near UV light. In some embodiments, the method further comprises sensing at least a first characteristic on a first sensor.

[0196] In another embodiment, the method comprises emitting red visible light to an individual from an apparatus comprising at least a first mounting structure, at least a first electromagnetic radiation emitter, and at least a first sensor; wherein each electromagnetic radiation emitter in the apparatus emitting red visible light is mounted on at least one of the at least first mounting structures, and wherein the corresponding emission ray axis of each electromagnetic radiation emitter emitting red visible light does not pass through any of the at least first mounting structures.

[0197] Fig.12 An embodiment of a device 120 within the scope of the fifth aspect discussed above is depicted and can be used in a method according to the twentieth aspect described herein. The device 120 includes a plurality of electromagnetic radiation emitters and a mounting structure 121. The plurality of electromagnetic radiations include a plurality of emitters 122 that emit red visible light and a plurality of light emitters 124 that emit warm white light (i.e., most of the emitted light is between about 500nm and about 700nm). The red emitters 122 are on a first surface 123 of the mounting structure 121, and the warm white emitters 124 are on a second surface 125 of the mounting structure 121. The light emitted from each respective red emitter 122 has a respective emission ray axis 126, and each respective emission ray axis 126 does not pass through any portion of the mounting structure 121.

[0198] In some embodiments, the method further comprises sensing at least a first characteristic on a first sensor. In some aspects of such embodiments, the first sensor is at least 50 mm from the person illuminated by the red visible light.

[0199] In another embodiment, the method includes actuating at least a first actuator of an electromagnetic radiation emitting device, the electromagnetic radiation emitting device including at least a first actuator and at least a first electromagnetic radiation emitter, the at least first electromagnetic radiation emitter being configured to emit electromagnetic radiation comprising red visible light, and actuating the first actuator causes the first electromagnetic radiation emitter to emit electromagnetic radiation comprising red visible light having a wavelength in the range of 600nm-640nm. In some embodiments, the first actuator is a button, and in other embodiments, it is a timer. In some embodiments, the NIR emitter is partially located in a bed, chair, pillow, or mattress, and in other embodiments, it is completely located in the bed, chair, pillow, or mattress.

[0200] In another embodiment, the method includes attaching at least a first electromagnetic radiation emitting device to a bed, chair, pillow, or mattress, the electromagnetic radiation emitting device including at least a first electromagnetic radiation emitter and at least a first attachment feature, and the first electromagnetic radiation emitter is configured to emit electromagnetic radiation including NIR.

[0201] The method may further comprise the step of irradiating the patient / user while sleeping in a bed or sitting in a chair, for example, applying the radiation close to the patient's head or a portion thereof.

[0202] In some embodiments, the first electromagnetic radiation emitting device is attached to the bed, chair, pillow or mattress by at least a first attachment feature selected from the group of attachment features consisting of a suction cup, an adhesive, a magnet, a screw hole and a bolt hole.

[0203] On the other hand, the method includes emitting light selected from NIR, IR light and UV light from an electromagnetic radiation emitting device including a plurality of electromagnetic radiation emitters, the plurality of electromagnetic radiation emitters including at least a first NIR emitter, a first NIR emitter configured to emit electromagnetic radiation including NIR, at least a first IR light emitter, the first IR light emitter configured to emit electromagnetic radiation including IR light; and at least a first UV light emitter, the first UV light emitter configured to emit electromagnetic radiation including UV light.

[0204] For example, the method can be used to provide a specific electromagnetic radiation therapy (involving different types of radiation, for example, which may include NIR and IR, NIR and UV, IR and UV, or NIR, IR and UV, and optionally also visible light, simultaneously, sequentially, or a combination of both simultaneously and sequentially) to provide a useful effect on a human.

[0205] In some embodiments, the method comprises emitting NIR, IR light and UV light simultaneously from the electromagnetic radiation emitting device, and in other embodiments, at least one of the NIR, IR light and UV light is not emitted during a portion of the time when at least another of the NIR, IR light and UV light is emitted. In some embodiments, the electromagnetic radiation emitting device further comprises at least a first visible light emitter.

[0206] According to a twenty-fifth aspect of the inventive subject matter, a method is provided, comprising positioning a first electromagnetic radiation emitter (1) on a first piece of furniture, (2) partially in the first piece of furniture, or (3) completely in the first piece of furniture, the first piece of furniture being selected from the group consisting of a pillow, a mattress, a bed, and a chair, the first electromagnetic radiation emitter being configured to emit electromagnetic radiation comprising NIR.

[0207] On the other hand, the method includes emitting light selected from NIR and visible light of at least a first color temperature from an electromagnetic radiation emitting device including a plurality of electromagnetic radiation emitters and a color temperature selection element, the plurality of electromagnetic radiation emitters including: at least a first electromagnetic radiation emitter configured to emit electromagnetic radiation including NIR; and at least a first variable color temperature emitting element including one or more variable color temperature emitting element emitters, actuating the color temperature selection element to select a first color temperature from at least two selectable color temperatures, thereby causing the electromagnetic radiation emitting device to emit visible light of the first color temperature.

[0208] The methods can provide specific electromagnetic radiation treatments (including NIR, visible light of one or more color temperatures, or a combination of NIR and visible light of one or more color temperatures, simultaneously, sequentially, or a combination of both) that provide useful effects on humans.

[0209] In some embodiments, the NIR and visible light of the first color temperature are emitted simultaneously, while in other embodiments, the visible light of the first color temperature and the visible light of the second color temperature are not emitted simultaneously.

[0210] On the other hand, the method includes emitting NIR from at least a first NIR emitter; and emitting visible light from at least a first visible light emitter, the first NIR emitter and the first visible light emitter are on a first mounting structure, the NIR has a first emission ray axis relative to the first mounting structure, the first emission ray axis extends in a first direction, the visible light has a second emission ray axis relative to the first mounting structure, the second emission ray axis extends in a second direction, and the first direction defines an angle of at least 50 degrees relative to the second direction.

[0211] In another aspect, the method includes delivering NIR to a person's head; and prompting the person to perform a cognitive activity while the person's head receives the NIR.

[0212] These methods can be performed using any of the devices described herein. The methods can provide specific NIR treatments that provide useful effects in humans, and in particular provide a combination of effects that provide useful effects in humans with AD or that provide useful effects in preventing AD or slowing the progression of AD or other cognitive disorders.

[0213] In some embodiments, the cognitive activity is selected from the group consisting of: (1) answering questions, (2) solving puzzles, and (3) performing movements in response to visual and / or auditory cues.

[0214] In another aspect, the method comprises emitting NIR from a first electromagnetic radiation emitter in an electromagnetic radiation emitting device, the electromagnetic radiation emitting device comprising at least a first mounting structure and a first electromagnetic radiation emitter, wherein the first mounting structure does not have any area in which a first point is spaced no more than 0.1 cm from a second point, and a first line perpendicular to a first plane tangent to the first point defines an angle greater than 60 degrees relative to a second line perpendicular to a second plane tangent to the second point.

[0215] In another aspect, the method includes emitting NIR from at least 20 electromagnetic radiation emitters, each electromagnetic radiation emitter having a corresponding tangent plane perpendicular to a corresponding emission ray axis of the electromagnetic radiation emitter, each of the corresponding tangent planes defining an angle of no more than 20 degrees relative to the first plane.

[0216] As described above, various embodiments according to the subject matter of the present invention involve various electromagnetic radiation emitters. In general, any suitable emitter can be used to provide the corresponding type of electromagnetic radiation, and those skilled in the art are familiar with a variety of electromagnetic radiation emitters. For example, electromagnetic radiation emitters that emit light of IR and NIR wavelengths (e.g., 700nm-1400nm) can be found at https: / / en.wikipedia.org / wiki / Infrared; electromagnetic radiation emitters that emit red light or other visible light (e.g., 380nm-780nm) can be found at https: / / en.wikipedia.org / wiki / Visible_spec trum; other wavelengths of light can also be used, such as a mixture of light wavelengths or light wavelengths used alone, such as NIR for AD, NIR / red for sleep aids, red or amber for night lights, white light for reading, bright blue / white light for wakefulness and / or alertness, and blue or UVA for bacteria / fungus control.

[0217] Representative examples of types of electromagnetic radiation emitters include light emitting diodes (LEDs), laser diodes, incandescent lamps, fluorescent lamps, luminescent materials (up-converting or down-converting, pumped with any suitable light source), thin film electroluminescent devices, light emitting polymers (LEPs), halogen lamps, high intensity discharge lamps, electroluminescent lamps, etc., with or without filters. Electromagnetic radiation emitters can generally be used alone, with other similar electromagnetic radiation, and / or with different types of electromagnetic radiation (i.e., in some cases, there is a combination of one or more light sources of each of multiple types).

[0218] Representative examples of specific features that may be employed in the methods and devices described herein include: electromagnetic radiation emitters are products based on modulated NIR or red LEDs that illuminate / radiate and penetrate the human body; combining light therapy with feedback sensing; using lightweight materials; hot and cold structures; low voltage power supply; using red LEDs (630nm, 660nm), NIR LEDs (810nm, 830nm, 870nm); using light modulation (10Hz pulses and / or pulse shaping); using sensor feedback (ultrasonic Doppler, skin resistance, pulse, pulse velocity, camera, skin temperature); using links to wearable technology, such as fitbit, apple watch, etc., for sensor feedback or other purposes; combining light therapy with magnetic therapy, sound therapy, ultrasound therapy, heat therapy, massage therapy; using the devices and methods disclosed herein for cosmetic treatments and / or interventions (e.g., red light for hair, yellow light for skin, blue light for fungi).

[0219] In some aspects, the device detects the presence of a living being and activates a treatment or therapy. In some aspects, the device recognizes the presence of a "head" and activates a treatment or therapy based on that (and in some cases, recognizes the location and / or orientation of the head and customizes the treatment or therapy based on the location and / or orientation of the head). In some aspects, the device measures biological data (e.g., surface temperature, oxygenation, pulse rate, pulse before, during, and / or after a treatment or therapy), and in some cases customizes a treatment or therapy (or the next treatment or therapy) based on such data. In some aspects, the device detects whose head is in the treatment area (i.e., the identity of the individual), and in some cases personalizes data storage and / or treatment / therapy.

[0220] In very specific aspects, humans are treated with NIR having parameters selected based on the criteria described in this paragraph: wavelength (e.g., 810 nm) based on (1) effectiveness of light penetration into living tissue due to minimal absorption by the three major tissue components, i.e., chromophores, hemoglobin and melanin, and water, and based on (2) effectiveness of mitochondrial absorption, which is believed to be responsible for the biological effects of photobiomodulation; energy density (e.g., 60 J / cm 2), referring to data demonstrating transcranial laser therapy for human stroke and knowledge of the optical properties of human tissue; power density (e.g., 250 mW / cm 2 ) to ensure safety and avoid skin heating.

[0221] In some aspects of these embodiments, since the light source is relatively far from the user, it may be advantageous to use a higher power light source compared to a device that is in direct contact with or very close to the user. U.S. Publication No. 20150112411 discloses a device with a high-power LED that can be used in conjunction with the treatment described herein. The device is a portable high-power light emitting diode photobiological device that includes a plurality of light emitting diodes, including a first light emitting diode having a first predetermined wavelength and a first emission axis, and a second light emitting diode having a second predetermined wavelength and a second emission axis. The device may further include a plurality of optical devices, including a first optical device corresponding to a first one of the plurality of light emitting diodes, which defines a first dispersion pattern of enhanced light intensity centered on the first emission axis, and a second optical device corresponding to a second one of the plurality of light emitting diodes, which defines a second dispersion pattern of enhanced light intensity centered on the second emission axis.

[0222] The device may further include an optical face defined by a flat plane. A first of the plurality of light emitting diodes may be positioned at a first oblique angle relationship relative to the flat plane of the optical face. A second of the plurality of light emitting devices may also include a "user control area" that provides indicators and switches by which a user may select and confirm desired treatment parameters. The device may also include a housing that substantially encloses and retains the light emitting diodes, the optical device, and the user control area. The device may also optionally include an optical face that is substantially integrated with the housing to provide a smooth surface toward the treatment area, and / or an optical face that includes a diffuser for evenly dispersing light.

[0223] These devices can be used farther away from the user than LED light therapy devices that come in contact with the user. While conventional light therapy devices may lose more than 50% of their emitted power at distances as small as 1 / 2", these high power LEDs with reflective optics with approximately 45-90 degree dispersion angles can deliver the desired light output with uniform intensity dispersed across a large area in either contact or non-contact treatment methods.

[0224] These devices can eliminate the need for direct contact by using reflector optics and high-power LEDs with a predetermined frequency output. Contactless treatment further addresses treating sensitive, painful, or hard-to-reach body parts. In turn, by incorporating the emitting surface of the optics into the surface of the housing, some embodiments of the device can be configured to be quickly and easily cleaned and disinfected between uses.

[0225] The device may include a sealed light emitting surface that can be cleaned and sterilized before use. The device may also include optics associated with the LEDs for controlling the spread and intensity of the emitted light over a larger area to increase the therapeutic effect. The device may also provide a combination of predetermined light frequencies for use over a range of treatment durations.

[0226] In another embodiment, a housing similar to a tanning bed is used, but with a light source that emits light at wavelengths, power levels, etc. as described herein. Such tanning beds are commercially available, and the light source can be modified to provide light at the wavelengths described herein. Tanning beds typically include a timer and / or actuator that controls the time period for which the light is applied.

[0227] The specific devices described above are discussed in more detail below. Various embodiments of the devices described herein are shown in Figure 1-10 Each of these devices can be configured to emit NIR light, or alternatively, can be configured to emit a combination of multiple wavelengths, which may or may not include NIR light. For example, light can be applied at a first anti-inflammatory wavelength, a second wavelength that promotes the production and / or release of endogenous nitric oxide, a wavelength that promotes the production and / or release of endogenous neurotransmitters, and / or a wavelength that repairs the blood-brain barrier. In some embodiments of each of these devices, light is emitted in a combination of multiple wavelengths, the combination including at least a first anti-inflammatory wavelength and a second wavelength that promotes the production and / or release of endogenous nitric oxide. These wavelengths can be emitted simultaneously or sequentially according to a predetermined emission schedule, or can be emitted with overlapping emission schedules. These wavelengths can also be emitted directly and / or indirectly to all or one or more parts of the brain. Depending on the indication to be treated or prevented, it may be necessary to expose a portion of the brain to one wavelength or wavelength range, and another portion of the brain to another wavelength or wavelength range.

[0228] Figure 1The front of an embodiment of an electromagnetic radiation emitting device as described herein is schematically depicted. The device includes a plurality of emitters 30, a human body sensor 10, and a light sensor 20 arranged in an array. The array of emitters 30 defines a pattern having a 30 mm border, four rows, and 12 columns around its perimeter. The spacing between each row and its adjacent row (or multiple adjacent rows) is 25 mm. The spacing between each column and its adjacent column (or multiple adjacent columns) is 25 mm. Each emitter 30 can be configured to emit light of any wavelength (or within a wavelength range), for example, in some embodiments, each emitter 30 is configured to emit NIR light. The human body sensor 10 is configured to detect whether a person is within the detection range of the device. The light sensor can be any desired light sensor, for example, a sensor that detects whether light of a specific wavelength (or light within a specific wavelength range) is incident on the device, a sensor that detects the radiance of light incident on the device, the radiance of light of a specific wavelength or wavelength range incident on the device, etc.

[0229] Figure 2 is similar to Figure 1 A cross-sectional view of an electromagnetic radiation emitting device of the device depicted in FIG. 1 , along a line similar to Figure 1 The cross section is taken along line II-II. Figure 2 A plurality of emitters 40 are shown attached to a printed circuit board 50. Each emitter 40 can be configured to emit light of any wavelength (or within a range of wavelengths, or at a combination of wavelengths). In some embodiments, each emitter 40 is configured to emit NIR light, and in other embodiments, the emitters are configured to emit a combination of wavelengths, wherein the light is administered at a first anti-inflammatory wavelength and a wavelength that promotes the production and / or release of endogenous nitric oxide. Figure 2 As shown, each emitter 40 is located on the surface of the device (i.e., along the right edge of the device, at Figure 2 direction shown).

[0230] Figure 3 Schematically depicting an embodiment of an electromagnetic radiation emitting device as described herein, attached to a chair, and a patient sitting in the chair. The device is configured to deliver light of a desired wavelength (or range and / or combination of wavelengths) to each of one or more regions of the patient's body. For example, in some embodiments, the device is configured to deliver NIR light to the patient's head, while in other embodiments, it is configured to deliver a combination of wavelengths, wherein the light is administered at a first anti-inflammatory wavelength and a second wavelength that promotes the production and / or release of endogenous nitric oxide.

[0231] Figure 4Schematically depicted are embodiments of an electromagnetic radiation emitting device as described herein, and a head of a person positioned proximate thereto. The device is configured to deliver light of a desired wavelength (or range and / or combination of wavelengths) to each of one or more regions of the patient's head. For example, in some embodiments, the device is configured to deliver NIR light to the patient's head, while in other embodiments, is configured to emit a combination of wavelengths, wherein the light is administered at a first anti-inflammatory wavelength and a second wavelength that promotes the production and / or release of endogenous nitric oxide.

[0232] Figure 5 Schematically depicts an embodiment of an electromagnetic radiation emitting device 30 as described herein, attached to a bed with a patient in bed. The device is configured to deliver light of a desired wavelength (or wavelength range) to each of one or more regions of the patient's head. For example, in some embodiments, the device is configured to deliver NIR light to the patient's head, while in other embodiments, the emitter is configured to emit a combination of wavelengths, wherein the light is administered at a first anti-inflammatory wavelength and a second wavelength that promotes the production and / or release of endogenous nitric oxide.

[0233] Figure 6 A circuit for an embodiment of an electromagnetic radiation emitting device as described herein is schematically depicted (as a block diagram). The circuit comprises a CPU and a memory 100. The CPU sends and receives signals via serial communication (e.g., WiFi or ). The CPU receives signals from GPS 90. The CPU receives signals from microphone 60. The CPU sends signals to speaker 70. The CPU is configured to drive the NIR LED as well as other LEDs (e.g., visible light). The CPU receives signals from a temperature sensor. The CPU is also connected to a PTR diode. A power supply 110 provides power to the LEDs and circuits from a battery and / or a wall socket.

[0234] Figure 7 Schematically depicted (as a block diagram) is additional circuitry for an embodiment of an electromagnetic radiation emitting device as described herein. The circuitry includes a controller CPU 140. The CPU 140 sends signals to and receives signals from the memory 130. The CPU 140 also sends signals to and receives signals from the timer 120. The CPU 140 receives signals from the GPS 90. The CPU also receives signals from the GPS 90 via WiFi and / or The circuit also includes a power connector and a battery to provide current to the CPU 140 and the NIR LED, the red LED, and the white LED based on the signal provided by the CPU 140.

[0235] Figure 8 The front of another embodiment of the electromagnetic radiation emitting device as described herein is schematically depicted. The device includes a plurality of emitters 30 arranged in an array, a plurality of ambient light LEDs (along the top side of the device), a microphone 60, a camera 170, and a proximity detector 180. The front can be facing the patient's head. Each emitter 30 can be configured to emit light of any wavelength (or within a range of wavelengths, or a combination of wavelengths). In some embodiments, each emitter 30 is configured to emit NIR light, and in other embodiments, the emitters are configured to emit a combination of wavelengths, wherein light is applied at a first anti-inflammatory wavelength and a second wavelength that promotes the production and / or release of endogenous nitric oxide. In some embodiments, the proximity detector 180 controls when and how long the device operates by detecting the presence of a person and / or detecting motion).

[0236] Fig. 9 is a perspective schematic diagram of another embodiment of an electromagnetic radiation emitting device as described herein. The device includes a plurality of emitters 30 arranged in an array, a plurality of ceiling / wallwash emitters 200 (along the top side of the device), an ambient light detector 210, a microphone 60, a speaker 70, and a sensor 190. The device is secured in place by a bracket 220. Each emitter 30 can be configured to emit light of any wavelength (or within a range of wavelengths, or a combination of wavelengths). In some embodiments, each emitter 30 is configured to emit NIR light, and in other embodiments, the emitters are configured to emit a combination of wavelengths, wherein the light is administered at a first anti-inflammatory wavelength and a second wavelength that promotes the production and / or release of endogenous nitric oxide.

[0237] Fig.10 Schematically depicts an embodiment of an electromagnetic radiation emitting device as described herein, wherein a person's head is close to the electromagnetic radiation emitting device. Fig.10 , the device includes a plurality of emitters 30, a sensor 190 and a ceiling light emitter (on the top surface of the device). The device is fixed in place by attachment to a bracket 220, and the height of the device can be adjusted (relative to the patient's head 240).

[0238] II. Devices that come into direct contact with the user

[0239] In addition to devices that do not come into contact with the user, devices that do come into contact with the user may also be used.The light may be administered in any manner that allows the light to pass through the skin and into the brain.

[0240] Each device includes or may include common components. These include one or more light sources, a power source (which may include a rechargeable battery), a controller for controlling the light source, a switch and / or actuator for turning the device on or off, and optional sensors, as described elsewhere herein. Since these devices come into contact with the user, a proximity sensor may be used to determine how close the light is to the patient's skin. A temperature sensor may determine the degree to which the light heats the skin. These devices may also include a device for removing heat from the user's skin, such as a fan or a radiator. These devices may also include a diffuser to diffuse the light so that it is more evenly distributed, or a light shield to prevent the light from shining on certain parts of the user's skin.

[0241] The device may also include an alarm for reminding the individual when it is time to start or stop treatment, a safety or shutoff mechanism for shutting off power, and / or a timing device for measuring the length of a treatment session.

[0242] In various embodiments, the device can deliver light by intracranial administration, delivery through the scalp (e.g., by using a therapeutic helmet), delivery to the eyes (e.g., by using glasses that shine light through the eyelids, or by shining light onto a screen), intranasal delivery (e.g., by a light source inserted into the nostril), delivery to the ear, delivery to a site remote from the brain (e.g., through skin overlying a bone), delivery to the blood, delivery to the skin, delivery to a body cavity (e.g., the throat), a "wearable" device for illuminating the skin, a probe designed to penetrate the skin and deliver light subcutaneously, a biocompatible implant implanted beneath the scalp, a transcutaneous irradiation module, and combinations thereof. These various devices are discussed in more detail below.

[0243] Many of these types of devices are known in the art, but are not used to administer light in the wavelength combinations as described herein, or to treat the various disorders described herein.

[0244] In one embodiment, light is delivered directly to the user's skull. U.S. Publication No. 20160235983 discloses a device for delivering light to the skull. The device includes a light source that can be positioned near the surface of the user's skull and can optionally include multiple energy ports that communicate with any of a variety of suitable light energy sources. The multiple energy ports are capable of emitting light energy directed toward the subject's skull.

[0245] The device also includes a controller to control the light emission at a predetermined energy level for a predetermined time period. The controller includes a processor and digital data storage, and a biometric measurement device capable of quantifying one or more biological aspects of the user. The biometric measurement device can continuously or intermittently provide digital data to the controller, which indicates one or more measurements that quantify the biological aspects of the user before, during and / or after the administration of the predetermined light therapy.

[0246] The apparatus may include a neurofeedback system in logical communication with the controller, including external stimulation applied to the mammalian subject in the form of at least one of visual stimulation, audio stimulation, transcranial electrical stimulation, transcranial magnetic stimulation, transcranial magnetic stimulation, translingual electrical stimulation, and transcutaneous electrical stimulation. The biofeedback system may be in logical communication with the light source to continue or modify at least one of a predetermined light therapy and neurofeedback applied to the user based on one or more measurements quantifying a biological aspect of the user.

[0247] The device may also include a data storage device for storing one or more biometric measurements before, during, and / or after light therapy and / or neurofeedback therapy. The device may also include an electrical logic signal source in logical communication with the controller. These signals may cause the controller to receive input from the biometric measurement device and cause the light source to continue to deliver the predetermined light energy therapy, or selectively modify the predetermined light therapy for the user based on the input from the biometric measurement device. Modifications to the predetermined light therapy may include modifying the selection of the light inlet and the wavelength, energy level, duration, and / or frequency of the emitted light.

[0248] In one embodiment, light is administered using an intracranial light emitting implant, such as the implant disclosed in US Pat. No. 8,821,559, but equipped with a light source emitting one or more wavelengths other than those disclosed in the '559 patent and / or used to treat CNS disorders other than those taught in the '559 patent.

[0249] The implant includes a light source, an antenna electrically connected to the light source, and an optional but preferred controller. In use, the surgeon implants the device into the patient's brain. In order to protect the active components of the device from the influence of cerebrospinal fluid (CSF) and / or minimize foreign body reaction, in some embodiments, the light source is encapsulated in a housing. The housing is ideally made of a material transparent to the emitted wavelength. Representative housing materials include ceramics and polymers. Suitable ceramics include alumina, silicon dioxide, CaF, titanium dioxide and single crystal sapphire, and suitable polymers include polypropylene and polyester.

[0250] In some embodiments, the light emitting portion of the implant is placed separately from the LED. This can be accomplished using an optical communication device, such as an optical cable, a waveguide, a hollow tube, a fluid-filled tube, or a light pipe.

[0251] Light can also be applied using a probe. In some embodiments, the probe is inserted into the brain. In one embodiment, the probe includes a probe body configured to penetrate biological tissue, and a plurality of light sources disposed in the probe body, the plurality of light sources being high-efficiency LEDs. The light intensity is sufficient to trigger a photosensitive reaction in adjacent tissues, but is insufficient to provide a combined heat that would cause a destructive temperature rise in adjacent tissues. For example, an exemplary probe is disclosed in U.S. Publication No. 20190232083.

[0252] In other embodiments, the probe is used to introduce light into the throat so that it penetrates into specific areas of the brain and spine, which are more accessible in this way than by applying light to the scalp. For example, PCT WO 2019165302 discloses systems and methods for applying light therapy to the throat and ultimately the pharynx using a transpharyngeal probe.

[0253] The device includes a hollow structure having at least a first open end. The hollow structure includes a rotatable member, one or more coherent light generators, and for each coherent light generator, one or more lenses or reflectors are optically connected to the coherent light generator and configured to change at least one aspect of the coherent light beam. The device further includes a processing circuit, which includes a processor and a memory storing instructions. The instructions, when executed by the processor, cause the processor to accept input from an operator and generate one or more coherent light beams according to a plurality of settings configured to produce a therapeutic effect at a target treatment site. In addition, the rotatable member is configured to rotate to direct the one or more coherent light beams to the target treatment site.

[0254] In some embodiments, light is administered so that it is directed backward and upward, or directed toward the pharynx or posterior portion of the pharynx, and toward the upper brainstem, midbrainstem, lower brainstem, and upper spine. Delivering light therapy to the sleep centers of the brainstem or to a brainstem that has sustained a contusion or concussion via a transpharyngeal probe may be a better method of delivering light to these tissues than delivering light therapy transcranially or topically through the forehead skin and frontal skull region.

[0255] Light can also be applied using a catheter. For example, U.S. Publication No. 20100121420 discloses the use of a catheter to provide phototherapy to a brain region. The catheter can include any combination of LEDs, OLEDs, lasers or other light emitting devices on the tip, alone or in array form, or any other form of light through an optical fiber catheter. Light can be introduced into the vascular system by direct percutaneous or intraoperative penetration, or by entering a cavity, such as a nasal passage, mouth and ear, or a region or cavity filled with fluid. People can use catheters and / or optical fiber catheters of various sizes to deliver light to the brain region in one or more blood supply branches by entering smaller blood vessels along larger blood vessels (arteries or veins or any other type of blood vessels). This allows the use of a combination of catheters and / or optical fiber catheters of various sizes to generate and surround light around a given brain region and / or a watershed region for entering the blood vessels in the region. Arteries and / or veins can be used for entry. Alternatively, the phototherapy described herein can be applied to the region of the subdural or epidural position and the blood supply in these regions by entering the central sulcus through the skull or entering the ventricular system through the skull.

[0256] In some embodiments, light is applied using an implant located between the skull and the scalp. PCT WO2012024243 discloses a minimally invasive device that can be used to treat neurological disorders by low-level light therapy using the wavelengths described herein. The device includes a substantially flat, biocompatible substrate configured to be implanted between the scalp of a subject and the skull of a subject, and configured to be anchored to the outer surface of the skull of the subject, and one or more light sources are mechanically coupled to the substrate.

[0257] In other embodiments, light is delivered directly to the scalp, for example using a light-emitting helmet. Many laser and LED helmets are commercially available and can be used to treat hair loss, and they can be modified to treat central nervous system disorders by providing light of the wavelengths or wavelength combinations described herein. A representative light-emitting helmet is disclosed in U.S. Publication No. 20170028216. A common feature of these helmets is that they include multiple light sources, whether laser or LED light sources, on or near the surface of the helmet that contacts the user's scalp. The controller can control the length of time the light is applied, the intensity of the light applied, and, if necessary, which desired locations of the scalp the light is applied to.

[0258] Another suitable device for applying light to the scalp is disclosed in U.S. Pat. No. 10,188,872. The device can illuminate at least a portion of a patient's brain with light and includes a light source, an output optical element including a rigid and substantially thermally conductive material, and a surface configured to be in thermal communication with the patient's body. The second surface can be configured to face away from the patient's scalp during treatment. The device can include a cooler thermally coupled to the second surface of the output optical element to remove heat from the output optical element through the second surface; and a heat sink thermally coupled to the cooler. The heat sink can be positioned so that light propagates through the heat sink and through the output optical element.

[0259] U.S. Publication No. 20120046716 discloses a customized transcranial light therapy device that follows the contours of a patient's head. The device includes a ring assembly and a light module located between an upper ring and a lower ring of the ring assembly. A first generally circular ring and a second generally circular ring having a diameter smaller than the first ring are used. The size and shape of each ring are adjusted to roughly correspond to the circumference of an individual's head. When in use, the ring is placed on the individual's head, and each ring is provided with a plurality of engagement means, such as complementary interlocking male and female protrusions, and a receiving unit for receiving and fixing a plurality of light modules. The light, which may be an LED, OLED, laser or other light source, may be pulsed, or provided in the form of a continuous wave.

[0260] The device may further include one or more light modules directed toward the skull base, eye region, or occipital region, EEG electrodes and associated monitoring mechanisms, shoulder supports, and additional securing mechanisms for securing the device around an individual's head. The device may include a transducer capable of measuring intracranial oxygenation.

[0261] Light can also target the basal ganglia. U.S. Publication No. 20150360049 discloses a system comprising a light delivery element configured to direct radiation to at least a portion of a target tissue structure, a light source configured to provide light to the light transmission element, and a controller. The target tissue structure is a portion of the patient's basal ganglia. The controller can be configured to automatically operate to irradiate the target tissue structure with radiation of the wavelength, power level, etc. described herein. The device can also include a power supply connected to a microcontroller unit (MCU), as well as an LED driver, a fan driver, and / or a temperature sensor, each of which is connected to the power supply as needed.

[0262] US Publication No. 20150360049 also discloses modifying tissue to include a light-sensitive protein and exposing the tissue expressing the light-sensitive protein to radiation. The light-sensitive protein can be an opsin, such as a depolarizing opsin, a hyperpolarizing opsin, a stimulatory opsin, an inhibitory opsin, a chimeric opsin, or a step-function opsin. Representative opsins are selected from the group consisting of: NpHR, eNpHR 1.0, eNpHR 2.0, eNpHR 3.0, SwiChR, SwiChR 2.0, SwiChR 3.0, Mac, Mac 3.0, Arch, ArchT, Arch3.0, ArchT 3.0, iChR, ChR2, C1V1-T, C1V1-TT, Chronos, Chrimson, ChrimsonR, CatCh, VChR1-SFO, ChR2-SFO, ChR2-SSFO, ChEF, ChIEF, Jaws, ChloC, slow ChloC, iC1C2, iC1C2 2.0, and iC1C2 3.0.

[0263] Rather than targeting light specifically at one location, the user can be widely exposed to light. U.S. Publication No. 20160129279 discloses a wearable device for irradiating the skin that can be modified to emit light of the wavelengths described herein. The device can emit light at different frequencies as needed. The device includes a light source, a light diffuser optically coupled to the light source, a controller electrically coupled to the light source and configured to control the intensity and duration of the emitted light, a proximity sensor for detecting the proximity of the light diffuser to the skin, wherein the proximity sensor is electrically coupled to the controller, and a power source. The controller can be further configured to turn on the light source and keep it on during treatment.

[0264] US Publication No. 20180169434 discloses a device for applying light energy externally to a patient's head. The light is applied near a brain region where malfunction or the source of the disease to be treated occurs. The therapeutic effect can be enhanced by activating cranial nerves while applying the light.

[0265] Light can be applied directly to the face, such as by using a light mask. Light masks are commercially available that emit LED or laser light to the face at wavelengths that can treat wrinkles, acne, or other skin conditions. These masks can be modified to emit light at one or more wavelengths described herein. As with the helmet, a controller can control how long the light is applied, the intensity of the light applied, and, if desired, which desired locations on the scalp the light is applied to.

[0266] Instead of delivering light to the skull or face, light can be delivered to the bone marrow. This results in stimulated mesenchymal stem cell formation and entry into the brain, where they can have a beneficial effect on many central nervous system disorders. The energy can be incoherent and / or coherent light and can be administered percutaneously, subcutaneously, or via an intramedullary probe. A suitable device is disclosed in U.S. Patent No. 9,403,030.

[0267] In some embodiments, light is administered through the ear. A device for delivering light through the ear is described in U.S. Patent No. 10,471,276. The device is disclosed as using lasers, but can be modified to use other forms of light, such as LED light, and deliver the light to the outer ear. The device can allow for various variables, including wavelength, power, illumination area, stimulation area, distance to the skin surface, angle relative to the skin surface, and frequency and duration of stimulation.

[0268] The device of the '276 patent includes a housing adapted to be positioned over at least one target point, and at least one light source positioned on the housing, whereby light from the light source can be focused onto the at least one target point. The device includes at least one sensor in sensory communication with a subject. The sensor is adapted to sense at least one physiological or neural state of the subject and can be adapted to output at least one physiological or neural state. The device also includes a driver operably connected to the at least one light source, capable of powering and controlling the at least one light source. In addition, the device includes a command module operably connected to the driver and operably connected to the sensor. The command module can control at least one performance variable of the at least one light source, such as wavelength, power, power density, voltage, current, pulse mode, pulse frequency, beam spot diameter, angle of incidence, and combinations thereof. The controller can also receive at least one state output from the sensor, adjust at least one performance variable of the at least one light source, and evaluate any changes in the state output. If the state output is not optimized, it can adjust one or more performance variables.

[0269] In some embodiments, it is desirable to introduce the light into a body cavity, such as the nose or mouth, so that the light enters the brain. U.S. Publication No. 20100121420 discloses providing ultraviolet light to at least one of the following: (a) under the skin of a mammal; (b) to a body cavity, lumen, organ, tissue, or tissue within a body cavity of a mammal; (c) in the blood of a mammal or to the blood or to a specific type of cell; to provide a phototherapy effect thereto. The device can be modified to emit light of the wavelengths described herein and used in the methods described herein.

[0270] Light can further be administered through the nose. Fiber optic cables or waveguides can be used to reach deep into the nasal cavity, or an LED or other light source can be introduced into the nasal cavity. Light can be provided at one or more wavelengths.

[0271] Combinations of these methods may be used to provide light to multiple parts of a user in more than one manner. For example, PCT WO2019053625 discloses a photobiomodulation (PBM) system and method that directs therapeutic light energy into the brain from a combination of transcranial (through the skull) and intranasal (through the nasal passages) locations.

[0272] Transcranial administration directs light energy to the dorsal / superior region of the neocortical region of the brain, and intranasal administration directs light energy to the ventral or inferior side of the brain, providing more comprehensive coverage than current transcranial approaches alone and current intranasal approaches alone.

[0273] Light energy can be directed to one or more specific areas of the brain, including the ventral medial prefrontal cortex (vmPFC), the dorsomedial prefrontal cortex (dmPFC), the posterior cingulate cortex (PCC), the precuneus (PCu), the lateral parietal cortex (LPC), the entorhinal cortex (EC), the right dorsolateral prefrontal cortex (DLPC), the left dorsolateral prefrontal cortex (DLPC), the cerebellum, and the brainstem. In addition, when applied to the nasal cavity, light energy is directed to the ventral prefrontal cortex, the entorhinal cortex, and / or the parahippocampal region.

[0274] Light may also be applied to the external auditory canal, and may also be applied transcranially through one or more of the following skull bones: the temporal bone, the temporal prominence, the mastoid portion of the temporal bone, the petrous portion of the temporal bone, the tympanic portion of the temporal bone, the zygomatic bone, the sphenoid bone, the frontal bone, and the parietal bone.

[0275] In some embodiments, it is desirable to introduce light into the eye. By using glasses equipped with a light source that can be directed at the upper eyelid, light can be applied through the eyelid without damaging the eye or interfering with the patient's vision.

[0276] IV. Wavelengths that increase angiogenesis, provide anti-inflammatory and / or antimicrobial effects, and promote NO stimulation and / or release

[0277] The term "phototherapy" relates to the therapeutic use of light. The term "phototherapy" relates to the therapeutic use of light. As used herein, phototherapy is used to treat or prevent, lessen the severity of, or slow the progression of a central nervous system disorder.

[0278] Light therapy is used to treat or prevent microbial infections in brain tissue, including viral, bacterial, and fungal infections. The antimicrobial mechanisms of light may vary. In some embodiments, light is applied at UVA (320–400 nm), UVB (280–320 nm), and / or UVC (200–280 nm) wavelengths. Of these, UVC (wavelength 200-280 nm) is believed to be the most bactericidal.

[0279] UVC is absorbed by RNA and DNA bases in microorganisms and can cause the photochemical fusion of two adjacent pyrimidines into a covalently linked dimer, which then becomes an unpaired base (Perdiz et al., J. Biol. Chem., 275 (2000), pp. 26732-26742). UVB can also induce pyrimidine dimers, but its efficiency is not as good as UVC (id). UVA is weakly absorbed by DNA and RNA, and its effectiveness in inducing pyrimidine dimers is far less than that of UVC and UVB, but it is believed to cause additional genetic damage by producing reactive oxygen species, resulting in base oxidation and chain breakage (Tyrrell et al., J. Photochem. Photobiol. B, 63 (2001), pp. 88-102).

[0280] It is also known that nitric oxide has antimicrobial effects, and increasing the level of nitric oxide in the brain can be used to inhibit microbial infections in the brain. The exact mechanism by which nitric oxide (NO) kills or inhibits the replication of multiple intracellular pathogens is not fully understood. However, it seems to be targeted cysteine ​​proteases (Saura et al., Immunity, Volume 10, Phase 1, January 1, 1999, Pages 21-28). NO S-nitrosylates the cysteine ​​residues in the active sites of certain viral proteases, inhibiting protease activity and interrupting the viral life cycle. Since cysteine ​​proteases are essential for the virulence or replication of many viruses, bacteria, and parasites, the generation and release of NO can be used to treat microbial infections. Therefore, in some embodiments, light is applied at a wavelength that effectively enhances the generation and / or release of endogenous NO. These wavelengths are discussed in more detail below.

[0281] Light-induced release of endogenous nitric oxide ("NO") stores effectively regenerates "gaseous" (or unbound) nitric oxide, which is auto-oxidized to nitrosated intermediates and covalently bound in the body in a "bound" state. By stimulating the release of nitric oxide from endogenous stores, nitric oxide can be retained in the gaseous state for an extended duration and / or the spatial region of nitric oxide release can be expanded.

[0282] Nitric oxide is stored endogenously in various nitrosated biochemical structures. Upon receiving the required excitation energy, both nitroso and nitrosyl compounds undergo lytic cleavage of the SN, NN or MN bonds to produce free radical nitric oxide. Nitrosothiols and nitrosamines are photoactive and can be triggered to release nitric oxide by wavelength-specific excitation light.

[0283] The effects of certain wavelengths of light on the production and / or release of nitric oxide are described in U.S. Patent No. 10,525,275, the contents of which are incorporated herein by reference.

[0284] It is reported that NO can diffuse up to a distance of about 500 microns in mammalian tissue. In certain embodiments, photons of a first energy hυ1 can be supplied to tissue to stimulate enzymatic production of NO, thereby increasing endogenous storage of NO in the first diffusion zone 1. Photons of a second energy hυ2 can be supplied to tissue in an area within or overlapping the first diffusion zone 1 to trigger the release of NO from endogenous storage, thereby creating a second diffusion zone 2. Alternatively or additionally, photons of a second energy hυ2 can be supplied to stimulate enzymatic production of NO, thereby increasing endogenous storage of NO in the second diffusion zone 2. Photons of a third energy hυ3 can be supplied to tissue in an area within or overlapping the second diffusion zone 2 to trigger the release of endogenous storage, thereby creating a third diffusion zone 3. Alternatively or additionally, photons of a third energy hυ3 can be supplied to stimulate enzymatic production of NO, thereby increasing endogenous storage of NO in the third diffusion zone 3. In certain embodiments, the first, second, and third diffusion zones 1-3 may have different average depths relative to the outer epidermal surface. In certain embodiments, the first photon energy hυ1, the second photon energy hυ2, and the third photon energy hυ3 can be provided at different peak wavelengths, where the different peak wavelengths can penetrate mammalian skin to different depths - because longer wavelengths generally provide greater penetration depths. In certain embodiments, the sequential or simultaneous impact of increasing wavelengths of light can be used to "push" the nitric oxide diffusion zone deeper into mammalian tissue than would be possible by using a single (e.g., long) wavelength of light.

[0285] In addition to the effects of increased NO production and / or release on angiogenesis, blue light can also modulate microglial gene expression in the absence of optogenetic protein expression. For example, blue light with a wavelength of approximately 450 nm, delivered repeatedly in both prolonged boluses and rapid optogenetic bursts, can alter basal expression of inflammatory and neurotrophic genes in a gene-specific manner. The largest increases were seen in COX-2 and VEGF-1 expression. To this end, blue light can simultaneously express genes associated with brain tissue revascularization.

[0286] Light having a first peak wavelength and a first radiant flux that stimulates enzymatic production of nitric oxide to increase endogenous nitric oxide storage may be referred to herein as "endogenous storage increasing light" or "ES increasing light". Light having a first peak wavelength and a first radiant flux for releasing nitric oxide from endogenous storage may be referred to herein as "endogenous storage releasing light" or "ES releasing light". Light having an anti-inflammatory effect may be referred to herein as anti-inflammatory light.

[0287] In certain embodiments, two or three peak wavelengths of light are used, including one peak wavelength to provide an anti-inflammatory effect, in combination with a peak wavelength of ES-releasing light and / or a peak wavelength of ES-enhancing light. In other embodiments, one or more wavelengths of light in the UVA, UVB, or UVC range may be used instead of or in addition to ES-enhancing light or ES-releasing light.

[0288] In other embodiments, light is applied at a wavelength that reduces inflammation. As discussed above, inflammation is associated with many central nervous system disorders, and therefore inhibiting inflammation can treat, prevent, or slow the progression of central nervous system disorders associated with inflammation. Anti-inflammatory wavelengths include, for example, wavelengths between about 640nm and about 680nm. A wavelength of 850nm has an anti-inflammatory effect by reducing inflammatory cytokines and releases NO.

[0289] Furthermore, blue light can reduce the expression of pro-inflammatory genes in microglia, a type of glial cell that is found throughout the brain and spinal cord, and thus, blue light may mitigate the cytokine storm associated with various neuroinflammatory disorders, such as traumatic brain injury and microbial brain infections.

[0290] Photobiomodulation (PBM) at wavelengths of about 660 nm and about 780 nm can also have an effect on M1 inflammatory markers, such as by reducing mRNA expression and secretion of TNF-α, iNOS, and IL-1β by microglia and astrocytes, with stronger effects generally observed when using light at about 780 nm relative to light at 660 nm. PBM can also significantly reduce the expression and phosphorylation of NF-κBp65 and inhibit the generation of reactive oxygen species. This reduction in inflammatory cytokine expression and secretion can be observed using light of other wavelengths, but the greatest effect is observed using blue light, which allows for regulation of inflammation in the brain through gene expression.

[0291] In certain embodiments, each of the anti-inflammatory light, ES-enhancing light, and / or ES-releasing light and / or UVA / UVB / UVC light has a radiant flux of at least 5 mW / cm 2 , or at least 10mW / cm 2 , or at least 15mW / cm 2 , or at least 20mW / cm2 , or at least 30mW / cm 2 , or at least 40mW / cm 2 , or at least 50mW / cm 2 range, or within 5mW / cm 2 Up to 60mW / cm 2 In the range of 5mW / cm 2 Up to 30mW / cm 2 In the range of 5mW / cm 2 Up to 20mW / cm 2 In the range of 5mW / cm 2 Up to 10mW / cm 2 In the range of 10mW / cm 2 Up to 60mW / cm 2 In the range of 20mW / cm 2 Up to 60mW / cm 2 In the range of 30mW / cm 2 Up to 60mW / cm 2 In the range of 40mW / cm 2 Up to 60mW / cm 2 The range of , or another range specified herein. If desired, higher fluxes can be used to increase penetration and achieve microbial purification.

[0292] In some embodiments, the ES increasing light has a greater radiant flux than the ES releasing light. In some embodiments, the ES releasing light has a greater radiant flux than the ES increasing light. In some embodiments, the anti-inflammatory light has a greater radiant flux than the ES increasing light and / or the ES releasing light. In some other embodiments, the anti-inflammatory light has a lesser radiant flux than the ES increasing light and / or the ES releasing light.

[0293] In certain embodiments using a combination of wavelengths, one or both of the anti-inflammatory light and the ES increasing light and / or the ES releasing light have a radiant flux distribution that is substantially constant during the therapeutic window. In certain embodiments, at least one of the anti-inflammatory light and the ES increasing light and / or the ES releasing light has a radiant flux distribution that increases over time during the therapeutic window. In certain embodiments, at least one of the anti-inflammatory light and the ES increasing light and / or the ES releasing light has a radiant flux distribution that decreases over time during the therapeutic window. In certain embodiments, one of the anti-inflammatory light and the ES increasing light and / or the ES releasing light has a radiant flux distribution that decreases over time during the therapeutic window, while the other of the anti-inflammatory light and the ES increasing light and / or the ES releasing light has a radiant flux distribution that increases over time during the therapeutic window.

[0294] In certain embodiments, ES increasing light and / or ES releasing light is applied so that it increases nitric oxide levels in the brain, and thus increases angiogenesis in the brain. ES increasing light and / or ES releasing light can be applied during a first time window, and anti-inflammatory light can be applied during a second time window, wherein the anti-inflammatory light is applied to the desired area of ​​the brain, wherein the desired area of ​​the brain can be the same or different, and the second time window may overlap or not overlap with the first time window. In other embodiments, ES increasing light and / or ES releasing light is applied to the tissue during the first time window, anti-inflammatory light is applied to the tissue during the second time window, and the second time window does not overlap with the first time window. In certain embodiments, after the first time window ends, the second time window is activated for more than one minute, more than 5 minutes, more than 10 minutes, more than 30 minutes, or more than one hour. In certain embodiments, ES increasing light and / or releasing light is applied to the tissue during the first time window, anti-inflammatory light is applied to the tissue during the second time window, and the first time window and the second time window are substantially the same. In other embodiments, the second time window is longer than the first time window.

[0295] Aspects of these embodiments are also contemplated in which the UVA / UVB / UVC light is applied in the same or different time windows or to the same or different tissues.

[0296] In certain embodiments using a combination of wavelengths, one or both of the anti-inflammatory light and the ES increasing light and / or the ES releasing light can be provided by a steady state source that provides a substantially constant radiant flux over a long period of time without being pulsed.

[0297] In certain embodiments using a combination of wavelengths, one or both of the anti-inflammatory light and the ES increasing light and / or the ES releasing light may include more than one discrete pulse of light. In certain embodiments, more than one discrete pulse of ES increasing light and / or ES releasing light is irradiated onto the tissue during a first time window, and / or more than one discrete pulse of anti-inflammatory light is irradiated onto the tissue during a second time window. In certain embodiments, the first time window and the second time window may be coextensive, may overlap but not coextensive, or may not overlap.

[0298] In certain embodiments using a combination of wavelengths, during a portion of a first time window, at least one of the radiant flux and pulse duration of the ES increased light and / or the ES released light may decrease from a maximum value to a non-zero decreased value. In certain embodiments, during a portion of the first time window, at least one of the radiant flux and pulse duration of the ES increased light and / or the ES released light may increase from a non-zero value to a higher value. In certain embodiments, during a portion of a second time window, at least one of the radiant flux and pulse duration of the anti-inflammatory light may decrease from a maximum value to a non-zero decreased value. In certain embodiments, during a portion of the second time window, at least one of the radiant flux and pulse duration of the anti-inflammatory light may increase from a non-zero value to a higher value.

[0299] In certain embodiments using a combination of wavelengths, each of the ES increasing light and / or releasing light and the anti-inflammatory light consists of incoherent light. In certain embodiments, each of the anti-inflammatory light and the ES increasing light and / or ES releasing light consists of coherent light. In certain embodiments, one of the anti-inflammatory light and the ES increasing light and / or ES releasing light consists of incoherent light and the other consists of coherent light.

[0300] In certain embodiments using a combination of wavelengths, ES-enhancing light and / or ES-releasing light is provided by at least one first light-emitting device and anti-inflammatory light is provided by at least one second light-emitting device. In certain embodiments, ES-enhancing light and / or ES-releasing light is provided by a first array of light-emitting devices and anti-inflammatory light is provided by a second array of light-emitting devices.

[0301] In certain embodiments using a combination of wavelengths, at least one of the ES increase and / or ES release light and the anti-inflammatory light is provided by at least one solid-state light emitting device. Examples of solid-state light emitting devices include, but are not limited to, light emitting diodes, lasers, thin-film electroluminescent devices, powder electroluminescent devices, field-induced polymer electroluminescent devices, and polymer light-emitting electrochemical cells. In certain embodiments, the ES increase and / or ES release light is provided by at least one first solid-state light emitting device, and the anti-inflammatory light is provided by at least one second solid-state light emitting device. In certain embodiments, the anti-inflammatory light and the ES increase and / or ES release light can be generated by different emitters contained in a single solid-state emitter package, where the close spacing between adjacent emitters can provide overall color mixing. In certain embodiments, the anti-inflammatory light can be provided by a first array of solid-state light emitting devices and the ES increase and / or ES release light can be provided by a second array of solid-state light emitting devices.

[0302] In certain embodiments using wavelength combinations, an array of solid state emitter packages may be provided, each solid state emitter package comprising at least one first emitter and at least one second emitter, wherein the array of solid state emitter packages is embodied as a first array of solid state emitters arranged to produce ES increasing and / or ES releasing light, and is embodied as a second array of solid state emitters arranged to produce anti-inflammatory light. In certain embodiments, the array of solid state emitter packages may be embodied as a package further comprising a third, fourth, and / or fifth solid state emitter, such that a single array of solid state emitter packages may be embodied as three, four, or five solid state emitter arrays, each of which is arranged to produce emission having a different peak wavelength.

[0303] In certain embodiments using a combination of wavelengths, at least one of the anti-inflammatory light and the ES increasing light and / or the ES releasing light is provided by at least one light emitting device without a wavelength converting material.

[0304] In certain embodiments using a combination of wavelengths, the anti-inflammatory light consists of substantially monochromatic light and the ES-enhanced light and / or the ES-released light consists of substantially monochromatic light. In certain embodiments, the ES-enhanced light comprises a first spectral output having a first full-width half-maximum of less than 25 nm (or less than 20 nm, or less than 15 nm, or in a range of 5 nm to 25 nm, or in a range of 10 nm to 25 nm, or in a range of 15 nm to 25 nm), and / or the ES-released light comprises a second spectral output having a second full-width half-maximum of less than 25 nm (or less than 20 nm, or less than 15 nm, or in a range of 5 nm to 25 nm, or in a range of 10 nm to 25 nm, or in a range of 15 nm to 25 nm).

[0305] In certain embodiments using a combination of wavelengths, the anti-inflammatory light is generated by one or more first light emitters having a single first peak wavelength, and the ES-increasing light and / or the ES-releasing light is generated by one or more second light emitters having a single second peak wavelength. In other embodiments, the anti-inflammatory light may be generated by at least two light emitters having different peak wavelengths (e.g., differing by at least 5 nm, at least 10 nm, at least 15 nm, at least 20 nm, or at least 25 nm), and / or the ES-increasing and / or ES-releasing light may be generated by at least two light emitters having different peak wavelengths (e.g., differing by at least 5 nm, at least 10 nm, at least 15 nm, at least 20 nm, or at least 25 nm).

[0306] Ultraviolet light (e.g., UV-A light with a peak wavelength in the range of 350nm to 395nm, and UV-B light with a peak wavelength in the range of 320nm to 350nm) can be effective as ES increasing light; however, overexposure to UV light may not be preferred because it can cause tissue damage. That said, UVC light is also particularly effective in treating or preventing microbial infections. While damage to tissues should be minimal with exposure to these wavelengths, it may cause some adverse effects with long-term exposure. Therefore, it may be desirable to use a shorter UV light cycle than non-UV light.

[0307] In certain embodiments, UV light (eg, having a peak wavelength in the range of 320 nm to 399 nm) may be used as the ES-increasing light; however, in other embodiments, UV light may be avoided.

[0308] Combining these (UVA, UVB and / or UVC) wavelengths of light with anti-inflammatory light can minimize these effects.

[0309] In certain embodiments, the ES-enhanced light and the ES-released light are substantially free of UV light. In certain embodiments, less than 5% of the ES-enhanced light is within a wavelength range of less than 400 nm, and less than 1% of the ES-released light output is within a wavelength range of less than 400 nm. In certain embodiments, the ES-enhanced light comprises a peak wavelength within a range of 400 nm to 490 nm, or 400 nm to 450 nm, 400 nm to 435 nm, or 400 nm to 420 nm.

[0310] In certain embodiments, ES-enhanced light can include a wavelength range and flux that can alter the presence, concentration, or growth of bacteria or other microorganisms in or on tissue receiving the light. UV light and near-UV light (e.g., peak wavelengths of 400 nm to 435 nm, or more preferably 400 nm to 420 nm) can particularly affect microbial growth.

[0311] The effect on microbial growth may depend on the wavelength range and dose. In certain embodiments, the ES-enhanced light may include near-UV light with a peak wavelength in the range of 400 nm to 420 nm to provide a microbicidal / bacteriostatic effect (e.g., using a radiant flux of <9 mW / cm 2 pulsed light), providing a bactericidal effect (e.g., a radiation flux of 9 mW / cm 2 Up to 17mW / cm 2 range), or provide antimicrobial effects (e.g., radiant flux greater than 17 mW / cm 2 In the range, for example, 18mW / cm 2 Up to 60mW / cm 2 range of basic steady-state light).

[0312] In certain embodiments, in addition to increasing angiogenesis in the brain, ES-enhancing light in the near-UV range (e.g., 400 nm to 420 nm) can also affect microbial growth in the brain (whether in the microbicidal / bacteriostatic range, in the bactericidal range, or in the antimicrobial range). Thus, in addition to increasing angiogenesis, such light can also be used to inhibit infection in brain tissue.

[0313] In certain embodiments, the ES released light may include a peak wavelength in the range of 500nm to 900nm, or in the range of 490nm to 570nm, or in the range of 510nm to 550nm, or in the range of 520nm to 540nm, or in the range of 525nm to 535nm, or in the range of 528nm to 532nm, or in the range of about 530nm.

[0314] The wavelength at 660nm is both anti-inflammatory and releases NO.

[0315] An equal combination of 410nm light and 530nm light is as effective as 530nm light alone. This combination may be beneficial because 410nm blue LEDs are significantly more efficient than 530nm green LEDs, so an equal combination of 410nm LED emission and 530nm LED emission may reduce power consumption by 26% compared to the emission of a 530nm LED alone when operated to provide the same radiant flux.

[0316] In terms of releasing NO from Hb-NO, 660nm light is significantly less effective than 530nm green light. For 530nm green light, 660nm red light, and a combination of 530nm green light and 660nm light, the release of NO from Hb-NO appears to be the same in a time window from 0 seconds to about 2000 seconds, but thereafter, the effectiveness of different sources diverges. Without intending to be bound by any particular theory or explanation of this phenomenon, it is believed that NO binds to Hb-NO at multiple sites, and removing a second or subsequent NO molecule from Hb-NO may require more energy than removing the first NO molecule, which may be due to the change in the shape of the Hb-NO after removing the first NO molecule.

[0317] In some embodiments, anti-inflammatory light having a first peak wavelength is irradiated onto tissue surrounding the injected biosensor, and ES-increasing or ES-releasing light having a second peak wavelength is also irradiated onto the tissue, and light having a third peak wavelength (i.e., ES-releasing or ES-increasing light) may be irradiated onto the tissue. In some embodiments, light having a third peak wavelength may be provided at substantially the same time as one or both of the anti-inflammatory light and the ES-increasing light and / or the ES-releasing light (or during a time window overlapping at least one of the time windows).

[0318] In some embodiments, the light having the third peak wavelength differs from each of the first peak wavelength and the second peak wavelength by at least 10 nm. In some embodiments, the light having the third peak wavelength exceeds the second peak wavelength by at least 20 nm. In some embodiments, the light having the third peak wavelength is emitted at 5 mW / cm 2 Up to 60mW / cm 2 In some embodiments, the third peak wavelength is in the range of 600nm to 900nm, or in the range of 600nm to 700nm. In some embodiments, the third peak wavelength is in the range of 320nm to 399nm.

[0319] In certain embodiments, anti-inflammatory light is in the range of about 630 nm to 670 nm (e.g., including specific wavelengths of about 630 nm and about 660 nm), which can be used to provide anti-inflammatory effects and / or promote vasodilation. Anti-inflammatory effects can be used to treat, prevent or slow the progression of various central nervous system disorders.

[0320] In some embodiments, when one or more wavelengths of light are used, the light can be coherent or incoherent, or a mixture thereof.

[0321] In some embodiments where different wavelengths are administered, the light can be administered at different power densities / durations, for example to provide shorter UVC exposures to avoid damaging tissue, and longer anti-inflammatory wavelength exposures.

[0322] Producing neurotransmitters through exposure to specific wavelengths

[0323] Multiple CNS disorders are associated with decreased levels of various neurotransmitters. As discussed below, specific wavelengths of light can be used to enhance the production of various neurotransmitters. Serotonin is a neurotransmitter that affects memory and learning, regulates anger and aggression, and is a component of anxiety disorders such as depression and obsessive-compulsive disorder. When levels are too high, it can lead to Alzheimer's disease. Dopamine is a neurotransmitter that is associated with ADHD, hyperactive adults, bipolar disorder, and social anxiety, and also regulates pain. If dopamine levels are too high, psychosis or schizophrenia may result. Norepinephrine is associated with increased alertness, arousal, and reward systems. Acetylcholine deficiency has been associated with Alzheimer's disease and loss of memory and learning abilities.

[0324] According to some embodiments, light in the 260-400 nm range can be used to penetrate the orbit, the eye, and ultimately into deep brain structures in the frontal lobe to modulate dopamine levels due to tyrosinase.

[0325] A pigment in the human eye called melanopsin acts as a receptor that signals the production or suppression of melatonin, the hormone that regulates sleep and wakefulness. Melanoopsin is triggered by specific wavelengths of light and is most sensitive to wavelengths at and around 480nm.

[0326] ipRGCs (intrinsically photosensitive retinal ganglion cells) contain melanopsin, and shining the correct wavelength of light on the optic nerve and indirectly to the pineal gland can stimulate the production of neurotransmitters, hormones, and enzymes that can help treat certain behavioral and mood disorders. These cells are particularly sensitive to blue light, specifically blue light that has a peak around 470nm. By exposing patients to blue light, so that the light enters and falls on the lower back of the retina, the ipRGCs cause an increase in neurotransmitter levels.

[0327] When melanocortin receptors (MC4R) in the eye are exposed to the appropriate wavelength of light, memory impairment caused by the accumulation of fibrillar amyloid plaques can be reversed. Amyloid is stimulated by light, especially blue light. Blue light triggers the MC4R receptors in the eye and hypothalamus and keeps the protein active so that it does not form amyloid plaques.

[0328] Blue light reduces nocturnal melatonin, and both blue and red light affect cortisol and alpha amylase levels (see, e.g., Figueiro MG, Rea MS. The effects of red and blue lights on circadian variations in cortisol, alpha amylase, and melatonin. Int J Endocrinol. 2010; 2010: 829351).

[0329] In the absence of optogenetic proteins, blue light can increase the expression of genes regulated by neuronal activity. One hour of exposure to blue light (but not red or green light) led to increased expression of genes regulated by neuronal activity.

[0330] The frequency of the pulsed light also has an effect. For example, when blue light is pulsed from 10 Hz to 100 Hz, a 3-fold increase in expression can be obtained compared to emitting light at a frequency outside of this range at the same wavelength for the same exposure duration.

[0331] The location of light exposure

[0332] Some diseases are not region-specific. That is, they are not necessarily caused by damage to a specific area of ​​the brain but occur in different locations throughout the brain or in each patient, such as Creutzfeldt-Jakob disease, hypothyroidism, dementia with Lewy bodies, normal pressure hydrocephalus, tauopathy, and vascular dementia.

[0333] For example, with vascular dementia, blood vessels throughout the brain may be affected, with some more affected than others. In treating these disorders, light can be applied throughout the head. For inflammation-based diseases, such as Parkinson's, the more brain areas that can be treated, the better the treatment. For some diseases, treatment can be applied to acupuncture points in the brain.

[0334] In some embodiments, treatment is applied to a specific hemisphere of the brain, although this level of specificity need not be used. For example, Alzheimer's disease can be treated by targeting the frontal cortex, temporal lobe, and base. Amyotrophic lateral sclerosis (ALS) can be treated by targeting the motor cortex. Autism spectrum disorders can be treated by targeting the frontal cortex, temporal lobe, and / or base of the skull. Epileptic seizures can be treated by targeting the cortex. Huntington's disease can be treated by targeting the basal ganglia. Parkinson's disease can be treated by targeting the midbrain. Pick's disease and other frontotemporal dementias can be treated by targeting the frontal lobe.

[0335] Use of pulse frequency

[0336] Regardless of the device used, the applied light energy can be applied at a pulse frequency that simulates healthy brain function of alpha, beta, delta and theta waves. The pulse frequencies can be applied in series, alternately or simultaneously. The light can be emitted from the same light emitter or from multiple emitters. The frequency range of delta waves is about 0.5 to 3 Hz, and their main source location in the human brain is the thalamus or cortex. The suitable frequency range of theta waves is 3 to 8 Hz, and their main source location in the human brain is the hippocampus. The frequency range of alpha waves is about 8 to 12.5 Hz, and their main source location in the human brain is the occipital lobe. The frequency range of μ waves is about 7.5 to 12.5 Hz, mainly between 9 and 11 Hz, and their main source location in the human brain is the motor cortex. The frequency range of beta waves is about 12.5 to 38 Hz, and their main source location in the human brain is the hindbrain. The frequency range of gamma waves is about 38 to 100 Hz, and is located in all areas of the brain.

[0337] In some embodiments, light energy is applied at a pulse frequency of about 40Hz, which can be used to treat Alzheimer's disease by reducing amyloid plaques. In some embodiments, light energy with a frequency of about 30Hz to about 50Hz and more specifically about 40Hz is delivered non-invasively to the subject to entrain gamma oscillations in multiple brain regions of the subject. These regions include the prefrontal cortex (PFC) and the hippocampus, and may further include the visual cortex, somatosensory cortex, hippocampus, and prefrontal cortex of the subject. This light energy can be applied alone or in combination with a chronic visual stimulation with a frequency of about 30Hz to about 50Hz and more specifically about 40Hz. Entrained gamma oscillations regulate neuronal activity across multiple brain regions (e.g., promoting functional binding of neural networks at low gamma frequencies) to induce various neuroprotective effects (e.g., improvements in amyloid plaques and tau hyperphosphorylation) and reduce neurodegeneration.

[0338] Neuronal activity reduced microglial immune responses and improved abnormally modified genes and proteins involved in membrane trafficking, intracellular trafficking, synaptic function, neuroinflammation, and DNA damage response. Behavioral modification can be achieved, including enhanced learning and memory.

[0339] In other embodiments, light energy is applied at a pulse frequency in the alpha, beta, delta and / or theta wave range and this helps treat Parkinson's disease.

[0340] Pulsed electromagnetic field therapy, including pulsed frequencies in the same range, can be used in combination with the light therapy described herein, even in embodiments where the light is not pulsed. Pulsed electromagnetic field therapy (PEMFT, or PEMF therapy), also known as low-field magnetic stimulation (LFMS), treats patients through the use of electromagnetic fields. Most PEMF health devices are similar in size to a typical yoga mat, but are slightly thicker to accommodate multiple flat spiral coils to produce a uniform electromagnetic field. A frequency generator energizes the coils to produce a pulsed electromagnetic field.

[0341] V. Treatment Methods

[0342] The methods described herein can be used to treat a variety of CNS disorders, particularly diseases with an inflammatory component, and / or diseases associated with poor vascularization of one or more regions of the brain. These disorders include cognitive disorders, movement disorders, and behavioral / mood disorders.

[0343] In addition, the passage of light of the appropriate wavelength can heal damage to the blood-brain barrier and help drugs pass through the blood-brain barrier. Therefore, this method can be used to assist in the treatment of brain cancer and other brain diseases.

[0344] The method comprises applying light at a suitable wavelength or combination of wavelengths, at a suitable power, and for a suitable period of time to the brain of a patient in need of treatment for a cognitive disorder to treat the disorder.

[0345] In disorders with an inflammatory component, light may be administered at an anti-inflammatory wavelength. In disorders with a vascular component, light may be administered at a wavelength that promotes increased angiogenesis, for example by promoting the production and / or release of endogenous NO.

[0346] In some embodiments, light is applied generally to the brain. In other embodiments, light is applied near an area of ​​the brain that is malfunctioning or associated with the source of the disease to be treated.

[0347] In yet other embodiments, therapy is enhanced by activating cranial nerves while applying light.

[0348] According to information and belief, it takes at least one week, and in some cases about 2-4 weeks of treatment to see beneficial effects, with the therapeutic effects declining within two weeks to a month after the end of treatment.

[0349] Types of conditions that can be treated

[0350] The treatments described herein can be used to treat a variety of different disorders, including neurocognitive disorders, movement disorders, and emotional / behavioral / mood disorders.

[0351] The treatment may also increase the flux of drugs across the blood-brain barrier and therefore be useful in treating brain disorders, such as cancer, or disorders associated with a compromised blood-brain barrier.

[0352] Disorders associated with impaired blood-brain barrier

[0353] Disorders associated with a compromised blood-brain barrier include Alzheimer's disease (van de Haar HJ, et al., "Blood-Brain Barrier Leakage in Patients with Early Alzheimer Disease". Radiology. 282(2): 615 (February 2017)), anxiety and depression (Gal Z, Huse RJ, Gonda X, Kumar S, Juhasz G, Bagdy G, Petschner P (March 2019). "Anxiety and depression-the role of blood-brain barrier integrity" . Neuropsychopharmacologia Hungarica. 21(1): 19-25), brain abscesses (caused by inflammation and lymphocyte accumulation and infectious material originating from local or remote infections), De Vivo disease (also known as GLUT1 deficiency syndrome, caused by inadequate transport of the sugar glucose across the blood-brain barrier, usually caused by genetic defects in the type 1 glucose transporter (GLUT1), HIV encephalitis (Ivey NS, MacLean AG, Lackner AA (April 2009). "Acquired immunodeficiency syndrome and the blood-brain barrier". Journal of Neurovirology. 15(2): 111-22), meningitis (related to inflammation of the membranes that surround the brain and spinal cord, the meninges), multiple sclerosis (Waubant E (2006). "Biomarkers indicative of blood-brain barrier disruption in multiple sclerosis". Disease Markers. 22(4): 235-44), and neuromyelitis optica, also known as Devic's disease, which is similar to multiple sclerosis.

[0354] Types of Brain Cancer

[0355] Representative types of brain cancer that can be treated include astrocytomas, including gliomas, glioblastoma multiforme and meningiomas, ependymomas, pituitary tumors, such as pituitary adenomas and pituitary carcinomas, craniopharyngiomas, germ cell tumors, such as germ cell tumors, pineal region tumors, including slow-growing (pineocytoma) and rapidly growing (pineoblastoma) tumors, medulloblastomas and primary central nervous system lymphomas.

[0356] When used to treat brain cancer, conventional anticancer drugs can be used to enhance their passage through the blood-brain barrier, thereby maximizing the therapeutic efficiency. Representative anticancer drugs include 5FC, Accutane, AEE788 (Novartis), AMG-102, Anti Neoplaston, AQ4N (Banoanthraquinone), AVANDIA (Rosiglitazone Maleate), Avastin (Bevacizumab), BCNU, BiCNU, Carmustine, Carboplatin, CC-223, CC223, CCI-779, CCNU, CCNU Lomustine, Celecoxib (systemic), Chloroquine, Cilengitide (EMD 121974), cisplatin, CPT-11 (CAMPTOSAR, irinotecan), cyclophosphamide, dasatinib (BMS-354825, Sprycel), etoposide (Eposin, Etopophos, Vepesid), GDC-0449, Gleevec (imatinib mesylate), GLIADEL wafer, hydroxychloroquine, hydroxyurea, IL-13, IMC-3G3, immunotherapy, Iressa (ZD-1839), lapatinib (GW572016), methotrexate, Novocure, OSI-774, PCV, procarbazine, RAD001 Novartis (mTOR inhibitor), rapamycin (rapamycin, sirolimus), RMP-7, RTA 744, simvastatin, sirolimus, sorafenib, SU-101, SU5416 Sugen, sulfasalazine (Azulfidine), Sutent (Pfizer), tamoxifen, Tarceva (erlotinib hydrochloride), paclitaxel, temozolomide, temozolomide Schering-Plough, Thalomid (thalidomide), Toca 511, topotecan (systemic), VEGF trap, VEGF-trap, Velcade, vincristine, vorinostat (SAHA), XL 765, XL-184, XL184, XL765, Zarnestra (tibifarnib), and Zocor (simvastatin). Dexamethasone and furosemide can be used to reduce swelling.

[0357] Conventional antimicrobial agents may also be used as adjuncts to the treatment of brain infections.

[0358] CNS disorders associated with inflammation

[0359] Central nervous system (CNS) vasculitis is an inflammation of the blood vessel walls in the brain or spine that constitute the central nervous system. CNS vasculitis is often accompanied by other autoimmune diseases, such as systemic lupus erythematosus, dermatomyositis and rare rheumatoid arthritis. It is usually caused by viral or bacterial infection and can be systemic. When vasculitis is only confined to the brain or spinal cord, it is referred to as primary CNS vasculitis (PACNS).

[0360] Neurocognitive disorders

[0361] There are many neurocognitive disorders (also called cognitive disorders) that can be treated using the methods of treatment described herein. Examples include Alzheimer's disease, amnesia, Binswanger's disease, cerebellar cognitive affective syndrome, clinical dementia rating, confusion, cognitive deficits, cognitive slippage, cognitive susceptibility, corticobasal degeneration, corticobasal syndrome, delirium, dementia, disability affecting intellectual ability, frontal assessment battery, frontal temporal dementia, frontotemporal dementia and parkinsonism linked to chromosome 17, frontotemporal dementia and parkinsonism linked to chromosome 17, frontotemporal dementia, HIV-related neurocognitive disorders, learning problems in childhood cancer, Lewy body dementia association, Lewy body dementia, logopenic progressive aphasia aphasia), mild cognitive impairment, paratonia, Pick's disease, post-chemotherapy cognitive impairment, postoperative cognitive dysfunction, primary progressive aphasia, progressive nonfluent aphasia, progressive supranuclear palsy, pseudosenility, REM sleep behavior disorder, semantic dementia, severe cognitive impairment, subcortical dementia, and vascular dementia.

[0362] Neurocognitive disorders can have a variety of causes, including genetics, brain trauma, stroke, and heart problems. The main causes are neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, as they affect or worsen brain function. Other diseases and conditions that lead to NDC include vascular dementia, frontotemporal lobar degeneration, Lewy body disease, prion disease, normal pressure hydrocephalus, and dementia / neurocognitive problems caused by HIV infection. They can also include dementia caused by substance abuse or exposure to toxins.

[0363] Neurocognitive disorders also include brain trauma, including concussions and traumatic brain injuries, as well as post-traumatic stress and alcohol abuse. This is called amnesia, and is characterized by damage to the main memory encoding part of the brain, such as the hippocampus. Difficulty creating recent memories is called anterograde amnesia, which is caused by damage to the hippocampus part of the brain. Retrograde amnesia is also caused by damage to the hippocampus, but memories that have been encoded or are being encoded in long-term memory are erased.

[0364] Movement disorders

[0365] Movement disorders are clinical syndromes of excessive or insufficient voluntary and involuntary movements that are not associated with weakness or spasticity and are generally divided into two major categories - hyperkinetic and hypokinetic. Hyperkinetic movement disorders refer to movement disorders or excessive, often repetitive, involuntary movements that disrupt the normal flow of motor activity. Hypopneic movement disorders refer to akinesia (lack of movement), hypokinesia (reduced range of movement), bradykinesia (slow movements), and rigidity. In primary movement disorders, abnormal movements are the primary manifestation of the disorder. In secondary movement disorders, abnormal movements are a manifestation of another systemic or nervous system disorder.

[0366] Representative movement disorders include hypokinetic movement disorders, Parkinson's disease (primary or idiopathic Parkinson's disease), secondary Parkinson's disease, Parkinson's plus syndrome, Hallervorden-Spatz disease, progressive supranuclear ophthalmoplegia, striatonigral degeneration, hyperkinetic movement disorders, dystonias including drug-induced dystonias, idiopathic familial dystonias, idiopathic non-familial dystonias, idiopathic orofacial dystonias, spasmodic torticollis, blepharospasm and other dystonias, extrapyramidal movement disorders, essential tremor, drug-induced Tremor, myoclonus, opsoclonus, chorea (rapid, involuntary movements), including drug-induced chorea, rheumatic chorea (Sydenham's chorea), and Huntington's disease, tics (violent involuntary rapid and irregular movements), unilateral tics (affecting only one side of the body), athetosis (distorting twisting or twisting), dyskinesias (abnormal, involuntary movements), tardive dyskinesia, tic disorders (involuntary, compulsive, repetitive, stereotyped), including Tourette syndrome and drug-induced tics and tics of organic origin, stereotypic movement disorders, paroxysmal nocturnal limb movements, leg (or arm) pain, toe (or finger) movement syndrome, sporadic restless legs syndrome, familial restless legs syndrome, stiff-person syndrome, abnormal head movements, cramps and spasms, and fasciculations.

[0367] Emotional / Behavioral / Mood Disorders

[0368] Emotional and behavioral disorders (EBD; also called behavioral and emotional disorders (ICD-10)) are a disability classification used in educational settings to allow educational institutions to provide special education and related services to students who are experiencing poor social and / or academic progress.

[0369] Disruptive behavior disorders include attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD). Schizophrenia is also included in this definition.

[0370] Anxiety disorders are also included. Representative anxiety disorders include generalized anxiety disorder, specific phobia, social anxiety disorder, separation anxiety disorder, agoraphobia, panic disorder, and selective mutism. Anxiety disorders often co-occur with other mental disorders, especially major depressive disorder, personality disorders, and substance use disorders.

[0371] Depression includes major depressive disorder (MDD, also called major depressive disorder, unipolar depression, or clinical depression) and has multiple subtypes or course specifiers, including atypical depression (AD), melancholic depression, psychotic major depression (PMD, or simply psychotic depression), catatonic depression, postpartum depression, premenstrual dysphoric disorder (PMDD), seasonal affective disorder (SAD), dysthymia, double depression, depressive personality disorder (DPD), recurrent brief depressive disorder (RBD), minor depressive disorder (minor depression), and depressive disorder not otherwise specified (DD-NOS), which includes "any depressive disorder that does not meet the criteria for a specific disorder."

[0372] Bipolar disorder (BD, also called manic-depressive illness or manic-depressive disorder), includes bipolar I, bipolar II, cyclothymia, and bipolar disorder not otherwise specified (BD-NOS, or "subthreshold" bipolar).

[0373] Some mood disorders are substance-induced, including alcohol-induced and benzodiazepine-induced.

[0374] Medications, such as antidepressants, benzodiazepines, or beta blockers, may be used in combination with the treatments described herein.

[0375] Specific pharmacological treatment options for each of the disorders discussed in this article are outlined below.

[0376] Combination therapy for Parkinson's disease

[0377] Although Parkinson's disease cannot be cured, many different types of medications can provide some relief. The main families of drugs used to treat motor symptoms are levodopa (usually combined with a dopa decarboxylase inhibitor and sometimes a COMT inhibitor), dopamine agonists, and MAO-B inhibitors. Representative dopamine agonists include bromocriptine, pergolide, pramipexole, ropinirole, piperibedil, cabergoline, apomorphine, and lisuride. Representative MAO-B inhibitors include safinamide, selegiline, and rasagiline.

[0378] Those skilled in the art understand that the stage of the disease and the age of onset determine which group is most useful. The Braak staging system for Parkinson's disease gives six stages that can be used to identify early, late, and terminal stages. An initial stage in which some disability has developed and requires medication is followed by a later stage associated with the development of complications related to levodopa use, and a third stage in which symptoms unrelated to dopamine deficiency or levodopa treatment may predominate.

[0379] Typically, only 5-10% of levodopa crosses the blood-brain barrier. Most of the rest is metabolized to dopamine elsewhere in the body, causing a variety of side effects, including nausea, vomiting, and postural hypotension.

[0380] Carbidopa and benserazide are dopa decarboxylase inhibitors that do not cross the blood-brain barrier and inhibit the conversion of levodopa to dopamine outside the brain, thereby reducing side effects and increasing the availability of levodopa into the brain. One of these drugs is often taken with levodopa, usually in the same pill.

[0381] Because the treatments described herein can increase the passage of drugs across the blood-brain barrier, the dose of levodopa can be reduced while still achieving the same degree of efficacy and, therefore, reducing side effects, including dyskinesias.

[0382] Enteral infusion of levodopa can also be used and may reduce dose fluctuations relative to oral levodopa.

[0383] Catechol-O-methyltransferase (COMT) inhibitors such as apicapone, entacapone and tolcapone can be used in combination with levodopa and dopamine decarboxylase (DDC) inhibitors to inhibit peripheral levodopa metabolism and increase the amount of levodopa delivered to the brain. Other drugs such as amantadine, anticholinergics, quetiapine, cholinesterase inhibitors, modafinil, pimavanserin, doxepin and rasagiline can also be used.

[0384] Combination therapy for Alzheimer's disease and other cognitive disorders

[0385] In addition to the treatment described herein, a variety of drugs have been developed for Alzheimer's patients, which can be used in combination with the treatment. Representative compounds that can be administered include memantine, solanimumab, aducanumab, compounds that reduce beta-amyloid levels, such as apomorphine and aducanumab, vaccines that train the immune system to recognize, attack and reverse amyloid deposition, such as ACC-001 and bapinezumab, and antisense therapy, neuroprotectants, such as AL-108, metal-protein interaction reducers, such as PBT2, TNFα receptor blockers, such as fusion proteins, etanercept, tau aggregation inhibitors, such as methylthionium chloride and its prodrug LMTX, antihistamines (such as dimebon) and beta-secretase protein inhibitors (such as verubicin) that can reduce beta-amyloid concentrations. Drugs that reduce oxidative stress can improve memory and can therefore be administered together. Treatments that reduce amyloid-β can not only improve memory, but also reduce oxidative stress.

[0386] As discussed elsewhere herein, in animal models, such as the accelerated senescence mouse (SAMP8) model, amyloid precursor protein (APP) is overproduced, the blood-brain barrier is impaired, resulting in reduced excretion of amyloid-β from the brain and increased oxidative stress in the brain.

[0387] Use of the treatments described herein may increase the ability of agents to cross the blood-brain barrier, thereby enhancing the effectiveness of these agents, as well as accelerating the excretion of amyloid-β from the brain.

[0388] Additional combination therapy

[0389] In addition to the light and medication-assisted therapies discussed herein, other treatments that may be used in combination with light include PEMF or other magnetic field therapy, Traditional Chinese Medicine / color needling, stimulating acupuncture / trigger points (1-40mm), Bonghan channel hyaluronic acid / stem cell therapy, behavioral health / spiritual therapy (cognitive behavioral, biofeedback, EMDR, and / or deep relaxation).

[0390] VI. Methods of following the treatment process

[0391] There are various ways to monitor the progress of treatment and the specifics depend on whether the CNS disorder being treated is a cognitive, movement or behavioral disorder or a brain tumor.

[0392] For many of these disorders, treatment can be followed by, for example, tracking blood pressure, blood flow, pulse, heart rate variability, blood oxygen saturation, electrocardiographic response, respiratory rate, breathing pattern, galvanic skin response, pupil dilation, trabecular-ciliary process distance, magnetic resonance imaging, brain waves, body movement, muscle tension, self-report, and combinations thereof.

[0393] The treatment session may first explain the proposed treatment to the patient in the usual manner of any medical procedure, and discuss the risks and benefits of different approaches. The patient may be placed in a chair, bed, enclosure, etc., and a suitable light emitting device as described herein may be applied to the patient.

[0394] Power can then be supplied to the light source and other components of the light therapy system. In some embodiments, an operator, who may be a patient, can input a desired wavelength, duration, intensity, and / or treatment time. Using these settings, light is emitted to the patient, in some embodiments, such that it can pass through the skull and / or brain for a given length of time.

[0395] One method of monitoring the success of treatment is to measure various parameters while the treatment is being administered. For example, a detector (e.g., a photodiode, phototransistor, photoresistor, etc.) can record transmitted and scattered light, either for informational purposes or to control one or more system functions. At the end of the treatment period, the lamp and any detection devices can be deactivated, and the patient can be notified that treatment has ended. After treatment is completed, the results of the phototherapy can be evaluated through a review procedure.

[0396] Additionally or alternatively, a patient physiological monitor can be used as a feedback source, which is connected to the feedback / control line to provide feedback that can be used to perform active control (e.g., amplitude control, etc.) of the dose (e.g., intensity, duration, wavelength, etc.) provided by the light source. The patient physiological monitor can monitor one or more aspects of the patient to look for signs of effective dose and the amount of energy delivered to the internal target area. For example, the monitor can analyze the patient's exhaled air to identify increased nitric oxide concentrations in the exhaled air, indicating that the brain is stimulated to produce more endogenous nitric oxide. Similarly, the patient's blood pressure can be assessed because nitric oxide can control blood flow and blood pressure by activating the heme enzyme, soluble guanylate cyclase.

[0397] The system may optionally include looking for levels of light absorbers / scatterers, such as cytochrome c oxidase or hemoglobin (in its oxygenated and deoxygenated states). Spectrophotometric measurements may be made using one or more wavelengths, thereby performing noninvasive measurements of various biochemical processes. The information so obtained can help identify and maintain appropriate light dosage during treatment and determine the required and / or minimum effective dose.

[0398] Similarly, one can identify other parameters suitable for a treatment session, for example, by varying wavelength, intensity, and / or time and looking for appropriate physiological responses. For example, instead of starting with a minimum dose and gradually increasing the dose, a base wavelength can be used initially and gradually adjusted to determine the optimal wavelength. To this end, a feedback system can be used to non-invasively identify desired operating parameters of near-IR light entering a target area, such as identifying the minimum light dose required to perform a desired treatment on the target area.

[0399] These methods can provide near-instant feedback on whether a treatment is working. However, it is also important to track the course of treatment over time to determine if the disease state has been eliminated, its progression has been reversed, or its progression appears to have slowed. The steps for long-term monitoring will vary depending on the disease being treated.

[0400] Long-term monitoring of cognitive impairment

[0401] When treating cognitive impairment, such as Alzheimer's disease (AD), mild cognitive impairment (MCI), traumatic brain injury (TBI), etc., the success of treatment can be regularly assessed using mental acuity tests. One of these tests is the Mini-Mental State Examination (MMSE) or Folstein test, which is a 30-point questionnaire widely used in clinical and research settings to measure cognitive impairment. It is often used to screen for dementia, and to estimate the severity and progression of cognitive impairment, and to track the course of cognitive changes in an individual over time. Therefore, it is an effective way to record an individual's response to treatment.

[0402] Test administration (the standard MMSE form currently published by Psychological Assessment Resources) takes 5 to 10 minutes and examines function, including the ability to hold register (repeat naming prompts), attention and calculation, recall, language, follow simple commands, and orientation.

[0403] The MMSE has validity and reliability in diagnosing and assessing Alzheimer's disease and other cognitive disorders. Other tests, such as the Hawkinson Abbreviated Mental Test Score, the Geriatric Mental State Examination (GMS) or General Practitioner Cognitive Assessment, bedside tests such as the 4AT (which also assesses delirium), and computerized tests such as the CoP and the Mental Attributes Analysis System, as well as longer formal tests for more in-depth analysis of specific deficits, may also be used.

[0404] In addition to these tests, a brain scan may be performed, for example using SPECT, PET or MRI imaging techniques. Additional devices that may be used include functional near-infrared spectroscopy (fNIRS) devices, magnetoencephalography (MEG) devices, and electroencephalography (EEG) devices.

[0405] If these brain scans are performed while treatment is being administered, one or more operating parameters of the light energy, such as wavelength, flux, fluence, and / or treatment time, may be adjusted based on analysis of the subject's brain activity.

[0406] As disclosed in U.S. Pat. No. 9,950,189, SPECT functional neuroimaging can be used for targeted therapy followed by quantitative analysis, and neurophysiological testing can be used to target spinal cord or nerve-related disorders followed by quantitative analysis. Serial SPECT neuroimaging, coupled with quantitative analysis and / or the use of serial neurophysiological testing followed by quantitative analysis can elucidate changes in response to therapy.

[0407] In one embodiment, a first SPECT neuroimaging scan of the patient is obtained and analyzed to identify one or more areas of the patient's brain to be treated. Light is targeted to these areas. A second SPECT scan may be performed and analyzed in conjunction with the first SPECT scan to assess and characterize changes in the neurological disorder. In addition to SPECT scans, PET and MRI scans may also be used.

[0408] Those skilled in the art know how to perform perfusion single photon emission computed tomography (SPECT) scanning (see, for example, Raji CA, et al. Clinical utility of SPECT neuroimaging in the diagnosis and treatment of traumatic brain injury: a systematic review. PLoS One. 2014; 9(3): e91088, 2014).

[0409] Particularly for cognitive disorders, such as mild cognitive impairment (MCI), neuroimaging, particularly SPECT neuroimaging with quantitative analysis, can diagnose these disorders with an accuracy typically in the high 80% range (see, e.g., Henderson, T A. The diagnosis and evaluation of dementia and mild cognitive impairment with emphasis on SPECT perfusion neuroimaging. CNS Spectrums, 17(4): 176-206, 2012). SPECT neuroimaging is very helpful for evaluating CNS disorders with a vascular component, such as vascular dementia.

[0410] Perfusion SPECT can also be used to distinguish IPD from other parkinsonian syndromes, such as MSA or PSP (see, e.g., Markus HS, et al., HMPAO SPECT in Parkinson's disease before and after levodopa: correlation with dopaminergic responsiveness. J Neurol Neurosurg Psychiatry, 57: 180-185, 1994). A gradual increase in striatal perfusion is associated with an increase in symptom severity. The correlation between changes in striatal perfusion (or glucose metabolism) and disease symptom progression has been recognized (Kuhl DE, et al., Patterns of local cerebral glucose utilization determination in Parkinson's disease by the F18-fluorodeoxyglucose method. Ann Neurol, 1984; 15: 419-424, 1984).

[0411] Perfusion SPECT can also be used to assess PTSD. For example, increased perfusion of the caudate nucleus is associated with PTSD (see, e.g., Sachinvala N, et al., Increased regional cerebral perfusion by 99mTc hexamethylpropylene amine oxime single photon emission computed tomography in post-traumatic stress disorder. Mil Med. 165 (6): 473-9, 2000). Compared with controls, cerebral blood flow increased in the limbic region of PTSD patients, while perfusion decreased in the superior frontal, parietal and temporal regions (Chung YA, et al. Alterations in cerebral perfusion in posttraumatic stress disorder patients without re-exposure to accident-related stimuli. Clinical neurophysiology: official journal of the Int. Fed. Clin Neurophysiol. 117 (3): 637-42, 2006).

[0412] SPECT scans of patients with TBI and / or PTSD allow a high degree of discrimination between the different states compared to controls.

[0413] SPECT can be used to assess neurological changes after treatment, particularly when combined with quantitative analysis using, for example, the techniques disclosed in (Henderson and Monies, SPECT Perfusion Imaging Demonstrates Improvement of Traumatic Brain Injury With Transcranial Near-infrared Laser Phototherapy. Adv Mind Body Med. 29(4): 27-33, 2015). SPECT combined with quantitative analysis can detect differences in neurological function in patients receiving treatment as described herein. For example, this can be measured by assessing increases in cerebral perfusion.

[0414] Long-term monitoring of movement disorders

[0415] Parkinson's disease is one of the most common movement disorders. There are five recognized stages of Parkinson's disease. In stage one, symptoms are mild and seen on only one side of the body (unilateral involvement), and there is usually little or no functional impairment. Stage two is characterized by symptoms on both sides of the body (bilateral involvement) or the midline, but without balance impairment, and may appear months or years after stage one. Stage three is considered intermediate and is characterized by loss of balance and slowness of movements. In stage four, PD has progressed to a severely disabling disease. Patients with stage four PD may be able to walk and stand independently, but they have a significant loss of ability. Stage five is the most advanced stage and is characterized by an inability to rise from a chair or get out of bed without assistance, a tendency to fall when standing or turning, and stiffening or stumbling when walking.

[0416] Initial diagnosis of movement disorders such as Parkinson's disease can also be made in the doctor's office, especially if the patient has tremors or shaking, slow movements (called bradykinesia), stiffness or rigidity in the arms, legs, or trunk, and / or balance problems or frequent falls. The neurologist can determine the movement of the patient's arms and legs and check muscle tone and balance. The patient may fill out a medical history questionnaire that asks questions about other medical conditions the patient has, medications the patient is taking, whether certain activities (handwriting, pressing buttons, etc.) are more difficult, whether the patient has changes in his voice (i.e., lighter voice and / or slurred speech), changes in the sense of smell, or sleep, memory, and / or mood problems.

[0417] Blood tests and / or brain scans can be used to rule out other conditions. A blood test can identify dopamine deficiency, in which case a drug called carbidopa-levodopa may be prescribed. Additionally or alternatively, a brain imaging test called DaTscan uses a small amount of radioactive drugs and a special scanner called a single photon emission computed tomography (SPECT) scanner to determine dopamine levels in the brain. This initial data can form a baseline, and the patient can be measured against this baseline after the treatment process described herein. The treating physician can confirm the ability to improve symptoms or slow down the progression of symptoms.

[0418] The diagnosis and treatment of synucleinopathies, such as Parkinson's disease and dementia with Lewy bodies, could be aided by using assays that identify and quantify pathogenic disease-associated forms of α-synuclein (αSynD). Two recent αSynD seed expansion tests provide the first prototypes for ultrasensitive and specific detection of αSynD in patients' cerebrospinal fluid (CSF). Another α-synuclein real-time tremor-induced conversion (αSyn RT-QuIC) assay with similar sensitivity and specificity to these assays is disclosed in Groveman, et al., "Rapid and ultra-sensitive quantitation of disease-associated α-synuclein seeds in brain and cerebrospinal fluid by αSyn RT-QuIC," Acta Neuropathol Commun 6, 7 (2018). These assays involve collecting a CSF sample and quantifying the relative amount of αSynD seeding activity in the CSF sample. These assays allow for quantification of this observed activity even in the early symptomatic stages of synucleinopathies. One can monitor treatment progress by obtaining a baseline measurement and repeating it periodically during treatment.

[0419] Long-term monitoring of movement disorders

[0420] Symptoms vary depending on the type of behavioral disorder, but often include anxiety, compulsive behaviors, unusual behaviors, behaviors that interfere with the ability to function adequately in daily life, social problems, and / or panic attacks.

[0421] An initial diagnosis of a conduct disorder may include standardized questionnaires, interviews with the child and his or her parents and teachers, and a formal diagnosis by a pediatrician, psychiatrist, or child psychologist.

[0422] Based on the results of this assessment, the patient may be diagnosed with attention deficit hyperactivity disorder (ADHD), autism, Asperger's syndrome, Tourette syndrome, drug or alcohol abuse, gambling addiction, agoraphobia, anorexia nervosa, binge eating disorder, bipolar disorder, bulimia nervosa, depression, depressive disorder, dysthymia, eating disorders, generalized anxiety disorder, mood disorders, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder (PTSD), social phobia, or specific phobias.

[0423] Many of these disorders are associated with underlying neurological abnormalities (see, e.g., Kaye W, et al. Neurobiology of anorexia and bulimia nervosa. Physiol Behav 2008 Apr 22; 94(1): 121-35). The treatments described herein can address these abnormalities, for example by reducing inflammation, inducing angiogenesis, and / or increasing the levels of various neurotransmitters.

[0424] There are recognized home tests that can monitor patients over time, at least for ADHD and other disorders of attention, overall mental health, and emotional stress, etc. These tests can be used to monitor the success of the treatments described herein over time.

[0425] Any patents, applications and other references that may be listed in accompanying or subsequent filing documents, as well as those listed above, are incorporated herein by reference in their entirety. If necessary, various aspects of the embodiments can be modified to employ the systems, functions, and concepts of the various references to provide further embodiments.

[0426] The contents of each reference cited herein are incorporated by reference in their entirety for all purposes.

[0427] Embodiments according to the inventive subject matter are described herein in detail to provide precise features of representative embodiments within the overall scope of the inventive subject matter. The inventive subject matter should not be construed as limited to such details.

Claims

1. A light emitting device, comprising: A plurality of light sources, wherein the average distance between each light source and its nearest neighbor is at least 8 mm; and at least a first attachment feature, The plurality of light sources include: a first group of light sources configured to emit light including NIR along an emission ray axis in a first direction and a second group of light sources configured to emit visible light along an emission ray axis in a second direction, wherein the first direction and the second direction are at least 50 degrees apart from each other, and The first attachment feature is configured to hold the light emitting device in a spaced relationship relative to a first structure, the first attachment feature being located on the first structure; Wherein, the first group of light sources includes two or more NIR emitters and the second group of light sources includes two or more visible light emitters, each of the two or more NIR emitters has a corresponding emission ray axis, and the corresponding direction of the ray axis is within 10 degrees of the first direction; and each of the visible light emitters has a corresponding emission ray axis, and the corresponding direction of the ray axis is within 10 degrees of the second direction.

2. The apparatus of claim 1, further comprising a piece of furniture selected from the group consisting of a headboard and a chair back; The piece of furniture comprises a first furniture surface and a second furniture surface, and The first attachment feature engages the first furniture surface and the second furniture surface.

3. The device according to claim 1 further comprises at least a first sensor selected from the group of sensors consisting of: an identity sensor, a human body sensor, a feature sensor, a head sensor, a head orientation sensor, a face sensor, a weight sensor, a brain wave sensor, a pulse sensor, a breathing sensor, a body temperature sensor, a blood pressure sensor, an oxygenation sensor, a skin resistance sensor, a skin temperature sensor, a motion sensor, a vibration sensor, an impact sensor, an eye state sensor, a body movement sensor, a clothing detector, an ambient temperature sensor, an ambient humidity sensor, an ambient noise sensor and a global positioning sensor.

4. The device according to claim 3, wherein: The first sensor is a head orientation sensor, and the lighting device adjusts the corresponding luminosity of the NIR emitted by the first group of light sources based on the human head orientation detected by the first sensor.

5. The device according to claim 1, wherein: The first attachment feature is selected from the group of attachment features consisting of: a suction cup, an adhesive, a magnet, a screw hole, and a bolt hole.

6. The device according to claim 2, wherein: The first group of light sources is (1) on a first furniture surface, (2) partially in the first furniture surface, or (3) completely in the first furniture surface.

7. The apparatus of claim 1, further comprising a head orientation sensor, wherein: The device adjusts the corresponding luminosity of NIR emitted by the first group of light sources based on the human head orientation detected by the sensor.

8. A device according to claim 1 in the form of a flat screen device comprising a first display surface, wherein: The two or more NIR emitters are configured to emit NIR light that exits from the first display surface.

9. The device according to claim 8, wherein: The flat screen device is a smartphone, a personal data assistant, a tablet computer, a laptop computer, a smart watch, a television or a computer monitor.

10. The device according to claim 1, wherein: Each of the first group of light sources is configured to emit light with a peak wavelength within a first wavelength range, Each of the second group of light sources is configured to emit light with a peak wavelength within a second wavelength range, and The second wavelength range is different from the first wavelength range.

11. The device according to claim 10, wherein: The light emitting device comprises a probe, and the first group of light sources and the second group of light sources are in or on the probe.

12. The device according to claim 1, further comprising at least a first biocompatible element, in, Each of the first group of light sources and each of the second group of light sources are in or on the first biocompatible element, Each of the first group of light sources is configured to emit light with a peak wavelength within a first wavelength range, Each of the second group of light sources is configured to emit light with a peak wavelength within a second wavelength range, and The second wavelength range is different from the first wavelength range.

13. The device according to claim 12, wherein: The first biocompatible element is a sheet.

14. The device according to claim 1, further comprising at least a first light guide and a cladding, in, at least a first light source of the first group of light sources is positioned and oriented relative to the first light guide so that light emitted by the first light source of the first group of light sources enters the first light guide, At least a first light source of the second group of light sources is positioned and oriented relative to the first light guide so that light emitted by the first light source of the second group of light sources enters the first light guide, and The cladding covers one or more portions of the first light guide and prevents light from exiting through the one or more portions.

15. The device according to claim 1, further comprising at least a first light guide, in, at least a first light source of the first group of light sources is positioned and oriented relative to the first light guide so that light emitted by the first light source of the first group of light sources enters the light guide, at least a first light source of the second group of light sources is positioned and oriented relative to the first light guide so that light emitted by the first light source of the second group of light sources enters the light guide, The first light guide is configured to extend at least partially around the body portion, and The first light guide is configured to allow light to exit from at least two light exit areas of the first light guide.

16. The device according to claim 1, further comprising a substrate, in, The substrate is configured to extend at least partially around the body portion, The first group of light sources is located in or on the substrate, and The second group of light sources is located in or on the substrate.

17. The device according to claim 16, wherein: The apparatus is configured to receive a head of a user, and the first and second groups of light sources are oriented so that they deliver light to the head.

18. The device according to claim 16, wherein: The substrate is in the form of a flexible layer, bandage or garment.

19. The apparatus of claim 18, further comprising a plurality of light guides, wherein At least one of the plurality of light guides comprises a first end in or on the substrate and a second end, the second end: a) in said substrate close to at least one light source, or b) is spaced apart from the substrate.

20. The device of claim 1, further comprising a housing comprising a plurality of walls defining an interior space; in, The first set of light sources is positioned and oriented so that light emitted by the first set of light sources is delivered to the interior space, and The second group of light sources is positioned and oriented such that light emitted by the second group of light sources is delivered to the interior space.

21. The device of claim 1, further comprising a sheet and a substrate formed of one or more light guides; in, The first group of light sources is positioned and oriented so that light emitted by the first group of light sources is delivered to at least one of the light guides, and The second group of light sources is positioned and oriented such that light emitted by the second group of light sources is delivered to at least one of the light guides.

22. The device of claim 1, further comprising at least a first cup-shaped housing configured to fit over at least the first body portion; in, At least some of the first group of light sources and the second group of light sources are located on or in the first cup-shaped housing.

23. The device according to claim 11, wherein: The probe is configured to penetrate living biological tissue and / or enter one or more body cavities selected from an incision, a pore, a mouth, any area accessible through the mouth, a nasal cavity, any area accessible through the nasal cavity, an ear, any area accessible through the ear, a rectum, any area accessible through the rectum, a vagina, any area accessible through the vagina, a urethra, and any area accessible through the urethra.

24. The device according to claim 23, wherein: The device further comprises an endoscope, a cannula, a catheter and / or a biosensor.

25. The apparatus of claim 23, further comprising at least one light guide in or on the probe.

26. The device according to claim 1, wherein The device is a medical device, wherein each of the first group of light sources and the second group of light sources is disposed in or on the medical device, and Wherein, the medical device is selected from the group consisting of: a subcutaneous device, a transcutaneous device, a sensor, an oxygen catheter, a drainage device, a drug delivery device, a blood sampling device, an insulin infusion device, an electrical conductor, an endoscope, a tube, a wrap, and an implant.

27. The device of claim 1 for delivering light to the brain, wherein: The two or more visible light emitters include: at least one visible light source that emits light at a wavelength between 640 nm and 680 nm, and at least another visible light source that emits light at a wavelength between 400 nm and 490 nm, wherein the device for delivering light to the scalp, nose, eyes or ears includes a probe or catheter that delivers light below the surface of the skin or inside a body cavity, or the device is in the form of an implant, wherein the device further includes a timer or actuator and a power source.

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