Photobiomodulation in the Brain: Low-Level Laser (Light) Therapy in Neurology and Neuroscience

Cover
Photobiomodulation in the Brain: Low-Level Laser (Light) Therapy in Neurology
and Neuroscience
Copyright
Dedication
List of Contributors
Preface
Part I: Basic considerations and in vitro
1 Photobiomodulation therapy and the brain: an innovative tool for therapy and discovery
	1.1 Introduction
		1.1.1 Beyond the structure-function architecture of the human brain
		1.1.2 A bottom-up approach to brain neurosciences
		1.1.3 Modulating the “brain black box” with light
	References
2 Theoretical neuroscience
	2.1 Molecular and cellular neuroscience
		2.1.1 History of neuroscience discovery over the decades
		2.1.2 Molecular techniques in neuroscience research
	2.2 Translational research in neuroscience
	2.3 Approaches to simulations and computational neuroscience
		2.3.1 Neural function simulation
	2.4 Cognition and behavior
	2.5 Neural treatment simulation
	References
3 Photobiomodulation of cultured primary neurons: role of cytochrome c oxidase
	3.1 Introduction
	3.2 Cytochrome c oxidase: a biological mediator of photobiomodulation
	3.3 Effect of photobiomodulaton on primary neurons exposed to tetrodotoxin
	3.4 Equilibrium constants of azide and cyanide with cytochrome c oxidase
	3.5 Effects of photobiomodulation at different wavelengths
	3.6 Optimal regimen of photobiomodulation via light-emitting diode for cultured neurons exposed to cyanide
	3.7 Photobiomodulation pretreatment has added benefits for neurons exposed to cyanide
	3.8 Therapeutic effect of photobiomodulation on primary neurons exposed to MPP+ or rotenone
	3.9 Pretreatment with photobiomodulation is beneficial for neurons exposed to MPP+ or rotenone
	3.10 Conclusions
	Acknowledgments
	References
4 Photobiomodulation on cultured cortical neurons
	4.1 Introduction
	4.2 Dose response in cultured cortical neurons
	4.3 Oxidative stress in cultured cortical neurons
	4.4 Excitotoxicity in cultured cortical neurons
	Conclusion
	References
5 Safety and penetration of light into the brain
	5.1 Introduction
	5.2 Safety
		5.2.1 Animal studies
		5.2.2 Clinical studies
		5.2.3 NeuroThera Effectiveness and Safety Trial clinical trials
	5.3 Light penetration into the brain
	5.4 Mechanism of action
	5.5 Penetration depth
	5.6 Optical properties of tissue
		5.6.1 Light–tissue interactions
		5.6.2 Melanin
		5.6.3 Water
		5.6.4 Hemoglobin
		5.6.5 Optical window
	5.7 Cerebrospinal fluid
		5.7.1 Gray and white brain matter
	5.8 Wavelength
		5.8.1 Animal studies
		5.8.2 Human studies
	5.9 Skull anatomy
		5.9.1 Animal studies
		5.9.2 Human studies
		5.9.3 Monte Carlo modeling
	5.10 Irradiance
	5.11 Coherence
	5.12 Pulsing
	5.13 Tissue storage and processing
	5.14 Conclusion
	References
	Further reading
6 Near-infrared photonic energy penetration—principles and practice
	6.1 Introduction
		6.1.1 Understanding near-infrared light
	6.2 Light interactions with tissue
		6.2.1 Reflection and refraction
		6.2.2 Scattering
		6.2.3 Absorption
		6.2.4 Penetration
		6.2.5 Speckling
	6.3 Infrared light—on a journey to the brain
		6.3.1 Penetration of skin
		6.3.2 Penetration of skull
		6.3.3 Penetration of heterogeneous tissues
		6.3.4 A hairy problem
		6.3.5 Effectively treating the brain
	6.4 Alternative hypotheses to direct near-infrared light energy effects
	6.5 Conclusion
	Acknowledgments
	References
7 Light sources and dosimetry for the brain and whole body
	7.1 Dose
	7.2 Irradiation parameters: wavelength (nm)
	7.3 Penetration
	7.4 Power Watts (W)
	7.5 Beam spot size (cm2)
	7.6 Irradiance (W/cm2)
	7.7 Pulses
	7.8 Coherence
	7.9 Time, energy, and fluence
	7.10 Fluence (energy density) (J/cm2)
	7.11 Irradiation time (seconds)
	7.12 Number of treatments and treatment intervals (hours, days, or weeks)
	7.13 Devices
	References
8 Mechanisms of photobiomodulation in the brain
	8.1 Introduction
	8.2 Molecular mechanisms of photobiomodulation
		8.2.1 Mitochondria and cytochrome c oxidase
		8.2.2 Opsins, flavins, and cryptochromes
		8.2.3 Light-gated ion channels
		8.2.4 Water as a chromophore
	8.3 Mechanisms of photobiomodulation applied to the brain
		8.3.1 Metabolism
		8.3.2 Blood flow
		8.3.3 Neuroprotection
		8.3.4 Oxidative stress
		8.3.5 Antiinflammatory effects
		8.3.6 Neurogenesis
		8.3.7 Synaptogenesis
		8.3.8 Stem cells
		8.3.9 Preconditioning
		8.3.10 Systemic effects
		8.3.11 Laser acupuncture
	8.4 Conclusion
	References
Part II: Studies in animal models
9 Transcranial photobiomodulation for stroke in animal models
	9.1 Introduction
	9.2 Animal models of stroke
		9.2.1 Middle cerebral artery occlusion
		9.2.2 Rabbit small clot embolic stroke model
		9.2.3 Photothrombotic stroke models
	9.3 Photobiomodulation for ischemic stroke in MCAO models
	9.4 Photobiomodulation for ischemic stroke using the RSCEM model
	9.5 Photobiomodulation for ischemic stroke in photothrombotic model
	9.6 Conclusion
	References
10 Photobiomodulation in photothrombotic stroke
	References
11 Remote photobiomodulation as a neuroprotective intervention—harnessing the indirect effects of photobiomodulation
	11.1 Transcranial photobiomodulation
	11.2 Limitations of transcranial photobiomodulation
	11.3 Alternative photobiomodulation treatment modalities
		11.3.1 Intracranial photobiomodulation
		11.3.2 Intranasal photobiomodulation
	11.4 Introducing “remote photobiomodulation”
	11.5 Discovering the indirect effects of photobiomodulation
	11.6 The effects of photobiomodulation on stem cells
	11.7 Remote photobiomodulation as a neuroprotective intervention
		11.7.1 Parkinson’s disease
		11.7.2 Alzheimer’s disease
		11.7.3 Retinopathy
	11.8 The precedent: remote ischemic conditioning
	11.9 Peripheral tissue targets for remote photobiomodulation-induced neuroprotection
	11.10 Mechanisms underlying remote photobiomodulation-induced protection
		11.10.1 Circulating cellular mediators
		11.10.2 Circulating molecular mediators
		11.10.3 Modulation of the microbiome
		11.10.4 Neurogenic signaling
	11.11 Conclusion
	References
12 Photobiomodulation for traumatic brain injury in mouse models
	12.1 Introduction
	12.2 Studies from other laboratories
	12.3 Studies from the Hamblin laboratory
		12.3.1 Closed-head traumatic brain injury study
		12.3.2 Pulsed versus continuous wave photobiomodulation for traumatic brain injury
		12.3.3 Treatment repetition study
		12.3.4 Photobiomodulation increases neurogenesis and neuroprogenitor cells in traumatic brain injury mice
		12.3.5 Photobiomodulation increases BDNF and synaptogenesis in traumatic brain injury mice
		12.3.6 The solution to the problem of 14 daily photobiomodulation treatments
	12.4 Conclusion
	References
13 Photobiomodulation and mitochondria for traumatic brain injury in mouse models
	13.1 Introduction
	13.2 IEX-1 in traumatic brain injury
	13.3 IEX-1 KO mice fail to fully recover from mild traumatic brain injury
	13.4 Histological alteration in IEX-1 KO mice after mild traumatic brain injury
	13.5 Inflammatory responses after mild traumatic brain injury
	13.6 Transcranial photobiomodulation for traumatic brain injury in IEX-1 Knockout Mice
	13.7 Combination of photobiomodulation and metabolic modulation
	13.8 Photobiomodulation assists neurons to survive hypoxia in vitro
	13.9 Photobiomodulation suppresses apoptosis induced by hypoxia
	13.10 Hypoxia accelerates, but photobiomodulation protects against secondary brain injury
	13.11 Mitochondrial functions are additively improved by the combination of photobiomodulation with lactate or pyruvate
	13.12 Photobiomodulation and lactate or pyruvate together fully protect the hippocampal tissue and its function
	13.13 Conclusion
	References
14 Photobiomodulation for depression in animal models
	14.1 Introduction
	14.2 Major depressive disorder
		14.2.1 The extent of the problem
		14.2.2 Pathophysiology of major depressive disorder
			14.2.2.1 Neurotransmitter systems
			14.2.2.2 Cerebral blood flow
			14.2.2.3 Cerebral bioenergetics
			14.2.2.4 Oxidative stress
			14.2.2.5 Neuroinflammation
			14.2.2.6 Neurotrophic factors and neurogenesis
		14.2.3 Animal models of depression and photobiomodulation studies
			14.2.3.1 Pharmacological models
			14.2.3.2 Restraint stress
			14.2.3.3 Chronic mild stress
			14.2.3.4 Transgenic models
			14.2.3.5 Traumatic brain injury-induced depression
			14.2.3.6 Other models
		14.2.4 Behavioral tests used in depression and photobiomodulation studies
			14.2.4.1 Forced swimming test
			14.2.4.2 Tail suspension test
	14.3 Photobiomodulation therapy
		14.3.1 Introduction to photobiomodulation therapy
		14.3.2 Mechanisms of photobiomodulation therapy
			14.3.2.1 Molecular and cellular action mechanisms
			14.3.2.2 Neuroprotective mechanisms
				14.3.2.2.1 Cerebral blood flow
				14.3.2.2.2 Cerebral bioenergetics
				14.3.2.2.3 Neuronal antioxidant defence
				14.3.2.2.4 Neuroinflammation
				14.3.2.2.5 Neurotrophic factors and neurogenesis
				14.3.2.2.6 Cerebral neurotransmitters
		14.3.3 Translational photobiomodulation studies in depression animal models
	14.4 Conclusions and future outlook
	References
15 Transcranial photobiomodulation treats Alzheimer’s disease in amyloid-β protein precursor transgenic mice
	15.1 Introduction
	15.2 Study design
	15.3 Transcranial photobiomodulation improves cognitive performance as measured by Morris Water Maze
	15.4 Transcranial photobiomodulation lowers the amyloid load in brain and reduces levels of Aβ peptides in brain, cerebrosp...
	15.5 Transcranial photobiomodulation reduces inflammation in the brain
	15.6 Transcranial photobiomodulation improves mitochondrial function in the brain
	15.7 Discussion
	15.8 Conclusion
	References
16 Low-level laser therapy to the bone marrow: a new therapeutic approach to neurodegenerative diseases
	Acknowledgment
	References
17 The experimental evidence for photobiomodulation-induced cellular and behavioral changes in animal models of Parkinson’s...
	17.1 Introduction
	17.2 Parkinson’s disease and animal models
	17.3 Photobiomodulation
	17.4 Neuroprotection
	17.5 Gliosis
	17.6 Growth factors
	17.7 Functional activity
	17.8 Behavior
	17.9 Translation to patients
	17.10 Conclusion
	References
	Further reading
18 Effects of near-infrared low-level laser stimulation on neuronal excitability
	18.1 Introductory remarks
	18.2 Neuronal excitability—experimental results
		18.2.1 Effects on peripheral nerves
		18.2.2 Effects on brain
	18.3 Proposed mechanisms
	18.4 Future directions
	Acknowledgment
	References
19 Photobiomodulation for multiple sclerosis in animal models
	19.1 Introduction
	19.2 Experimental autoimmune encephalomyelitis and multiple sclerosis
	19.3 Photobiomodulation therapy for the treatment of experimental autoimmune encephalomyelitis/multiple sclerosis
	19.4 Conclusion and future directions
	References
20 Hepatic encephalopathy and photobiomodulation: experimental models and clinical features
	20.1 Introduction
	20.2 What is hepatic encephalopathy?
		20.2.1 The contribution of ammonia
			20.2.1.1 The glycolytic rate
			20.2.1.2 Lactate overproduction
			20.2.1.3 Crisis in the tricarboxylic acid cycle
			20.2.1.4 Failure in oxidative phosphorylation
		20.2.2 The contribution of oxidative/nitrosative stress
			20.2.2.1 Endotoxemia and inflammation
			20.2.2.2 Oxidative/nitrosative stress
	20.3 Photobiomodulation for hepatic encephalopathy
	Acknowledgment
	References
	Further reading
21 Photobiomodulation in animal models of retinal injury and disease
	21.1 Introduction
	21.2 Methanol intoxication
	21.3 Bright light-induced retinal damage
	21.4 Diabetic retinopathy
	21.5 Retinitis pigmentosa
	21.6 Aging and age-related macular degeneration
	21.7 Retinopathy of prematurity
	21.8 Optic nerve injury
	21.9 Glaucoma
	21.10 Conclusion and future directions
	Acknowledgment
	References
	Further reading
22 Transcranial photobiomodulation therapy for pain: animal models, dosimetry, mechanisms, perspectives
	22.1 Introduction
	22.2 Pain—a major problem for human health
	22.3 Transcranial photobiomodulation therapy—a multidisciplinar solution for pain
	22.4 Photoneuromodulation: dosimetry, mechanisms, and therapeutics in translational research
		22.4.1 Dosimetry
			22.4.1.1 Transcranial photon penetration in animals and humans
			22.4.1.2 Optical properties of brain
		22.4.2 Mechanisms
		22.4.3 Therapeutic effects
		22.4.4 Irradiation of nervous system: peripheral versus central
	22.5 Photoneuromodulation of glutamate receptors, prostatic acid phophatase and adenosine triphosphate
		22.5.1 Behavioral evaluation of pain
		22.5.2 Neurochemical and neurobiological evidences of analgesic effect
	22.6 Future directions of transcranial photobiomodulation therapy for pain
	22.7 Conclusion
	References
Part III: Cinical studies
23 The challenge of effectively translating transcranial near-infrared laser therapy to treat acute ischemic stroke
	23.1 Introduction
	23.2 NeuroThera effectiveness and safety trial (NEST): from transcranial laser therapy efficacy to NEST futility
		23.2.1 NeuroThera effectiveness and safety trial-1
		23.2.2 NeuroThera effectiveness and safety trial-2
		23.2.3 NeuroThera effectiveness and safety trial-3
	23.3 Translational stroke research in the embolic stroke rabbit model
		23.3.1 Preclinical efficacy
	23.4 What went wrong in NeuroThera effectiveness and safety trials?
	23.5 Conclusions and commentary: should transcranial laser therapy be further considered as an approach to treat stroke?
	References
24 Effects of photobiomodulation on traumatic brain injury: proposed clinical assessment
	24.1 Introduction
	24.2 Definition and statistics—traumatic brain injury
	24.3 Developmental aspects
	24.4 Physiological components
	24.5 Psychological manifestations
	24.6 Sociological implications
	24.7 Causation
	24.8 Treatment approaches
	24.9 Most common treatments recommended
	24.10 Results
	24.11 Discussion
	24.12 Future clinical trials for the treatment of traumatic brain injury
	24.13 Conclusion
	References
25 Transcranial, red/near-infrared light-emitting diode therapy for chronic traumatic brain injury and poststroke aphasia: ...
	25.1 Traumatic brain injury
		25.1.1 Introduction to traumatic brain injury
		25.1.2 Sports-related traumatic brain injury
		25.1.3 Traumatic brain injury in soldiers and veterans
		25.1.4 Diffuse axonal injury and white matter abnormalities on magnetic resonance imaging scans
		25.1.5 Development of neurodegenerative disease posttraumatic brain injury
		25.1.6 Functional brain imaging in traumatic brain injury
		25.1.7 Resting-state, functional-connectivity magenetic resonance imaging in traumatic brain injury
		25.1.8 Cognitive dysfunction in traumatic brain injury
		25.1.9 Sleep disturbances in traumatic brain injury
		25.1.10 Pharmacologic treatments for traumatic brain injury
		25.1.11 Cognitive rehabilitation therapies for traumatic brain injury
	25.2 Photobiomodulation for chronic traumatic brain injury
		25.2.1 Transcranial light-emitting diode treatment performed at home, to improve cognition in chronic, mild traumatic brain...
		25.2.2 Transcranial light-emitting diode treatment to improve cognition in chronic, mild traumatic brain injury—open protoc...
		25.2.3 Results
	25.3 Ongoing current studies on photobiomodulation for traumatic brain injury
		25.3.1 Transcranial light-emitting diode treatment to improve cognition and sleep in mild traumatic brain injury
		25.3.2 Intranasal (only) light-emitting diode treatment to improve cognition and sleep
	25.4 Discussion, photobiomodulation for traumatic brain injury
		25.4.1 Executive function, and relationship to resting-state, functional-connectivity magenetic resonance imaging networks ...
		25.4.2 Specific transcranial light-emitting diode placements may affect specific parts of the salience network and default ...
		25.4.3 Verbal learning and memory, and relationship to resting-state, functional-connectivity magenetic resonance imaging (...
		25.4.4 Specific transcranial light-emitting diode placements may affect specific parts of the central executive network in ...
		25.4.5 Depression
		25.4.6 Posttraumatic stress disorder relationship to intrinsic networks, default mode network and salience network
		25.4.7 Weak connections between cortical nodes within intrinsic neural networks
		25.4.8 Mechanisms and cellular effects, post-red/near-infrared transcranial light-emitting diode
	25.5 Photobiomodulation to improve language in chronic aphasia, due to left hemisphere stroke
		25.5.1 Stroke-aphasia
		25.5.2 Importance of specific light-emitting diode placement areas on the scalp to treat aphasia, in chronic stroke
		25.5.3 Bilateral transcranial light-emitting diode treatment method
		25.5.4 Left hemisphere only, transcranial light-emitting diode treatment method
		25.5.5 Results
		25.5.6 Photobiomodulation to treat primary progressive aphasia, a neurodegenerative disease
	25.6 Photobiomodulation for possible chronic traumatic encephalopathy
	25.7 Conclusion
	References
26 Photobiomodulation as a potential therapeutic strategy for improving cognitive and functional outcomes in traumatic brai...
	26.1 Introduction
	26.2 Neuropathology of traumatic brain injury
	26.3 Putative targets of photobiomodulation therapy in traumatic brain injury
	26.4 Treatment parameters and biological targets of photobiomodulation in animal models of traumatic brain injury
	26.5 Effects of photobiomodulation on cognitive performance in animal models of traumatic brain injury
	26.6 Enhancement of cognitive performance in healthy individuals with photobiomodulation treatment
	26.7 Effects of photobiomodulation therapy on cognitive outcomes in traumatic brain injury patients
	26.8 Summary and future directions
	26.9 Conclusion
	References
27 Advanced neuroimaging methods for assessment of low-level light therapy
	27.1 Introduction
	27.2 Known mechanisms of light therapy
	27.3 Preclinical evidence for light therapy
	27.4 Clinical evidence of light therapy efficacy
	27.5 Evidence for transcranial delivery of light
	27.6 Neuroimaging methods
		27.6.1 Computed tomography
		27.6.2 Magnetic resonance imaging
	27.7 Structural imaging
	27.8 Diffusion imaging
	27.9 Perfusion imaging
	27.10 Resting state functional connectivity imaging
	27.11 Functional imaging using hypercapnic challenges
	27.12 Magnetic resonance spectroscopy
	Funding
	References
28 Treatment of traumatic brain injury with near-infrared light
	28.1 Background
		28.1.1 Definition
		28.1.2 Incidence
		28.1.3 Vulnerable populations
			28.1.3.1 Women
			28.1.3.2 Elderly
			28.1.3.3 Children
		28.1.4 Symptoms
	28.2 Diagnostic workup
		28.2.1 Neurological and physical evaluation
		28.2.2 Balance testing
		28.2.3 Dysautonomia
		28.2.4 Cervicogenic headaches
		28.2.5 Questionnaires and cognitive testing
			28.2.5.1 Patient Diary
		28.2.6 Neuroimaging
	28.3 Treatment of traumatic brain injury with near-infrared light therapy
		28.3.1 Overview
		28.3.2 Review of the literature
			28.3.2.1 Preclinical studies
			28.3.2.2 Clinical studies
			28.3.2.3 Our Clinical Experience
	28.4 Conclusion
	Acknowledgment
	References
29 Photobiomodulation: a novel approach to treating Alzheimer’s disease
	29.1 Introduction
	29.2 Pharmacotherapies for Alzheimer’s disease
	29.3 Pathophysiology of Alzheimer’s disease
		29.3.1 Amyloid cascade hypothesis
		29.3.2 Neurofibrillary tangles
		29.3.3 Other protein targets
	29.4 The odds against a monotherapy
	29.5 Mitochondrial cascade hypothesis of Alzheimer’s disease
	29.6 Photobiomodulation and mitochondrial function
	29.7 Photobiomodulation in animal models of Alzheimer’s disease
	29.8 Human clinical studies of photobiomodulation on dementia and Alzheimer’s
		29.8.1 Saltmarche et al. (2017)
		29.8.2 Zomorrodi et al. (2017)
		29.8.3 Ongoing study—Chao (2018)
		29.8.4 Discussion on the clinical studies
	29.9 Key parameters
		29.9.1 The default mode network
		29.9.2 Pulse rate of 40Hz
	29.10 Proving light penetration through electroencephalography measures
	29.11 Electroencephalography as a tool for developing Alzheimer’s disease therapies
	29.12 Pulsed photobiomodulation as a potential treatment modality
	29.13 The future of photobiomodulation as a treatment for Alzheimer’s disease
	References
30 Electroencephalography as the diagnostic adjunct to transcranial photobiomodulation
	30.1 Introduction
	30.2 Electroencephalography
	30.3 Brain waves
		30.3.1 Delta oscillations
		30.3.2 Theta oscillations
		30.3.3 Alpha oscillations
		30.3.4 Beta oscillations
		30.3.5 Gamma oscillations
	30.4 Photobiomodulation as a new noninvasive brain stimulation method
	30.5 The causal link between photobiomodulation and neural oscillations
		30.5.1 Maintaining homeostasis
		30.5.2 Calcium signaling
	30.6 Evidence for transcranial photobiomodulation influences on brain oscillations
	30.7 The potential use of electroencephalography with photobiomodulation for brain disorders
	30.8 Discussion and conclusion
	References
31 Can photobiomodulation enhance brain function in older adults?
	31.1 Frontal lobe deterioration and normal human aging
		31.1.1 Structural and functional deteriorations of the frontal lobe in normal human aging
		31.1.2 Cognitive declines in frontal lobe functioning in normal human aging
		31.1.3 Conventional interventions for improving frontal lobe functioning in normal older adults
	31.2 Photobiomodulation and neuroenhancement
		31.2.1 Mechanisms of action of photobiomodulation
		31.2.2 Photobiomodulation for enhancing brain functions in humans
			31.2.2.1 Healthy humans
			31.2.2.2 Alzheimer disease
			31.2.2.3 Stroke
			31.2.2.4 Traumatic brain injury
			31.2.2.5 Major depressive disorder
	31.3 Photobiomodulation for normal older adults: a potential intervention for the aging brain
	Acknowledgment
	Conflict of interest
	References
	Further reading
32 Noninvasive neurotherapeutic treatment of neurodegeneration: integrating photobiomodulation and neurofeedback training
	32.1 Photobiomodulation and neurotherapy introduction
	32.2 Pathophysiology of neurodegeneration
	32.3 Photobiomodulation therapy
	32.4 Near infrared photobiomodulation decreases synaptic vulnerability to Aβ
	32.5 Early human clinical trials
	32.6 Digit span measures
	32.7 Neuropsychological testing results
	32.8 Treatment of neurodegeneration with directed energy
	32.9 Near infrared spectroscopy assessment of Alzheimer’s
	32.10 Conclusion
	References
	Further reading
33 Transcranial photobiomodulation therapy: observations from four movement disorder patients
	33.1 Introduction
	33.2 Case descriptions
		33.2.1 Progressive supranuclear palsy: Patient FH
		33.2.2 Parkinson’s disease: Patient BS
		33.2.3 Parkinson’s disease: Patient PN
		33.2.4 Parkinson’s disease: Patient MH
	33.3 Discussion
	33.4 Conclusion
	Acknowledgment
	References
34 Cerebral blood flow in the elderly: impact of photobiomodulation
	34.1 Introduction
	34.2 Brain hemodynamics in the elderly
	34.3 Effect of photobiomodulation of the brain in the elderly
	References
	Further reading
35 Transcranial photobiomodulation for major depressive and anxiety disorders and for posttraumatic stress disorder
	35.1 The potential of transcranial photobiomodulation for the anxious and depressed
	35.2 Transcranial photobiomodulation for major depressive disorder
	35.3 Transcranial photobiomodulation for anxiety disorders and for posttraumatic stress disorder
	35.4 Safety and tolerability of transcranial photobiomodulation
	35.5 Dosing transcranial photobiomodulation for mood and anxiety disorders
	35.6 Conclusion
	References
36 Action at a distance: laser acupuncture and the brain
	36.1 Background
		36.1.1 Acupuncture and meridian theory
		36.1.2 Physical properties of meridians and acupoints
		36.1.3 Microsystems
		36.1.4 Acupuncture methods
	36.2 Laser acupuncture
		36.2.1 Potential mechanisms of laser acupuncture
		36.2.2 The deqi question
	36.3 Acupuncture and the brain
		36.3.1 Functional magnetic resonance imaging
	36.4 Laser acupuncture and the brain
		36.4.1 Animal studies
		36.4.2 Laser acupuncture and functional magnetic resonance imaging
		36.4.3 The frequency question
		36.4.4 Laser acupuncture and depression
		36.4.5 Laser acupuncture and cerebral blood flow
		36.4.6 Laser acupuncture and brain oscillations
		36.4.7 Laser acupuncture for stroke and neurorehabilitation
		36.4.8 The wavelength question
	36.5 Conclusion
	References
37 Signature wounds of war: a case study
	37.1 Introduction
	37.2 RESET Therapy
	37.3 Case study
	References
38 Transcatheter intracerebral photobiomodulation in degenerative brain disorders: clinical studies (Part 1)
	38.1 Introduction
	38.2 Materials and methods
		38.2.1 Patient selection criteria
		38.2.2 Patient examination plan
			38.2.2.1 Patient examination results
			38.2.2.2 Patient selection
		38.2.3 Treatment methods
			38.2.3.1 Test group
				38.2.3.1.1 The method of transcatheter intracerebral photobiomodulation
			38.2.3.2 Control group
	38.3 Results
		38.3.1 Test group
			38.3.1.1 Immediate result after transcatheter intracerebral photobiomodulation
			38.3.1.2 Early period (1–6 months) after transcatheter intracerebral photobiomodulation
			38.3.1.3 Long-term (1–7 years) results after transcatheter intracerebral photobiomodulation
		38.3.2 Control group
			38.3.2.1 Early period (1–6 months) after the beginning of conservative treatment
			38.3.2.2 The long-term period (1–5 years) after the beginning of conservative treatment
	38.4 Discussion
	38.5 Conclusion
	38.6 Conflict of interest
	38.7 Funding
	References
39 Transcatheter intracerebral photobiomodulation in ischemic brain disorders: clinical studies (Part 2)
	39.1 Introduction
	39.2 Materials and methods
		39.2.1 Patient selection criteria
		39.2.2 Patient screening plan
		39.2.3 Analysis of patients
		39.2.4 Selection of patients
			39.2.4.1 Group 1
				-Test group 1
				-Control group 1
			39.2.4.2 Group 2
				-Test group 2
				-Control group 2
		39.2.5 Methods of treating patients
			39.2.5.1 Test group 1, Test group 2—Transcatheter intracerebral photobiomodulation was carried out
			39.2.5.2 Control group 1, Control group 2—Conservative treatment was received
		39.2.6 Evaluation of results
	39.3 Results
		39.3.1 Test group 1—Patients with intracerebral atherosclerosis and chronic cerebrovascular insufficiency
			39.3.1.1 Immediate results
			39.3.1.2 Early period (1–6 months) after transcatheter intracerebral photobiomodulation
				Results according to scintigraphy and rheoencephalography
				Results according to computed tomography and magnetic resonance imaging
				Results of assessment of mental and motor functions
			39.3.1.3 Long-term (1–10 years) after transcatheter intracerebral photobiomodulation
				Results according to computed tomography and magnetic resonance imaging
				Results according to multigated angiography data
		39.3.2 Test group 2—patients with intracerebral atherosclerosis and previous ischemic stroke
			39.3.2.1 Immediate results
			39.3.2.2 Early period (1–6 months) after intracerebral photobiomodulation
				Results according to scintigraphy and rheoencephalography
				Results according to computed tomography and magnetic resonance imaging
				Results of assessment of mental and motor functions
			39.3.2.3 Long-term (1–10 years) results after transcatheter intracerebral photobiomodulation
				Results according to computed tomography and magnetic resonance imaging
				Results according to multigated angiography data
		39.3.3 Control group 1—patients with intracerebral atherosclerosis and chronic cerebrovascular insufficiency
			39.3.3.1 Immediate results
			39.3.3.2 Early period (1–6 months) after conservative treatment
				Results according to scintigraphy and rheoencephalography
				Results according to computed tomography and magnetic resonance imaging
				Results of assessment of mental and motor functions
			39.3.3.3 Long-term period (1–10 years) after conservative treatment
				Results according to scintigraphy and rheoencephalography
				Results according to computed tomography and magnetic resonance imaging
		39.3.4 Control Group 2—patients with intracerebral atherosclerosis and previous ischemic stroke
			39.3.4.1 Immediate results
			39.3.4.2 Early period (1–6 months) after conservative treatment
				Results according to scintigraphy and rheoencephalography
				Results according to computed tomography and magnetic resonance imaging
				Results of assessment of mental and motor functions
			39.3.4.3 Long-term period (1–10 years) after the conservative treatment
				Results according to scintigraphy and rheoencephalography
				Results according to computed tomography and magnetic resonance imaging
		39.3.5 Clinical results in the long-term period
	39.4 Discussion
	39.5 Conclusion
	Conflict of interest
	Funding
	References
40 Russian low level laser therapy techniques for brain disorders
	40.1 Introduction
	40.2 Protocol requirements of low level laser therapy procedures in Russia, low level laser therapy techniques
	40.3 Intravenous laser blood illumination
	40.4 Noninvasive laser blood illumination
	40.5 The analysis of the literature on the use of low level laser therapy in patients with various cerebrovascular disorders
	40.6 Indications
	40.7 Contradictions
	References
41 Laser treatment of central nervous system injuries: an update and prospects
	41.1 Introduction
	41.2 Clinical experience
	41.3 Mechanisms of action
	41.4 Appendix—Motor control and the Grimaldi maneuver
	References
42 Photobiomodulation treatment for brain disorders: posttraumatic stress disorder (PTSD) and dementia
	42.1 Introduction (clinical team)
	42.2 Original concussion case
	42.3 Posttraumatic stress disorder evaluation
	42.4 Case studies for posttraumatic stress disorder
		42.4.1 Case studies for dementia
	42.5 Conclusion and future directions
	References
43 What we don’t know and what the future holds
	43.1 Questions, or what we don’t know
	43.2 What are the best diseases and conditions to be treated?
	43.3 How important is light penetration to the brain?
	43.4 What about systemic effects?
	43.5 What is the best way to deliver light?
	43.6 How important is pulsing?
		43.6.1 Pulse parameters and light sources
		43.6.2 Types of pulsed light sources
		43.6.3 Why could pulsing be important in photobiomodulation?
		43.6.4 Effect of pulsing photobiomodulation for the brain
	43.7 How important is the location on the head?
	43.8 How important is the biphasic dose response?
	43.9 What about cognitive enhancement and preconditioning?
	43.10 How does photobiomodulation compare with other noninvasive brain stimulation techniques?
		43.10.1 Transcranial magnetic brain stimulation
		43.10.2 Transcranial direct current stimulation
		43.10.3 Low intensity pulsed ultrasound
	43.11 Could an invasive approach be considered?
	43.12 What does the future hold?
	References
Index
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