What is Photobiomodulation?

Photobiomodulation therapy is defined as the utilization of non-ionizing electromagnetic energy to trigger photochemical changes within cellular structures that are receptive to photons. Mitochondria is particularly receptive to this process. At the cellular level, visible red and near infrared light (NIR) energy are absorbed by mitochondria, which perform the function of producing cellular energy called “ATP”. The key to this entire process is a mitochondrial enzyme called cytochrome oxidase c, a chromophore, which accepts photonic energy of specific wavelengths when functioning below par.

Read a published study (May 2022) using the Vielight Neuro Alpha on the way that living cells, cellular structures, and components such as microtubules and tubulin respond to near-infrared PBM: Link 

What is Photobiology?

Photobiology is the study of the effects of non-ionizing radiation on biological systems. The biological effect varies with the wavelength region of the radiation. The radiation is absorbed by molecules in skin such as DNA, protein or certain drugs. The molecules are changed chemically into products that initiate biochemical responses in the cells.

Biological reaction to light is nothing new, there are numerous examples of light induced photochemical reactions in biological systems. Vitamin D synthesis in our skin is an example of a photochemical reaction. The power density of sunlight is only 105 mW/cm2 yet when ultraviolet B (UVB) rays strikes our skin, it converts a universally present form of cholesterol, 7-dehydrocholesterol to vitamin D3. We normally experience this through our eyes which are obviously photosensitive. Our vision is based upon light hitting our retinas and creating a chemical reaction that allows us to see. Throughout the course of evolution, photons have played a vital role in photo-chemically energizing certain cells. 

What are the Pathways of Photobiomodulation?

  • NO (Nitric Oxide)
  • ROS (Reactive Oxygen Series) → PKD (gene) → IkB (Inhibitor κB) + NF-κB (nuclear factor κB) → NF-κB (nuclear factor κB stimulates gene transcription)
  • ATP (Adenosine Triphosphate) → cAMP (catabolite activator protein) → Jun/Fos (oncogenic transcription factors) → AP-1 (activator protein transcription factor stimulates gene transcription)

What are the Mechanisms of Photobiomodulation?

The current and widely accepted proposal is that low level visible red to near infrared light (NIR) energy is absorbed by mitochondria and converted into ATP for cellular use. In addition, the process creates mild oxidants (ROS), which leads to gene transcription and then to cellular repair and healing. The process also unclogs the chain that has been clogged by nitric oxide (NO).[1] The nitric oxide is then released back into the system. Nitric oxide is a molecule that our body produces to help its 50 trillion cells communicate with each other. This communication happens by transmission of signals throughout the entire body. Additionally, nitric oxide helps to dilate the blood vessels and improve blood circulation.

Photobiomodulation mechanisms

Ref: Original: “Basic Photomedicine”, Ying-Ying Huang, Pawel Mroz and Michael R. Hamblin, Harvard Medical School.
Current design: Vielight Inc.

Parameters

The correct wavelength for the target cells or chromophores must be employed (633-810 nm). However, if the wavelength is incorrect, optimum absorption will not occur. Thus, as the first law of photobiology, the Grotthus-Draper law, states — without absorption there can be no reaction.[2]

The photon intensity, i.e., spectral irradiance or power density (W/cm2), must be adequate, or absorption of the photons will not be sufficient to attain the desired result. However, if the intensity is too high, the photon energy will be transformed to excessive heat in the target tissue, and that is undesirable.[3]

Finally, the dose or fluence must also be adequate (J/cm2). Consequently, if the power density is too low, then prolonging the irradiation time to achieve the ideal energy density, or dose, will, most likely, not give an adequate final result. This happens because the Bunsen-Roscoe law of reciprocity, the 2nd law of photobiology, does not hold true for low incident power densities.[4]

Brain Bioenergetics

Near-infrared light (NIR) stimulates mitochondrial respiration in neurons by donating photons that are absorbed by cytochrome oxidase. This is a bioenergetics process called photoneuromodulation in nervous tissue.[5]The absorption of luminous energy by the enzyme results in increased brain cytochrome oxidase enzymatic activity and oxygen consumption. Since the enzymatic reaction catalyzed by cytochrome oxidase is the reduction of oxygen to water, acceleration of cytochrome oxidase catalytic activity directly causes an increase in cellular oxygen consumption.[6] Increased oxygen consumption by nerve cells is coupled to oxidative phosphorylation. Hence, ATP production increases as a consequence of the metabolic action of near-infrared light. This type of luminous energy can enter brain mitochondria transcranially, and — independently of the electrons derived from food substrates — it can directly photostimulate cytochrome oxidase activity.[7]

References

[1] – “Biphasic Dose Response in Low Level Light Therapy”; Sulbha K. Sharma (PhD), Ying-Ying Huang (MD), James Carroll, Michael R. Hamblin (PhD)

[2, 3, 4] – “Is light-emitting diode phototherapy (LED-LLLT) really effective?”; Won-Serk Kim (PhD, MD), R Glen Calderhead (PhD)

[5, 6, 7] – “Augmentation of cognitive brain functions with transcranial infrared light”; Francisco Gonzalez-Lima (PhD), Douglas W Barrett (MD)

neuron photobiomodulation
photobiomodulation brain

vielightneuro_lightdepthpenetration1

Vielight Neuro - NIR light energy penetration through a human cadaver.

What is brain photobiomodulation?

The brain is the most important and complex human organ. Within every brain cell are mitochondria, which are best understood as energy-producing “powerhouses” or “batteries”. Through biochemical reactions, the mitochondria create fuel for brain cells.

Your brain’s mitochondrial performance can be improved by absorbing light energy (photons) of specific wavelengths. This process is called photobiomodulation (PBM). Scientific research shows our brain’s mitochondria respond positively to light energy within the NIR wavelength range.

When NIR energy from, for example, a Vielight Neuro, is delivered to neuronal mitochondria, it is absorbed by a light-sensitive enzyme called cytochrome c oxidase. This enzyme uses NIR energy to start a series of biochemical reactions that are both beneficial and energizing to the neurons and other brain cells.

Collectively, brain photobiomodulation heals damaged brain cells, improves cerebral blood circulation, reduces inflammation and toxicity, and regenerates damaged brain cells. In a nutshell, NIR light energy to the brain improves efficiency and performance due to better signaling and repaired connectivity between the neurons.

The NIR spectrum of light energy provides the deepest penetration into brain tissues that also result in benefits. We have chosen the NIR wavelength of 810 nm based on the NIR window. To determine the optimal parameters for PBM, research that uses Vielight technology often employ brain imaging and brain signaling techniques.

Penetration of Light Energy

Research and clinical studies show that when NIR light energy has sufficient power density, it is capable of penetrating biological tissue and bone to produce therapeutic outcomes without negative side effects.

What is NIR light energy?

Near infrared light (NIR) energy is part of the electromagnetic spectrum – which are waves (or photons) of the electromagnetic field.It radiates through space and carries electromagnetic radiant energy. Several existing technologies depend on the ability of electromagnetic energy to penetrate solid objects, such as WiFi, mobile data, radar and navigation satellites.

Figure 1 The electromagnetic spectrum

The depth or the power of penetration by light energy depends on the wavelength in the electromagnetic spectrum. Thus, the longer the wavelength, the greater the ability for photons to penetrate an object. NIR light energy is found around the center of the electromagnetic spectrum.

Why near infrared light energy for brain photobiomodulation?

The near infrared (NIR) window is the range in the electromagnetic spectrum where light has a maximum depth of penetration in tissue.[1] This is because the NIR window is defined by the absorption of photons by blood at the shorter wavelengths and by water at the longer wavelengths. NIR light energy also derives the greatest mitochondrial response out of the entire electromagnetic spectrum.

Figure 2 The near infrared window

In particular, visible light (wavelength 400 to 700 nm) is substantially absorbed by hemoglobin and other organic matter. On the other hand, absorption by water increases at wavelengths longer than near infrared light (1000+nm). This implies that wavelengths outside of the near-infrared window cannot penetrate deeply through tissue.

Example: “Fire!” When you hold your hand out to a burning fire you feel heat being emitted by the fire. What is happening? The fire emits infrared radiation, which the water molecules absorb in your skin. Then, this is perceived as heat because the nerves in your skin detect the raised temperature.

Penetration through the skull using NIR LED technology

Several independent published studies support the ability of NIR LED technology to penetrate the skull and irradiate the brain.[2], [3], [4] Lasers are not necessary and harbor inherent unnecessary dangers, due to the nature of coherent light energy – power throttling and overheating tend to occur. The common factor is the wavelength range of 800-830nm, which falls within the body’s optical window.

  1. Smith, Andrew M.; Mancini, Michael C.; Nie, Shuming (2009). “Bioimaging: Second window for in vivo imaging”Nature Nanotechnology4(11): 710–711. doi:1038/nnano.2009.326ISSN 1748-3387PMC 2862008
  2. Jagdeo JR, Adams LE, Brody NI, Siegel DM (2012) Transcranial Red and Near Infrared Light Transmission in a Cadaveric Model. PLOS ONE 7(10): e47460. https://doi.org/10.1371/journal.pone.0047460
  3. Lan Yue and Mark S. Humayun “Monte Carlo analysis of the enhanced transcranial penetration using distributed near-infrared emitter array,” Journal of Biomedical Optics 20(8), 088001 (7 August 2015). https://doi.org/10.1117/1.JBO.20.8.088001
  4. Yuan, Yaoshen & Cassano, Paolo & Pias, Matthew & Fang, Qianqian. (2020). Transcranial photobiomodulation with near-infrared light from childhood to elderliness: simulation of dosimetry. Neurophotonics. 7. 1. 10.1117/1.NPh.7.1.015009.

Mechanisms of Brain Photobiomodulation

mechanisms of photobiomodulation

Brain photobiomodulation (PBM) utilizes red to near-infrared (NIR) photons to stimulate the cytochrome c oxidase enzyme (chromophore/complex IV) of the mitochondrial respiratory chain because this enzyme is receptive to light energy. This outcomes are an increase in ATP synthesis, leading to the generation of more cellular energy. Additionally, photon absorption by ion channels results in release of Ca2+ which leads to the activation of transcription factors and gene expression.

There are several mechanisms associated with promoting physiological change through photobiomodulation therapy (PBMT). The wavelengths primarily used with PBM is within the near-infrared range of the electromagnetic spectrum with a sufficient power density. When hypoxic/impaired cells are irradiated with low level NIR photons, there is increased mitochondrial adenosine tri-phosphate (ATP) production within their mitochondria.[1], [2] Another change is the release of nitric oxide from the hypoxic/impaired cells. Neurons are cells that contain mitochondria and nitric oxide.

In hypoxic neuronal cells, cytochrome-C oxidase (CCO), a membrane-bound protein that serves as the end-point electron acceptor in the cell respiration electron transport chain, becomes inhibited by non-covalent binding of nitric oxide. When exposed to NIR photons, the CCO releases nitric oxide, which then diffuses outs of the cell – increasing local blood flow and vasodilation.[3], [4]

Following initial exposure to the NIR photons, there is a brief burst of reactive oxygen species (ROS) in the neuron cell, and this activates a number of signaling pathways. The ROS leads to activation of redox-sensitive genes, and related transcription factors including NF-κβ.[5], [6] The PBMT stimulates gene expression for cellular proliferation, migration, and the production of anti-inflammatory cytokines and growth factors.[7]

  1. Karu T. Primary and secondary mechanisms of action of visible to near-IR radiation on cells. J Photochem Photobiol B 1999;49:1-17.
  2. Wong-Riley MT, Liang HL, Eells JT, Chance B, Henry MM, Buchmann E, Kane M, Whelan HT. Photobiomodulation directly benefits primary neurons functionally inactivated by toxins: role of cytochrome c oxidase. J Biol Chem 2005;280:4761-4771.
  3. Karu TI, Pyatibrat LV, Afanasyeva NI. Cellular effects of low power laser therapy can be mediated by nitric oxide. Lasers Surg Med 2005;36:307-314.
  4. Huang YY, Chen AC, Carroll JD, Hamblin MR. Biphasic dose response in low level light therapy. Dose Response 2009;7:358-383.
  5. Migliario M, Pittarella P, Fanuli M, Rizzi M, Reno F. Laser-induced osteoblast proliferation is mediated by ROS production. Lasers Med Sci 2014;29:1463-1467.
  6. Avci P, Gupta GK, Clark J, Wikonkal N, Hamblin MR. Low-level laser (light) therapy (LLLT) for treatment of hair loss. Lasers Surg Med 2014;46:144-151.
  7. Huang YY, Gupta A, Vecchio D, de Arce VJ, Huang SF, Xuan W, Hamblin MR. Transcranial low level laser (light) therapy for traumatic brain injury. J Biophotonics 2012;5:827-837.

Therapeutic Outcomes of Brain Photobiomodulation

The literature on brain photobiomodulation is growing rapidly. Currently, there are over 220 published studies on brain photobiomodulation.

Brain photobiomodulation has been shown to increase cerebral perfusion and increase connectivity within the Default Mode Network of patients with Alzheimer’s disease and dementia.[1],[2]

In patients with Parkinson’s disease, measures of mobility, cognition, dynamic balance and fine motor skill y improved (p < 0.05) with PBM treatment for 12 weeks and up to one year.[3]

There is scientific literature that suggests photobiomodulation might be useful for depression/anxiety.[4]

Photobiomodulation has also been shown to induce positive physiological changes for traumatic brain injury.[5]

EEG neural activity can also be influenced by pulsed NIR energy.[6],[7]

We can expect many more research outcomes of PBM featuring the use of Vielight technology in the near future.

  1. 1. Chao LL. Effects of Home Photobiomodulation Treatments on Cognitive and Behavioral Function, Cerebral Perfusion, and Resting-State Functional Connectivity in Patients with Dementia: A Pilot Trial. Photobiomodul Photomed Laser Surg. 2019 Mar;37(3):133-141. doi: 10.1089/photob.2018.4555. Epub 2019 Feb 13. PMID: 31050950.
  2. Saltmarche AE, Naeser MA, Ho KF, Hamblin MR, Lim L. Significant Improvement in Cognition in Mild to Moderately Severe Dementia Cases Treated with Transcranial Plus Intranasal Photobiomodulation: Case Series Report. Photomed Laser Surg. 2017 Aug;35(8):432-441. doi: 10.1089/pho.2016.4227. Epub 2017 Feb 10. PMID: 28186867; PMCID: PMC5568598.
  3. Liebert A, Bicknell B, Laakso EL, Heller G, Jalilitabaei P, Tilley S, Mitrofanis J, Kiat H. Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study. BMC Neurol. 2021 Jul 2;21(1):256. doi: 10.1186/s12883-021-02248-y. PMID: 34215216; PMCID: PMC8249215.
  4. Cassano P, Petrie SR, Mischoulon D, Cusin C, Katnani H, Yeung A, De Taboada L, Archibald A, Bui E, Baer L, Chang T, Chen J, Pedrelli P, Fisher L, Farabaugh A, Hamblin MR, Alpert JE, Fava M, Iosifescu DV. Transcranial Photobiomodulation for the Treatment of Major Depressive Disorder. The ELATED-2 Pilot Trial. Photomed Laser Surg. 2018 Dec;36(12):634-646. doi: 10.1089/pho.2018.4490. Epub 2018 Oct 20. PMID: 30346890; PMCID: PMC7864111.
  5. Chao LL, Barlow C, Karimpoor M and Lim L (2020) Changes in Brain Function and Structure After Self-Administered Home Photobiomodulation Treatment in a Concussion Case. Front. Neurol. 11:952. doi: 10.3389/fneur.2020.00952
  6. Hala El Khoury, John Mitrofanis, Luke A Henderson, Exploring the Effects of Near Infrared Light on Resting and Evoked Brain Activity in Humans Using Magnetic Resonance Imaging,Neuroscience,Volume 422,2019, ISSN 0306-4522, https://doi.org/10.1016/j.neuroscience.2019.10.037.

Published Brain Photobiomodulation research

Alzheimer’s Disease

Effects of Home Photobiomodulation Treatments on Cognitive and Behavioral Function and Resting-State Functional Connectivity in Patients with Dementia: A Pilot Trial
Institutes – University of California San Francisco & the Veterans Affairs USA

[ Published Study Link (Photomedicine and Laser Surgery, 2018) ]

Significant Improvement in Cognition in Mild to Moderately Severe Dementia Cases Treated with Transcranial Plus Intranasal Photobiomodulation: Case Series Report
Co-authoring institutes – Harvard Medical School, Boston University School of Medicine

[ Published Study (Photomedicine and Laser Surgery, 2015) ]

Parkinson’s Disease

Improvements in clinical signs of Parkinson’s disease using photobiomodulation: A prospective proof-of-concept study
Institutes – University of Sydney, University of New South Wales, Griffith University

[ Published Study Link (Liebert, 2021) ]

Traumatic Brain Injury / Concussion

Changes in Brain Function and Structure After Self-Administered Home Photobiomodulation Treatment in a Concussion Case
Institutes – VA Advanced Imaging Research Center, San Francisco VA Health Care System, Departments of Radiology & Biomedical Imaging and Psychiatry & Behavioral Sciences, University of California, San Francisco

[ Published Study Link (Frontiers, Neurology, 2020) | National Center for Biotechnology Information Link ]

Brain EEG Modulation

Pulsed Near Infrared Transcranial and Intranasal Photobiomodulation Significantly Modulates Neural Oscillations: a pilot exploratory study
Institutes – Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, Canada

[ Published Study Link (Nature, Scientific Reports, 2019) | National Center for Biotechnology Information Link ]

Exploring the Effects of Near Infrared Light on Resting and Evoked Brain Activity in Humans Using Magnetic Resonance Imaging
Institutes – University of Sydney

[ Published Study Link (Elsevier, December 2019) ]

Modulation of cortical oscillations using 10hz near-infrared transcranial and intranasal photobiomodulation: a randomized sham-controlled crossover study

[ Abstract Text Link (Brain Stimulation Journal, December 2021) ]

PTSD and Gulf War Illness

Improvements in Gulf War Illness Symptoms After Near-Infrared Transcranial and Intranasal Photobiomodulation: Two Case Reports
Institutes – University of California San Francisco & the Veterans Affairs USA

[ Published Study Link (Military Medicine, 184, 9/10:5, 2019) ]


Penetration

Selective photobiomodulation for emotion regulation: penetration study
Harvard Psychiatry Department, Harvard Medical School : Link ]

Red and NIR light dosimetry in the human deep brain
Institute of Chemical Sciences and Engineering, Switzerland : Link 1 ]

Photon Penetration Depth in Human Brains
The University of Southern California : Link ]

Monte Carlo analysis of the enhanced transcranial penetration using distributed near-infrared emitter array.
Institute of Biomedical Engineering, Chinese Academy of Medical Science : Link ]

Transcranial Red and Near Infrared Light Penetration in Cadavers
State University of New York Downstate Medical Center : Link ]

Quantitative analysis of transcranial and intraparenchymal light penetration in human cadaver brain tissue
Oregon Health and Science University : Link 1 ]

Cellular Effects

Photobiomodulation Directly Benefits Primary Neurons Functionally Inactivated by Toxins
Medical College of Wisconsin : [ Link ]

Neuroprotective effects of photobiomodulation : Evidence from assembly/disassembly of the Cytoskeleton
University of Sydney : [ Link ]

Photobiomodulation – mitochondrial ROS generation and calcium increase in neuronal synapses.

Novel Methods

A novel method of applying NIR light intracranially, impact on dopaminergic cell survival
University of Sydney, CEA-Leti : [ Link ]

Lin-Kou Medical Center, Taiwan : [ Link ]

Infrared neural stimulation and functional recruitment of the peripheral Nerve
Department of Biomedical Engineering, Case Western Reserve University : [ Link ]

Cognition

Effect of Transcranial Low-Level Light Therapy vs Sham Therapy Among Patients With Moderate Traumatic Brain Injury
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston : [ Link ]

Brain Photobiomodulation Therapy: a Narrative Review
Department of Medical Physics, Tabriz University of Medical Sciences : [ Link ]

Psychological benefits with near infrared light to the forehead: a pilot study on depression
The Department of Psychiatry, Harvard Medical School and the Laboratory for Psychiatric Biostatistics, McLean Hospital : [ Link ]

Cognitive Enhancement by Transcranial Photobiomodulation Is Associated With Cerebrovascular Oxygenation of the Prefrontal Cortex
Department of Psychology, Institute for Neuroscience, University of Texas : [ Link ]

Mitochondrial Dysfunction-Near-Infrared Photobiomodulation as a Potential Therapeutic Strategy
Department of Research, National Neuroscience Institute, Singapore : [ Link ]

Transcranial Photobiomodulation For The Management Of Depression: Current Perspectives
Department of Psychiatry, NYU Langone School of Medicine, New York, NY, USA : [ Link ]

Increased Functional Connectivity Within Intrinsic Neural Networks in Chronic Stroke Following Treatment With Red/Near-Infrared Transcranial Photobiomodulation
Boston University School of Medicine, Harvard Medical School : [ Link ]

Review of transcranial photobiomodulation for major depressive disorder: targeting brain metabolism, inflammation, oxidative stress, and neurogenesis
Wellman Center for Photomedicine, Massachusetts General Hospital : [ Link ]

Shining light on the head : Photobiomodulation for brain disorders
Wellman Center for Photomedicine, Massachusetts General Hospital : [ Link ]

Improved cognitive function after transcranial, light-emitting diode treatments in chronic, traumatic brain injury: two case reports
Boston University, School of Medicine : [ Link ]

Augmentation of cognitive brain functions with transcranial lasers
Department of Psychology and Institute for Neuroscience, University of Texas : Link ]

Neurological and psychological applications of transcranial lasers and LEDs
Department of Neurology and Neurotherapeutics, University of Texas : Link ]