Photobiomodulation for the Brain: A Systematic Review

Background and Aim : Photobiomodulation (PBM) therapy is a developing therapeutic approach in which irradiation with low levels of red to near-infrared light (600 to 1100 nm) delivered from lasers or light-emitting diodes (LEDs) modulates cellular functions. As the proposed underlying mechanism of action, the absorption of red/near-infrared lights by CCO causes a redox change in the enzyme, leading to mitochondrial stimulation and increased ATP production. Evidence continues to accumulate regarding the effectiveness of PBM therapy in neurological and neuropsychiatric disorders as well as boosting brain function in healthy individuals.Methods : The present study systematically reviewed published pre-clinical and clinical articles regarding PBM of neuronal cell cultures or the brain in animals and humans. We searched Web of Science and PubMed databases from 1967 to September 2019 using 233 relevant keywords. Results were reduced to peer-reviewed original articles.Results : The initial search yielded more than 16,000 unique articles, of which 259 were eligible for inclusion. Of these, 59 were in vitro, 139 were in vivo, and 61 were original clinical articles. The specific wavelengths of 600-670 nm, 800-870 nm, 980 nm, and 1064-1068 nm appeared to be superior for brain PBM. Fluence values ranging from 0.1 to 15 J/cm2 were found to be effective for PBM of neuronal cells. Fluence levels measured at the cortex ranging from 1 to 8 J/cm2 were effective for the treatment of various animal models of brain disorders. For human studies, scalp fluences ranged from 10 to 30 J/cm2 for neurological disorders, 13 to 84 J/cm2 for neuropsychiatric disorders, and 15 to 60 J/cm2 for healthy individuals, depending on the severity of the pathology, depth of the target brain tissue, and the desired treatment outcomes. Brain PBM therapy could augment cerebral bioenergetics and blood flow, and could act as a neuroprotective approach via amelioration of neuronal oxidative stress, apoptosis, and neuroinflammation, and via stimulation of neurogenesis and synaptogenesis. Collectively, brain PBM could be promising in patients with (1) stroke by improving clinical metrics (NIHSS and Glasgow Outcome scales); (2) chronic traumatic brain injury by improving social functioning, self-awareness, sleep quality as well as mood and cognitive function; (3) major depression by alleviating depressive and anxiety symptoms (Hamilton scales) and sexual dysfunction; (4) dementia by improving cognitive function such as learning, memory and attention (MoCA and MMSE scales); and (5) Parkinson’s disease by improving motor and cognitive functions. The potential benefits of this modality have also been shown in patients with bipolar disorder, consciousness disorders, autism, Down syndrome, multiple sclerosis, and amyotrophic lateral sclerosis. Furthermore, PBM can enhance higher-order cortical functions including prefrontal rule-based learning, short-term memory, and sustained attention as well as executive functions in healthy individuals.Conclusion : Although the number of controlled human studies has not yet reached a sufficient weight to support mainstream clinical acceptance, the majority of reports that have appeared so far support its neuroprotective effects and tolerability and safety. It is possible that brain PBM therapy will play an even larger role in the neurorehabilitation field in the future if controlled clinical trials now being performed are successful.

Keywords:

Photobiomodulation , LEDs , Near-infrared light , Brain function , Neurological disorders , Psychiatric disorders