Brain photobiomodulation (PBM) therapy using red to near-infrared (NIR) light is an innovative treatment for a wide range of neurological and psychological conditions. Red/NIR light is able to stimulate complex IV of the mitochondrial respiratory chain (cytochrome c oxidase) and increase ATP synthesis. Moreover, light absorption by ion channels results in release of Ca2+and leads to activation of transcription factors and gene expression. Brain PBM therapy enhances the metabolic capacity of neurons and stimulates anti-inflammatory, anti-apoptotic, and antioxidant responses, as well as neurogenesis and synaptogenesis. Its therapeutic role in disorders such as dementia and Parkinson’s disease, as well as to treat stroke, brain trauma, and depression has gained increasing interest.
In the transcranial PBM approach, delivering a sufficient dose to achieve optimal stimulation is challenging due to exponential attenuation of light penetration in tissue. Alternative approaches such as intracranial and intranasal light delivery methods have been suggested to overcome this limitation. This article reviews the state-of-the-art preclinical and clinical evidence regarding the efficacy of brain PBM therapy.
Over the past two decades, brain photobiomodulation (PBM) therapy has been introduced as an innovative modality for the stimulation of neural activity in order to improve brain function. This light-based technique involves exposure of neural tissue to a low fluence of light (ranging from < 1 to >20 J/cm2, and at wavelengths ranging from red to near-infrared (NIR) (600 to 1100 nm) via various light delivery methods . The safety and optimal treatment parameters of brain PBM therapy such as wavelength, fluence, power density, number of repetitions, duration of treatment, and the mode of light delivery (continuous
or pulsed) have been variously investigated in preclinical studies [2–5]. The first in vivo evidence of the neurotherapeutic effects of PBM therapy were achieved in the rabbit embolic stroke model to test its ability to prevent damage or repair damage to the brain occurring after a stroke . The neuroprotective effects of laser and light emitting diodes (LED) in diverse neurological conditions such as traumatic brain injury (TBI) , ischemic stroke (IS) , Alzheimer’s disease (AD) , Parkinson’s disease (PD) , and psychological disorders such as depression and anxiety [11,12], as well as age-related cognitive decline [13,14] have been also shown.
The beneficial effects of PBM are mainly thought to result from the photostimulation of the mitochondrial electron transfer chain (ETC). When PBM is applied at optimum fluences (energy densities) and wavelengths, it produces therapeutic effects in the target organs without causing any adverse effects [15,16]. PBM therapy increases cerebral blood flow (CBF) [17–19], augments brain energy metabolism [17,20,21] and increases antioxidant defenses . Moreover, its ability to promote neuronal protection and survival is mediated through modulation of anti-apoptotic and pro-apoptotic mediators [22,23] and inflammatory signaling molecules [24,25] as well as the stimulation of neurotrophic factors [4,26,27].
Medically speaking a wide range of neurological and psychological disorders affects various cerebral structures. Recent clinical brain PBM therapy studies have been focused on conditions such as AD, PD, TBI and ischemic stroke as well as MDD. However there is also a growing interest for application of this non-invasive modality in perfectly healthy individuals to improve their cognitive abilities (cognitive enhancement)
Despite the existence of several animal studies, there have only been a few studies on the efficacy of PBM therapy in AD and dementia patients. Regarding these human studies, significant improvements in sleep quality, mood states, EEG patterns as well as improved cognitive function including memory and attention, have been obtained as a consequence of NIR PBM therapy [71,195]. Besides, red laser delivered via an arterial catheter leading into the brain gave improvement of CBF in AD patient, and also resulted in a remarkable reduction of dementia scores .
To date, the majority of the clinical investigations revealed positive impacts of transcranial PBM therapy in conditions such as TBI, stroke and depression, in which the target area was in the cortical regions of the brain. On the other hand, PD pathogenesis is linked to abnormalities in the SNc, a midbrain structure that is located at a depth 80–100 mm from the coronal suture, below the dura. Studies have suggested that light in the NIR region may not penetrate the human brain deeper than 20 mm from the cortical surface . This is considered to be a clear limitation in the application of transcranial PBM therapy in human PD. However, in the only (non-controlled, non-randomized) study in PD patients, improved motor and cognitive functions has been reported following 2 weeks of transcranial PBM therapy .
So far, although the majority of animal studies have been conducted on acute TBI models, by contrast the majority of clinical studies have been conducted on chronic TBI patients. It is quite common for humans who recover from a moderate or severe head injury to suffer from a wide variety of long-lasting symptoms including cognitive impairment (eg, poor memory, impaired executive function, and difficulties concentrating), headaches, disturbed sleep, and depression. In the early open studies in TBI, transcranial LED therapy (633/870 nm) improved self-awareness, self-regulation in social functioning and sleep quality [30,33]. The higher fluence of NIR laser resulted in greater clinical efficacy such as diminished signs of headache and improved sleep quality as well as improved cognitive and mood states in TBI patients . In addition, improving the alertness and awareness in TBI patients with severe disorders of consciousness was achieved following irradiation at 785 nm, a somewhat uncommon wavelength for transcranial PBM therapy
To date, three clinical trials, called “Neurothera Effectiveness and Safety Trials” (NEST-1 , NEST-2 , and NEST-3 ) have been carried out in acute stroke patients. Although the phase I and II studies showed both the safety and effectiveness of PBM therapy using 808 nm laser (applied within 24 h of stroke onset), phase III trials were disappointing and were terminated for futility at an interim analysis stage. Besides these, an effort has been made in occasional studies to show neuroprotective or neuroreparative effects of PBM therapy in chronic stroke patients via transcranial  and multiple area  irradiation methods.
The development of effective and sustainable treatment modalities for major depression has been a global aim for decades. To date, studies on antidepressant effects of PBM therapy have had relatively short follow-up periods and could be divided into two types of studies, patients with MDD [11,202,203] and TBI patients with comorbid depression [30,33,61]. The first study in MDD patients showed that a single-session of LED therapy alleviated depression and anxiety symptoms
|Name||Brain Photobiomodulation Machine|
|LED Wavelength||810 nm|
|Power(total helmet)||15 W|
|Power(one LED)||60 mW|