Transcranial Photobiomodulation for Neuromodulation of Brain Disorders: A Perspective

Photobiomodulation (PBM) uses light to modulate biological activity. Because red and near-infrared wavelengths penetrate the skin and skull, PBM can be applied transcranially (tPBM) to noninvasively modulate brain activity, offering therapeutic potential for neurologic, psychiatric, neurodevelopmental, neurodegenerative, and neuroimmunologic disorders, and for cognitive enhancement.

A scoping review is performed integrating literature on tPBM in humans, excluding indications for which only preclinical data exist.

tPBM can be delivered through the scalp, nose, oral cavity, or external ear canal, in continuous or pulsed modes, with varying wavelengths and doses. It exhibits a biphasic dose-response, meaning both under- and overstimulation are possible. tPBM directly enhances cellular energy metabolism, oxygenation, and neuroprotection by stimulating mitochondria, promoting repair, reducing apoptosis, and modulating neuroinflammation. It supports neurogenesis, synaptogenesis, angiogenesis, and microtubule plasticity, and activates the glymphatic clearance system. Additional effects include transient receptor potential vanilloid 1 calcium channel modulation, intercellular mitochondrial transfer, and immune cell recruitment. Preclinical studies indicate benefits in epilepsy, hypoxic-ischemic lesions, intraventricular hemorrhage, and posttraumatic stress disorder, whereas clinical studies cover stroke, traumatic brain injury, chronic traumatic encephalopathy, autism spectrum disorder, attention-deficit/hyperactivity disorder, Down syndrome, Alzheimer's and Parkinson's diseases, anxiety, depression, insomnia, sexual dysfunction, and multiple sclerosis.

Optimal tPBM outcomes may depend on multitarget, multiwavelength approaches, and pulsed delivery, likely owing to complementary mechanisms and prevention of excessive reactive oxygen species production. Understanding the full range of illumination parameters is essential to develop personalized protocols. Future research should determine whether tPBM can serve as a standalone therapy or as part of multimodal interventions including pharmacology, psychotherapy, or other neuromodulation techniques.