Interhemispheric Metabolic Effects of Transcranial Infrared Laser Stimulation of the Prefrontal Cortex

Photobiomodulation is the use of low-power, non-ionizing light to stimulate cellular processes. Transcranial infrared laser stimulation (TILS) is a method for prefrontal photobiomodulation that produces dose-dependent metabolic effects in vivo. However, interhemispheric differences in metabolic responses to unilateral right versus left TILS are unknown. Investigating interhemispheric effects of TILS is important because right-left differences are observed with other forms of transcranial stimulation, including magnetic and electrical stimulation. TILS penetration was first characterized using Monte Carlo simulations of photon propagation in the Colin27 MRI-based brain model. Simulations confirmed that 1%-5% photon penetration was confined unilaterally to the stimulated side of the prefrontal cortex. Eighty-one healthy adults were then randomized to receive unilateral right TILS, unilateral left TILS, or sham stimulation (laser off). Active TILS parameters were selected based on prior studies demonstrating metabolic efficacy (1064 nm continuous wave, 250 mW/cm² irradiance, 440 s exposure, 110 J/cm² fluence, and 1496 J total energy). Bilateral changes in cytochrome-c-oxidase (CCO), oxygenated hemoglobin (HbO), and deoxygenated hemoglobin (HHb) were measured with in vivo spectroscopy before, during, and after unilateral TILS or sham. No adverse effects were reported, and no significant metabolic or hemodynamic changes were observed in the sham condition. Unilateral TILS produced ipsilateral (TILS side) increases in CCO and HbO that were similar regardless of whether the right or left prefrontal cortex was stimulated. In contrast, contralateral (opposite side) metabolic responses differed by stimulation side. Contralateral CCO effects emerged later than ipsilateral effects and were greater in the right hemisphere following TILS to the left. This study is the first to demonstrate an interhemispheric difference in the human brain response to photobiomodulation, specifically contralateral CCO effects. Although ipsilateral metabolic effects were similar for right and left prefrontal stimulation, contralateral responses exhibited hemispheric asymmetry. It is possible that these interhemispheric differences may contribute to the different cognitive and emotional effects of right versus left transcranial photobiomodulation.