Dose Dependent Effects of Transcranial Photobiomodulation on Blood-Oxygenation-Level-Dependent Power in Major Depressive Disorder.

BACKGROUND: Transcranial photobiomodulation (t-PBM) with near-infrared light stimulates mitochondria and may have antidepressant effects. We evaluated dose-dependent effects of t-PBM on the hemodynamic blood-oxygenation-level-dependent (BOLD) power in major depressive disorder (MDD). METHODS: 31 MDD subjects underwent randomly assigned t-PBM sessions, 1/week, in the MRI scanner, with 1) Sham; 2) High dose: pulse wave, irradiance ∼300 mW/cm2; 3) Medium dose: continuous wave, ∼300 mW/cm2; and 4) Low dose: continuous wave, ∼50 mW/cm2. t-PBM (808 nm) was delivered to the prefrontal cortex, bilaterally. fMRI was recorded at 3T before, during, and after t-PBM. We used mixed-effects linear regression to evaluate changes in BOLD power during stimulation, compared to sham. The analysis was repeated for the middle frontal gyrus (MFG), the prefrontal areas irradiated by t-PBM, and the entire brain cortex. RESULTS: We found similar results in the MFG, the prefrontal cortex directly irradiated, and the entire brain cortex: medium dose t-PBM was associated with a statistically significant increase in BOLD power, whereas low dose t-PBM was associated with a significant decrease in BOLD. There were no significant changes in BOLD power with the high (pulsed) t-PBM dose or with sham. Single administrations of any t-PBM dose did not result in significant changes in depression severity (versus sham). All 3 t-PBM doses were well tolerated. CONCLUSION: The acute effect of t-PBM on the hemodynamic BOLD power is robust, dose-dependent, bidirectional, and extends beyond the areas directly illuminated. These findings may provide a reference for future dose selection and clinical efficacy studies. CLINICALTRIALS: GOV: NCT04366258.