Real-time spatial evolution of the fMRI response to photobiomodulation in the healthy human brain

Photobiomodulation (PBM) is a non-invasive therapeutic technique that uses low-level near-infrared light to influence mitochondrial metabolism and stimulate neural function. While PBM is increasingly used to improve cognitive and clinical outcomes, its in vivo physiological mechanisms in humans remain poorly characterized. In this study, we used BOLD-fMRI to investigate and quantify the temporal and spatial dynamics of transcranial PBM-induced brain activity in young, healthy adults, while incorporating multiple stimulation parameters (wavelength, irradiance, frequency) and transcranial delivery sites (right forehead and intranasal). A time-lagged correlation analysis revealed distinct spatiotemporal patterns of positive and negative BOLD responses that evolved over tens of seconds across both cortical surface and subcortical regions during stimulation. Notably, these effects propagated across brain regions that are potentially mediated by functional networks, were dose-dependent, and were modulated by individual skin tone. This work provides the first real-time, whole-brain mapping of PBM-induced hemodynamic changes in humans, offering new insights into dose-response characteristics and delivery-specific dynamics underlying PBM neurophysiology.