Mathew, A.; Van Lankveld, H.; Zhong, X. Z.; Chen, J. X.; Chen, J. J.

Transcranial photobiomodulation (tPBM) is a non-invasive technique that harnesses near-infrared (NIR) light to modulate brain activity. Despite growing evidence of its cognitive and electrophysiological benefits, the in vivo mechanisms and dose-response characteristics of tPBM remain underexplored, especially in relation to differences in skin pigmentation. Our study investigates real-time EEG responses to pulsed tPBM in 46 healthy young adults across a wide range of skin tones, quantified using individual topography angle (ITA) metrics. Participants received stimulation to the right prefrontal cortex using varied combinations of wavelength (808 vs. 1064 nm), frequency (10 Hz vs. 40 Hz), and irradiance (100, 150, and 200 mW/cm2). EEG spectral power and sample entropy were assessed across five canonical frequency bands (delta, theta, alpha, beta, and low gamma) during and after stimulation. Our findings revealed frequency- and region-specific neuromodulation, with 1064 nm and 40 Hz parameters consistently enhancing widespread beta and gamma power, and 808 nm at 40 Hz yielding the most robust alpha power increases, contrary to the initial hypothesis that 10 Hz stimulation would elicit greater alpha enhancement. Entropy changes were more transient and stimulus-bound, while power effects, particularly in alpha and gamma bands, showed sustained post-stimulation persistence. Notably, lighter skin tones and higher irradiance were consistently associated with greater EEG modulation, highlighting the significant impact of melanin-related light attenuation on PBM efficacy. These results underscore the importance of individualized stimulation protocols and establish EEG as a powerful tool for mapping dose- and biophysical-dependent effects of pulsed tPBM in humans.