Dose dependence and neurovascular mechanisms of the fMRI response to pulsed photobiomodulation in humans

BackgroundTranscranial photobiomodulation (tPBM) utilizes near-infrared light to penetrate the skull to stimulate neural tissue. However, the in vivo physiological response and the factors influencing this response in the human brain have yet to be understood. MethodsIn this study, we utilize functional magnetic resonance imaging (fMRI) to evaluate the effect of tPBM on the blood-oxygenation (BOLD) and cerebral blood flow (CBF), while varying stimulation parameters such as wavelength, irradiance, and frequency. We further examine the influence of skin tone and sex. We further model the neurovascular interactions underlying the response. ResultsOur results show that the fMRI responses to tPBM is not restrained to the site of irradiation, but quickly spreads to distal sites. Certain regions display an fMRI response sustained after tPBM cessation. Importantly, the responses are dependent on biological and stimulation parameters. Lastly, biophysical modeling revealed a consistent neurovascular coupling-like behaviour underlying these responses. ConclusionEmpirical characterizations of dose dependence are critically important to brain stimulation methods in general but have yet to be demonstrated in most cases. This is the first tPBM study to do just that, establishing the foundation for precision medicine using tPBM, and sets a valuable precedent for the field of brain stimulation.