Intranasal photobiomodulation: an energy efficient paradigm for cortical and subcortical stimulation

Previous studies have shown the hemodynamic response to transcranial photobiomodulation (tPBM) in localized cortical regions during and after forehead irradiation. However, it is unclear if tPBM can reach deeper regions such as subcortical tissue. It is also unclear whether the manner of regional neurovascular coupling predominantly studied using tPBM extends to all brain regions. As an alternative to forehead delivery, intranasal PBM (iPBM) uses the pathway of the cribriform plate, which is thin and directly leads to the orbitofrontal cortex, rather than the prefrontal cortex in the case of forehead PBM. Thus, it is possible that iPBM can stimulate the brain more efficiently (i.e. with less power). In this study, healthy young adults underwent different iPBM protocols differing in wavelength, frequency and irradiance. We utilized functional magnetic resonance imaging (fMRI) to quantify regional blood oxygenation (BOLD) and perfusion. We further model the neurovascular interactions underlying the fMRI response. We uncovered three distinct temporal signatures, varying by brain region. Specifically, a significant response in the thalamus was observed, with a time-locked BOLD response. Overall, iPBM was found to be associated with much higher efficiency at eliciting BOLD fMRI responses than its forehead (tPBM) counterpart. Lastly, in addition to the expected dose dependence, there were extensive sex differences in the fMRI response to iPBM, surpassing those observed for tPBM. Collectively, these findings highlight the feasibility and efficacy of iPBM and establish a foundation for personalizing PBM protocols for optimal outcomes.