Near-infrared light increases functional connectivity with a non-thermal mechanism

Although techniques for non-invasive brain stimulation are under intense investigation, an approach that has received limited attention is transcranial photobiomodulation (tPBM), the delivery of near-infrared light to the brain with a laser directed at the scalp. Here we employed functional magnetic resonance imaging (fMRI) to measure the Blood-Oxygenation-Level Dependent (BOLD) signal in n = 20 healthy humans while concurrently stimulating their right frontal pole with a near-infrared laser. We failed to detect an evoked BOLD response at illumination. However, functional connectivity with the illuminated region increased by an average of 10% during stimulation, with some connections strengthening by as much as 40%. 23% of connections with the illuminated region experienced a significant acute increase, with the time course of connectivity exhibiting a sharp rise at illumination onset. Brain-wide connectivity increases were also observed, with connections in the stimulated hemisphere showing a significantly larger increase than those in the non-stimulated hemisphere. We subsequently employed MR Thermometry to measure brain temperature during tPBM (separate cohort, n = 20), and found no significant temperature differences between active and sham stimulation. Our findings suggest that near-infrared light synchronizes brain activity with a non-thermal mechanism, underscoring the promise of tPBM as a new technique for stimulating brain function.