Effect of Transcranial Light Stimulation on the Neurovascular Unit in the Human Brain

Abstract Transcranial light stimulation (tLS) is emerging as a non-invasive approach for enhancing brain function and treating neurological disorders; however, its impact on the human neurovascular unit (NVU) remains poorly understood. Herein, we combined photon transport modeling with multimodal neuroimaging to reveal how light influences vascular and neuronal responses in the human brain. Simulations of photon propagation through transcranial tissue captured key scattering and attenuation patterns, guiding the localization of light effects in vivo. Using simultaneous functional magnetic resonance imaging and arterial spin labeling, we showed that tLS significantly increased blood oxygenation level-dependent signals and cerebral blood flow in the light-affected regions. These hemodynamic changes co-occurred with a reduction in cortical excitability, as revealed by electroencephalographic source reconstruction and transcranial magnetic stimulation-evoked potentials. To probe the underlying mechanism, we incorporated inhibitory neural inputs into the computational NVU model. The model predicted that tLS enhances inhibitory neuronal activity and nitric oxide release, driving vasodilation and elevating metabolic support. These findings revealed that transcranial photons can differentially modulate neuronal and vascular components of the NVU—suppressing excitability while promoting perfusion—thereby suggesting a novel therapeutic avenue for targeting neurovascular dynamics in cognitive and clinical applications.