Neuromodulation of Cerebral Blood Flow: A Physiological Mechanism and Methodological Review of Neurovascular Coupling

Neurovascular coupling (NVC) refers to the dynamic regulation of cerebral blood flow via neuronal activity, a mechanism crucial for maintaining normal brain function. This review elucidates the intricate physiological mechanisms underlying NVC, emphasizing the coordinated roles of neurons, glial cells, and vascular cells in mediating activity-induced changes in blood flow. We examine how NVC is impaired in neurological disorders such as Alzheimer's disease and stroke, where the dysfunction of this coupling contributes to neurodegeneration and neurological deficits. A broad range of techniques for assessing NVC is discussed-encompassing the established modalities like transcranial Doppler, near-infrared spectroscopy, and functional magnetic resonance imaging (fMRI), as well as emerging technologies such as functional ultrasound imaging and miniaturized endoscopy that enable high-resolution monitoring in deep brain regions. We also highlight the computational modeling approaches for simulating NVC dynamics and identify the novel biomarkers of NVC dysfunction with potential utility in early diagnosis. Finally, emerging translational applications-including neuromodulation techniques and targeted pharmacological interventions-are explored as means to restore normal neurovascular function. These advancements underscore the clinical significance of NVC research, paving the way for improved diagnostic tools and therapeutic strategies in neurological disorders.