How reliable is cerebral blood flow to map changes in neuronal activity?

Neuroimaging techniques, such as functional MRI, map brain activity through hemodynamic-based signals, and are invaluable diagnostic tools in several neurological disorders such as stroke and dementia. Hemodynamic signals are normally precisely related to the underlying neuronal activity through neurovascular coupling mechanisms that ensure the supply of blood, glucose and oxygen to neurons at work. The knowledge of neurovascular coupling has greatly advanced over the last 30 years, it involves multifaceted interactions between excitatory and inhibitory neurons, astrocytes, and the microvessels. While the tight relationship between blood flow and neuronal activity forms a fundamental brain function, whether neurovascular coupling mechanisms are reliable across physiological and pathological conditions has been questioned. In this review, we interrogate the relationship between blood flow and neuronal activity during activation of different brain pathways: a sensory stimulation driven by glutamate, and stimulation of neuromodulatory pathways driven by acetylcholine or noradrenaline, and we compare the underlying neurovascular coupling mechanisms. We further question if neurovascular coupling mechanisms are affected by changing brain states, as seen in behavioral conditions of sleep, wakefulness, attention and in pathological conditions. Finally, we provide a short overview of how alterations of the brain vasculature could compromise the reliability of neurovascular coupling. Overall, while neurovascular coupling requires activation of common signalling pathways, alternate unique cascades exist depending on the activated pathways. Further studies are needed to fully elucidate the alterations in neurovascular coupling across brain states and pathological conditions.