Resting state functional connectivity: its physiological basis and application in neuropharmacology

Brain structures do not work in isolation; they work in concert to produce sensory perception, motivation and behavior. Systems-level network activity can be investigated by resting state magnetic resonance imaging (rsMRI), an emerging neuroimaging technique that assesses the synchrony of the brain's ongoing spontaneous activity. Converging evidence reveals that rsMRI is able to consistently identify distinct spatiotemporal patterns of large-scale brain networks. Dysregulation within and between these networks has been implicated in a number of neurodegenerative and neuropsychiatric disorders, including Alzheimer's disease and drug addiction. Despite wide application of this approach in systems neuroscience, the physiological basis of these fluctuations remains incompletely understood. Here we review physiological studies in electrical, metabolic and hemodynamic fluctuations that are most pertinent to the rsMRI signal. We also review recent applications to neuropharmacology - specifically drug effects on resting state fluctuations. We speculate that the mechanisms governing spontaneous fluctuations in regional oxygenation availability likely give rise to the observed rsMRI signal. We conclude by identifying several open questions surrounding this technique. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'.