The Basal Forebrain Regulates Global Resting-State fMRI Fluctuations

Patterns of spontaneous brain activity, typically measured in humans at rest with fMRI, are used routinely to assess the brain’s functional organization. The mechanisms that generate and coordinate the underlying neural fluctuations are largely unknown. Here we investigate the hypothesis that the nucleus basalis of Meynert (NBM), the principal source of widespread cholinergic and GABAergic projections to the cortex, contributes critically to such activity. We reversibly inactivated two distinct sites of the NBM in macaques while measuring fMRI activity across the brain. We found that inactivation led to strong, regionalized suppression of shared or “global” signal components of cortical fluctuations ipsilateral to the injection. At the same time, the commonly studied resting-state networks retained their spatial structure under this suppression. The results indicate that the NBM contributes selectively to the global component of functional connectivity but plays little if any role in the specific correlations that define resting-state networks. •Inactivation of the nucleus basalis decreased ipsilateral global fMRI fluctuations•Reduction of global signal was strongest in known cortical projection targets•Nucleus basalis inactivation had minimal effect on resting-state fMRI networks•Effects of inactivation on fMRI were most pronounced during periods of low arousal Turchi et al. demonstrate that the basal forebrain, a major source of modulatory projections to the cerebral cortex, controls the level of broadly shared (“global”) spontaneous fluctuations without altering the spatial structure of resting-state networks.