Causal evidence for cholinergic stabilization of attractor landscape dynamics.

There is substantial evidence that neuromodulatory systems critically influence brain state dynamics; however, most work has been purely descriptive. Here, we quantify, using data combining local inactivation of the basal forebrain with simultaneous measurement of resting-state fMRI activity in the macaque, the causal role of long-range cholinergic input to the stabilization of brain states in the cerebral cortex. Local inactivation of the nucleus basalis of Meynert (nbM) leads to a decrease in the energy barriers required for an fMRI state transition in cortical ongoing activity. Moreover, the inactivation of particular nbM sub-regions predominantly affects information transfer in cortical regions known to receive direct anatomical projections. We demonstrate these results in a simple neurodynamical model of cholinergic impact on neuronal firing rates and slow hyperpolarizing adaptation currents. We conclude that the cholinergic system plays a critical role in stabilizing macroscale brain state dynamics. [Display omitted] • ACh inhibition impairs brain state transitions while preserving correlations • ACh inhibition leads to flattened energy barriers between brain state attractors • ACh inactivation decreases information flow between targeted cortical regions • Cholinergic model of firing rates and adaptation currents reproduces findings Taylor et al. found that the cholinergic system is important for stabilizing brain state dynamics, which builds upon a body of work emphasizing the importance of the ascending arousal system in modulating global brain state reconfigurations. [ABSTRACT FROM AUTHOR]