Cholinergic modulation supports DMN suppression during resting state

Abstract Brain activity during the resting state is widely used to examine brain organization, cognition and alterations in disease states. While it is known that neuromodulation and the state of alertness impact resting-state activity, neural mechanisms behind such modulation of resting-state activity are unknown. In this work, we used a computational model to demonstrate that cholinergic input influences resting-state activity and its functional connectivity through cellular and synaptic modulation. The results from the computational model match closely with experimental work on direct cholinergic modulation of Default Mode Network (DMN) in rodents. We extend those results to the human connectome derived from diffusion-weighted MRI. In the human resting state simulations, an increase in cholinergic input resulted in a brain-wide reduction of functional connectivity. Further, selective cholinergic modulation of DMN closely captured transitions between the baseline resting state and states with suppressed DMN fluctuations associated with attention to external tasks. Our study thus provides insight into potential neural mechanisms for cholinergic neuromodulation on resting state activity and its dynamics. ### Competing Interest Statement The authors have declared no competing interest.