Cholinergic neuromodulation of inhibitory interneurons facilitates functional integration in whole-brain models

Abstract

Segregation and integration are two fundamental principles of brain structural and functional organization. Neuroimaging studies have shown that the brain transits between different functionally segregated and integrated states, and neuromodulatory systems have been proposed as key to facilitate these transitions. Although computational models have reproduced the effect of neuromodulation at the whole-brain level, the role of local inhibitory circuits and their cholinergic modulation has not been studied. In this article, we consider a Jansen & Rit whole-brain model in a network interconnected using a human connectome, and study the influence of the cholinergic and noradrenergic neuromodulatory systems on the segregation/integration balance. In our model, a newly introduced local inhibitory feedback enables the integration of whole-brain activity, and its modulation interacts with the other neuromodulatory influences to facilitate the transit between different functional states. Our work proposes a new possible mechanism behind segregation and integration in the brain.

Structural connections between the noradrenergic and cholinergic system shape the dynamics of functional brain networks

“…The flexibility of this approach offers a number of exciting opportunities for progress on this front. For instance, a recent study included an ‘inhibitory gain’ term to an existing computational model to mimic the effects of the cholinergic system – this allowed the control of both inhibitory and disinhibitory interneurons, which in turn controlled feedback excitation in a manner that provided tighter control over the balance between segregation and integration ( Coronel-Oliveros et al, 2020 ). It is also highly likely that neuromodulatory transmitters other than the cholinergic and noradrenergic systems are responsible for nuanced alterations in dynamic network reconfigurations.…”