Coronel-Oliveros, CarlosCofré, RodrigoOrio, Patricio2022-11-302022-11-302021Coronel-Oliveros C, Cofre ́ R, Orio P (2021) Cholinergic neuromodulation of inhibitory interneurons facilitates functional integration in whole-brain models. PLoS Comput Biol 17(2): e1008737. https://doi.org/10.1371/journal. pcbi.1008737http://repositoriobibliotecas.uv.cl/handle/uvscl/7298Segregation 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 whole-brain computational models have reproduced this neuromodulatory effect, 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, we introduce a local inhibitory feedback as a plausible biophysical mechanism that enables the integration of whole-brain activity, and that interacts with the other neuromodulatory influences to facilitate the transition between different functional segregation/integration regimes in the brain.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.NEURONACHOLINERGICSNEUROMODULATIONINTERNEURONSFUNCTIONAL MAGNETIC RESONANCE IMAGINGSIGNAL TO NOISE RATIOSIGNAL FILTERINGPYRAMIDAL CELLSArticulohttps://doi.org/10.1371/journal.pcbi.1008737