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

PLoS Comput Biol. 2021 Feb 18;17(2):e1008737. doi: 10.1371/journal.pcbi.1008737. eCollection 2021 Feb.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biophysical Phenomena
  • Brain / diagnostic imaging
  • Brain / physiology*
  • Cholinergic Neurons / physiology
  • Computational Biology
  • Computer Simulation
  • Connectome*
  • Electroencephalography
  • Feedback, Physiological
  • Humans
  • Interneurons / physiology
  • Magnetic Resonance Imaging
  • Models, Neurological*
  • Nerve Net / diagnostic imaging
  • Nerve Net / physiology
  • Neural Pathways / diagnostic imaging
  • Neural Pathways / physiology
  • Neurotransmitter Agents / physiology

Substances

  • Neurotransmitter Agents

Grants and funding

This work was supported by Fondo Nacional de Desarrollo Científico y Tecnológico - Fondecyt Grants 1181076 (to PO) and 11181072 (to RC) and the Advanced Center for Electrical and Electronic Engineering - ANID (FB0008 to PO). The Centro Interdisciplinario de Neurociencia de Valparaíso (CINV) is a Millenium Institute supported by the ANID grant ICN09_022. CC-O is funded by Beca Doctorado Nacional – ANID grant 2018- 21180995. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.