Boosting Norepinephrine Transmission Triggers Flexible Reconfiguration of Brain Networks at Rest

Cereb Cortex. 2017 Oct 1;27(10):4691-4700. doi: 10.1093/cercor/bhw262.

Abstract

The locus coeruleus-norepinephrine (LC-NE) system is thought to act as a reset signal allowing brain network reorganization in response to salient information in the environment. However, no direct evidence of NE-dependent whole-brain reorganization has ever been described. We used resting-state functional magnetic resonance imaging in monkeys to investigate the impact of NE-reuptake inhibition on whole-brain connectivity patterns. We found that boosting NE transmission changes functional connectivity between and within resting-state networks. It modulated the functional connectivity pattern of a brainstem network including the LC region and interactions between associative and sensory-motor networks as well as within sensory-motor networks. Among the observed changes, those involving the fronto-parietal attention network exhibited a unique pattern of uncoupling with other sensory-motor networks and correlation switching from negative to positive with the brainstem network that included the LC nucleus. These findings provide the first empirical evidence of NE-dependent large-scale brain network reorganization and further demonstrate that the fronto-parietal attention network represents a central feature within this reorganization.

Keywords: atomoxetine; fronto-parietal network; locus coeruleus; monkey; resting-state fMRI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atomoxetine Hydrochloride / pharmacology
  • Attention / drug effects*
  • Attention / physiology
  • Brain / drug effects
  • Brain / physiology
  • Brain Mapping* / methods
  • Female
  • Haplorhini
  • Image Processing, Computer-Assisted / methods
  • Magnetic Resonance Imaging / methods
  • Nerve Net / drug effects
  • Nerve Net / physiology
  • Neural Pathways / drug effects
  • Neural Pathways / physiology
  • Norepinephrine / metabolism*
  • Rest / physiology*

Substances

  • Atomoxetine Hydrochloride
  • Norepinephrine