Boosting Norepinephrine Transmission Triggers Flexible Reconfiguration of Brain Networks at Rest.
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.
ImpAct Team, Lyon Neuroscience Research Center, INSERM U1028, CNRS UMR5292, Lyon F-69000, France.|University UCBL Lyon 1, F-69000, France.
Carole
C
Guedj
ImpAct Team, Lyon Neuroscience Research Center, INSERM U1028, CNRS UMR5292, Lyon F-69000, France.|University UCBL Lyon 1, F-69000, France.|Institut de Médecine Environnementale, Paris F-75007, France.
Elisabetta
E
Monfardini
ImpAct Team, Lyon Neuroscience Research Center, INSERM U1028, CNRS UMR5292, Lyon F-69000, France.|University UCBL Lyon 1, F-69000, France.
Amélie J
AJ
Reynaud
ImpAct Team, Lyon Neuroscience Research Center, INSERM U1028, CNRS UMR5292, Lyon F-69000, France.|University UCBL Lyon 1, F-69000, France.
Alessandro
A
Farnè
ImpAct Team, Lyon Neuroscience Research Center, INSERM U1028, CNRS UMR5292, Lyon F-69000, France.|University UCBL Lyon 1, F-69000, France.
Martine
M
Meunier
ImpAct Team, Lyon Neuroscience Research Center, INSERM U1028, CNRS UMR5292, Lyon F-69000, France.|University UCBL Lyon 1, F-69000, France.
Fadila
F
Hadj-Bouziane
D000818:Animals; D000069445:Atomoxetine Hydrochloride / Q000494:pharmacology; D001288:Attention / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000502:physiology; D001931:Brain Mapping / Q000379:methods; D005260:Female; D000882:Haplorhini; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism*; D012146:Rest / Q000502:physiology*
D000069445:Atomoxetine Hydrochloride; D009638:Norepinephrine
atomoxetine; fronto-parietal network; locus coeruleus; monkey; resting-state fMRI