Modafinil shifts human locus coeruleus to low-tonic, high-phasic activity during functional MRI.

Author(s): Minzenberg MJ, Watrous AJ, Yoon JH, Ursu S, Carter CS

Affiliation(s): Department of Psychiatry, University of California, Davis School of Medicine, Sacramento, CA, USA. michael.minzenberg@ucdmc.ucdavis.edu

Publication date & source: 2008-12-12, Science., 322(5908):1700-2.

Publication type: Randomized Controlled Trial; Research Support, N.I.H., Extramural

Models of cognitive control posit a key modulatory role for the pontine locus coeruleus-norepinephrine (LC-NE) system. In nonhuman primates, phasic LC-NE activity confers adaptive adjustments in cortical gain in task-relevant brain networks, and in performance, on a trial-by-trial basis. This model has remained untested in humans. We used the pharmacological agent modafinil to promote low-tonic/high-phasic LC-NE activity in healthy humans performing a cognitive control task during event-related functional magnetic resonance imaging (fMRI). Modafanil administration was associated with decreased task-independent, tonic LC activity, increased task-related LC and prefrontal cortex (PFC) activity, and enhanced LC-PFC functional connectivity. These results confirm in humans the role of the LC-NE system in PFC function and cognitive control and suggest a mechanism for therapeutic action of procognitive noradrenergic agents.