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Science 12 December 2008:
Vol. 322. no. 5908, pp. 1700 - 1702
DOI: 10.1126/science.1164908
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Reports

Modafinil Shifts Human Locus Coeruleus to Low-Tonic, High-Phasic Activity During Functional MRI

Michael J. Minzenberg,* Andrew J. Watrous, Jong H. Yoon, Stefan Ursu, Cameron S. Carter

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.

Department of Psychiatry, University of California, Davis School of Medicine, Sacramento, CA, USA.

* To whom correspondence should be addressed. E-mail: michael.minzenberg{at}ucdmc.ucdavis.edu

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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