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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1700-1702
Number of pages3
JournalScience
Volume322
Issue number5908
DOIs
StatePublished - Dec 12 2008

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