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Modafinil Shifts Human Locus Coeruleus to Low-Tonic, High-Phasic Activity During Functional MRI
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Modafinil Shifts Human Locus Coeruleus to Low-Tonic, High-Phasic Activity During Functional MRI
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Journal Article
Modafinil Shifts Human Locus Coeruleus to Low-Tonic, High-Phasic Activity During Functional MRI
2008
Overview
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.
Publisher
American Association for the Advancement of Science,The American Association for the Advancement of Science
Subject
/ Benzhydryl Compounds - administration & dosage
/ Benzhydryl Compounds - pharmacology
/ Biological and medical sciences
/ Central Nervous System Stimulants - pharmacology
/ Female
/ Fundamental and applied biological sciences. Psychology
/ Humans
/ loci
/ Locus Coeruleus - drug effects
/ Locus Coeruleus - physiology
/ Male
/ NMR
/ Norepinephrine Plasma Membrane Transport Proteins - antagonists & inhibitors
/ Norepinephrine Plasma Membrane Transport Proteins - metabolism
/ Placebos
/ Prefrontal Cortex - physiology
/ Primates
