Hyperstimulation of striatal D2 receptors with sleep deprivation: Implications for cognitive impairment

Nora D. Volkow, Dardo Tomasi, Gene Jack Wang, Frank Telang, Joanna S. Fowler, Ruiliang L. Wang, Jean Logan, Christopher Wong, Millard Jayne, James M. Swanson

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Sleep deprivation interferes with cognitive performance but the mechanisms are poorly understood. We recently reported that one night of sleep deprivation increased dopamine in striatum (measured with [11C]raclopride, a PET radiotracer that competes with endogenous dopamine for binding to D2 receptors) and that these increases were associated with impaired performance in a visual attention task. To better understand this association here we evaluate the relationship between changes in striatal dopamine (measured as changes in D2 receptor availability using PET and [11C]raclopride) and changes in brain activation to a visual attention task (measured with BOLD and fMRI) when performed during sleep deprivation versus during rested wakefulness. We find that sleep induced changes in striatal dopamine were associated with changes in cortical brain regions modulated by dopamine (attenuated deactivation of anterior cingulate gyrus and insula) but also in regions that are not recognized targets of dopaminergic modulation (attenuated activation of inferior occipital cortex and cerebellum). Moreover, the increases in striatal dopamine as well as its associated regional activation and deactivation patterns correlated negatively with performance accuracy. These findings therefore suggest that hyperstimulation of D2 receptors in striatum may contribute to the impairment in visual attention during sleep deprivation. Thus, while dopamine increases in prefrontal regions (including stimulation of D1 receptors) may facilitate attention our findings suggest that hyperstimulation of D2 receptors in striatum may impair it. Alternatively, these associations may reflect a compensatory striatal dopamine response (to maintain arousal) that is superimposed on a larger response to sleep deprivation.

Original languageEnglish
Pages (from-to)1232-1240
Number of pages9
JournalNeuroImage
Volume45
Issue number4
DOIs
StatePublished - 1 May 2009
Externally publishedYes

Keywords

  • Default network
  • Dopamine D2 receptors
  • PET
  • Raclopride
  • Thalamus
  • Visual attention
  • fMRI

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