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

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 [(11)C]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 [(11)C]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.

Fig. 1

SPM activation maps with VA during RW(first row) and during SD conditions (second row); SPM activation maps showing areas where SD>RW(third row); and SPM activation map showing areas that changed with increased VA attentional load (fourth row). Significance for all comparisons corresponds to p<0.005 not corrected. VA = visual attention, RW=rested wakefulness, SD = sleep deprivation.

Fig. 2

SPM correlation maps between VA performance (accuracy) and BOLD signals for the RW (first row) and the SD (second row) conditions. Significance for all comparisons corresponds to p<0.005 not corrected.

Fig. 3

SPM correlation maps between the changes in D2R availability in putamen and the changes in activation/deactivation BOLD (SD vs. RW) and histograms showing the activation/deactivation responses to the 3 difficulty levels (2 balls, 3 ball, 4 balls) during RW and SD and the corresponding regression plots between putamen ΔD2R and ΔBOLD (averaged across the 3 difficulty levels). Significance for SPM maps correspond to p<0.005 not corrected. Abbreviations correspond to CG cingulate gyrus, LO = lower occipital, MO = middle occipital, CB = cerebellum, 2b = 2 balls, 3b = 3 balls, and 4b = 4 balls.