Dataset Information

Executive dysfunction and reward dysregulation: a high-density electrical mapping study in cocaine abusers.

ABSTRACT: Executive function deficits and reward dysregulation, which mainly manifests as anhedonia, are well documented in drug abusers. We investigated specific aspects of executive function (inhibitory control and cognitive control), as well as anhedonia, in a cohort of current cocaine abusers in order to ascertain to what extent these factors are associated with more severe drug dependence. Participants filled out questionnaires relating to anhedonia and their addiction history. Participants also performed a response inhibition task while high-density event-related potentials (ERPs) were recorded. Electrophysiological responses to successful inhibitions (N2/P3 components) and to commission errors (ERN/Pe components) were compared between 23 current users of cocaine and 27 non-using controls. A regression model was performed to determine the association of our measures of reward dysregulation and executive function with addiction severity. As expected, cocaine users performed more poorly than controls on the inhibitory control task and showed significant electrophysiological differences. They were also generally more anhedonic than controls. Higher levels of anhedonia were associated with more severe substance use, whereas the level of executive dysfunction was not associated with more severe substance use. However, N2 amplitude was associated with duration of drug use. Further, inhibitory control and anhedonia were correlated, but only in controls. These data suggest that while executive dysfunction characterizes drug abuse, it is anhedonia, independent of executive dysfunction, that is most strongly associated with more severe use.

SUBMITTER: Morie KP

PROVIDER: S-EPMC4385568 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Executive dysfunction and reward dysregulation: a high-density electrical mapping study in cocaine abusers.

Morie Kristen P KP De Sanctis Pierfilippo P Garavan Hugh H Foxe John J JJ

Neuropharmacology 20140606

Executive function deficits and reward dysregulation, which mainly manifests as anhedonia, are well documented in drug abusers. We investigated specific aspects of executive function (inhibitory control and cognitive control), as well as anhedonia, in a cohort of current cocaine abusers in order to ascertain to what extent these factors are associated with more severe drug dependence. Participants filled out questionnaires relating to anhedonia and their addiction history. Participants also perf ...[more]

PMID: 24911989

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Project description:Dopamine (phasic release) is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate) on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function) was measured with PET and (18)FDG in 24 active cocaine abusers tested four times; twice watching a Neutral video (nature scenes) and twice watching a Cocaine-cues video; each video was preceded once by placebo and once by methylphenidate (20 mg). The Cocaine-cues video increased craving to the same extent with placebo (68%) and with methylphenidate (64%). In contrast, SPM analysis of metabolic images revealed that differences between Neutral versus Cocaine-cues conditions were greater with placebo than methylphenidate; whereas with placebo the Cocaine-cues decreased metabolism (p<0.005) in left limbic regions (insula, orbitofrontal, accumbens) and right parahippocampus, with methylphenidate it only decreased in auditory and visual regions, which also occurred with placebo. Decreases in metabolism in these regions were not associated with craving; in contrast the voxel-wise SPM analysis identified significant correlations with craving in anterior orbitofrontal cortex (p<0.005), amygdala, striatum and middle insula (p<0.05). This suggests that methylphenidate's attenuation of brain reactivity to Cocaine-cues is distinct from that involved in craving. Cocaine-cues decreased metabolism in limbic regions (reflects activity over 30 minutes), which contrasts with activations reported by fMRI studies (reflects activity over 2-5 minutes) that may reflect long-lasting limbic inhibition following activation. Studies to evaluate the clinical significance of methylphenidate's blunting of cue-induced limbic inhibition may help identify potential benefits of this medication in cocaine addiction.

Dataset Information

Executive dysfunction and reward dysregulation: a high-density electrical mapping study in cocaine abusers.

Publications

Executive dysfunction and reward dysregulation: a high-density electrical mapping study in cocaine abusers.

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