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Subjective sensitivity to monetary gradients is associated with frontolimbic activation to reward in cocaine abusers.

ABSTRACT: Drug addiction is characterized by marked disruptions in the ability to process reward. Here we evaluated in cocaine addicted and healthy control participants the subjective sensitivity to reward gradients and its association with neural responses to sustained reward. A self-report questionnaire was used to assess the former. A functional magnetic resonance imaging task that utilized monetary reward as feedback in a blocked design was used to assess the latter. Results revealed that whereas control subjects valued high money more than low money, over half of the cocaine addicted subjects valued all monetary amounts equally. This compromised subjective sensitivity to gradients in reward value was significantly correlated with higher activations to money in the lateral orbitofrontal cortex/inferior frontal gyrus (BA 47) and amygdala, and lower activations in the middle frontal gyrus (BA 6), which together explained 85% of the variability on this rating scale in the cocaine abusers only. These results provide for the first time evidence of restricted subjective sensitivity to gradients of reward in cocaine addiction and of the involvement of frontolimbic brain regions (including the orbitofrontal cortex) in this deficit.

SUBMITTER: Goldstein RZ

PROVIDER: S-EPMC2435043 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature

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Subjective sensitivity to monetary gradients is associated with frontolimbic activation to reward in cocaine abusers.

Goldstein Rita Z RZ Tomasi Dardo D Alia-Klein Nelly N Cottone Lisa A LA Zhang Lei L Telang Frank F Volkow Nora D ND

Drug and alcohol dependence 20060925 2-3

Drug addiction is characterized by marked disruptions in the ability to process reward. Here we evaluated in cocaine addicted and healthy control participants the subjective sensitivity to reward gradients and its association with neural responses to sustained reward. A self-report questionnaire was used to assess the former. A functional magnetic resonance imaging task that utilized monetary reward as feedback in a blocked design was used to assess the latter. Results revealed that whereas cont ...[more]

PMID: 16997508

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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

Subjective sensitivity to monetary gradients is associated with frontolimbic activation to reward in cocaine abusers.

Publications

Subjective sensitivity to monetary gradients is associated with frontolimbic activation to reward in cocaine abusers.

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