Elsevier

NeuroImage

Volume 49, Issue 3, 1 February 2010, Pages 2536-2543
NeuroImage

Cognitive control of drug craving inhibits brain reward regions in cocaine abusers

https://doi.org/10.1016/j.neuroimage.2009.10.088Get rights and content

Abstract

Loss of control over drug taking is considered a hallmark of addiction and is critical in relapse. Dysfunction of frontal brain regions involved with inhibitory control may underlie this behavior. We evaluated whether addicted subjects when instructed to purposefully control their craving responses to drug-conditioned stimuli can inhibit limbic brain regions implicated in drug craving. We used PET and 2-deoxy-2[18F]fluoro-d-glucose to measure brain glucose metabolism (marker of brain function) in 24 cocaine abusers who watched a cocaine-cue video and compared brain activation with and without instructions to cognitively inhibit craving. A third scan was obtained at baseline (without video). Statistical parametric mapping was used for analysis and corroborated with regions of interest. The cocaine-cue video increased craving during the no-inhibition condition (pre 3 ± 3, post 6 ± 3; p < 0.001) but not when subjects were instructed to inhibit craving (pre 3 ± 2, post 3 ± 3). Comparisons with baseline showed visual activation for both cocaine-cue conditions and limbic inhibition (accumbens, orbitofrontal, insula, cingulate) when subjects purposefully inhibited craving (p < 0.001). Comparison between cocaine-cue conditions showed lower metabolism with cognitive inhibition in right orbitofrontal cortex and right accumbens (p < 0.005), which was associated with right inferior frontal activation (r =  0.62, p < 0.005). Decreases in metabolism in brain regions that process the predictive (nucleus accumbens) and motivational value (orbitofrontal cortex) of drug-conditioned stimuli were elicited by instruction to inhibit cue-induced craving. This suggests that cocaine abusers may retain some ability to inhibit craving and that strengthening fronto-accumbal regulation may be therapeutically beneficial in addiction.

Section snippets

Subjects

Twenty four active cocaine abusers (21 M and 3 F; 46 ± 5 years of age) who responded to an advertisement were studied. Subjects fulfilled DSM- IV criteria for cocaine dependence and were active users for at least the prior 6 months (free-base or crack) with average cocaine use of 16 ± 2 days per month; 2.2 ± 1 g/day; and 17 ± 6 years of abuse. Exclusion criteria included current or past psychiatric disease other than cocaine or nicotine dependence (12 subjects were smokers); past or present history of

Effects of cocaine video NI and CI on craving and on cardiovascular measures

The behavioral assessment comparing the pre versus the post video measures of craving revealed that the cocaine-cue video elicited significant increases in subjective reports of craving in the NI condition but not in the CI condition. There was no pre–post difference in self-reports of craving for the corresponding times of assessment during the baseline condition (Fig. 1). Heart rate and blood pressure were significantly increased after watching the cocaine-cue video (NI and CI) whereas they

Discussion

Our findings provide evidence that when cocaine abusers purposefully inhibit craving when exposed to conditioned drug-cues, specific changes in brain regions that process reward and prediction of reward occur. Namely when subjects were instructed to inhibit cue-induced craving (CI), metabolic activity decreased in the right NAcc and in the right medial OFC (mOFC) when compared with the condition with no inhibition instructions (NI) or when compared with the baseline condition. The decrease with

Acknowledgments

We thank David Schlyer, David Alexoff, Don Warner, Paul Vaska, Colleen Shea, Youwen Xu, Lisa Muench, Barbara Hubbard, Pauline Carter, Karen Apelskog, Alex Reben and Linda Thomas for their contributions. Research supported by NIH’s Intramural Research Program (NIAAA), by DOE (DE-AC01-76CH00016).

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