Article

The neurobiology of cognitive control in successful cocaine abstinence

Department of Psychiatry, University of California, San Diego, USA.
Drug and alcohol dependence (Impact Factor: 3.28). 08/2011; 121(1-2):45-53. DOI: 10.1016/j.drugalcdep.2011.08.007
Source: PubMed

ABSTRACT Extensive evidence demonstrates that current cocaine abusers show hypoactivity in anterior cingulate and dorsolateral prefrontal cortex and respond poorly relative to drug-naïve controls on tests of executive function. Relatively little is known about the cognitive sequelae of long-term abstinence in cocaine addicts.
Here, we use a GO-NOGO task in which successful performance necessitated withholding a prepotent response to assay cognitive control in short- and long-term abstinent cocaine users (1-5 weeks and 40-102 weeks, respectively).
We report significantly greater activity in prefrontal, cingulate, cerebellar and inferior frontal gyrii in abstinent cocaine users for both successful response inhibitions and errors of commission. Moreover, this relative hyperactivity was present in both abstinent groups, which, in the presence of comparable behavioral performance, suggests a functional compensation.
Differences between the short- and long-abstinence groups in the patterns of functional recruitment suggest different cognitive control demands at different stages in abstinence. Short-term abstinence showed increased inhibition-related dorsolateral and inferior frontal activity indicative of the need for increased inhibitory control while long-term abstinence showed increased error-related ACC activity indicative of heightened behavioral monitoring. The results suggest that the integrity of prefrontal systems that underlie cognitive control functions may be an important characteristic of successful long-term abstinence.

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    • "The processes involved in inhibition are hypothesized to share similar mechanisms to the ability to inhibit the drug-seeking response and later relapse behaviors [19]. Indeed, inhibition has also been recognized as a primary predictor of longterm abstinence [20]. Performing inhibition requires structure and functional integrity and involves several brain regions, including the inferior frontal lobe, parietal lobe, and basal ganglia [21]. "
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    • "One reasonable proposition is that individuals who still suffer from strong impulsive tendencies are simply making greater efforts to engage inhibitory mechanisms since they are actively pursuing recovery, a matter of increased motivation. It is of note that we have previously observed hyperactivation in the RIC in a cohort of both short-and long-term abstinent cocaine users (Connolly et al., 2012), although in that study we did not relate RIC activations to impulsivity measures. Clearly, the direction of this association reduces the power of utilizing RIC activations alone to distinguish relapse risk since RIC activation is in fact " normalizing " with cocaine cessation and treatment services in most individuals. "
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    • "To determine the specificity of such an association in healthy individuals, we investigated the GM volume–N200 relationship in a neuropsychological disorder known to be associated with structural and functional impairments in the cingulate cortex: cocaine use disorder (CUD). Indeed, previous reports in CUD have shown reduced prefrontal GM volume ( Franklin et al., 2002 ; Matochik et al., 2003 ), impaired executive function including conflict monitoring as assessed with fMRI ( Connolly et al., 2012 ; Hester and Garavan, 2004 ) and anomalies in the No-go N200 amplitude ( Sokhadze et al., 2008 ). Thus, we hypothesized deficits in prefrontal GM volume and blunted N200 amplitude to negatively impact the fidelity of the GM volume–N200 association. "
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