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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Available from: John J Foxe, Jul 14, 2015
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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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    ABSTRACT: This study aimed to determine the effect of acute exercise in the potential context of non-pharmacological intervention for methamphetamine (MA)-related craving; we additionally determine its effect on the inhibitory control induced by standard and MA-related tasks according to behavioral and neuroelectric measurements among MA-dependent individuals. The present study employed a within-subjects, counterbalanced design. A total of 24 participants who met the DSM-IV criteria for MA dependence were recruited. The craving level, reaction time, and response accuracy, as well as the event-related potential (ERP) components N2 and P3, were measured following exercise and the control treatment in a counterbalanced order. The exercise session consisted of an acute stationary cycle exercise at a moderate intensity, whereas the control treatment consisted of an active reading session. The self-reported MA craving was significantly attenuated during, immediately following, and 50min after the exercise session compared with the pre-exercise ratings, whereas the craving scores at these time points following exercise were lower than those for the reading control session. Acute exercise also facilitated inhibitory performance in both the standard and MA-related Go/Nogo tasks. A larger N2 amplitude, but not a larger P3 amplitude, was observed during both tasks in the exercise session and the Nogo condition compared with the reading control session and the Go condition. This is the first empirical study to demonstrate these beneficial effects of acute aerobic exercise at a moderate intensity on MA-related craving and inhibitory control in MA-dependent individuals. These results suggest a potential role for acute aerobic exercise in treating this specific type of substance abuse. Copyright © 2015. Published by Elsevier Inc.
    Physiology & Behavior 04/2015; 147. DOI:10.1016/j.physbeh.2015.04.008 · 3.03 Impact Factor
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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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    ABSTRACT: A significant hindrance to effective treatment of addiction is the difficulty encountered in identifying those most likely to relapse. Cocaine addiction is characterized by deficits in inhibitory control and elevated reactivity to cocaine cues, both hypothesized to be integral to the development of addiction and propensity to relapse. It follows that reduction of both impulsivity and cue-reactivity following abstinence is protective against relapse, and that persistence of these factors increases vulnerability. Using functional magnetic resonance imaging, we examined neural activation patterns in dorsal and ventral striatum in abstinent cocaine dependent (CD) individuals (N=20) and non-using controls (N=19) as they performed a cocaine craving task. We also examined activations in nodes of the response inhibition circuit (RIC) as they performed an inhibition task. At the between-groups level, no differences in RIC or striatal activation were seen in former users, in contrast to previous investigations in current users, suggesting large-scale functional recovery with abstinence. However, at the individual participant-level, abstinent CD individuals displayed an association between cocaine cue-related neural activations in the right ventral striatum and compulsive cocaine craving scores. Compulsive craving scores were also negatively correlated with duration of abstinence. Further, there was an association between motor impulsivity scores and inhibition-related activations in the right inferior frontal gyrus and pre-supplementary motor area in abstinent CD individuals. Thus, while former users as a group did not show deficits in inhibitory function or cocaine-cue reactivity, participant-level results pointed to activation patterns in a minority of these individuals that likely contributes to enduring relapse vulnerability.
    Neuropharmacology 06/2014; 85. DOI:10.1016/j.neuropharm.2014.05.011 · 4.82 Impact Factor
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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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    ABSTRACT: Functional neuroimaging studies have long implicated the mid-cingulate cortex (MCC) in conflict monitoring, but it is not clear whether its structural integrity (i.e., the gray matter volume) influences its conflict monitoring function. In this multimodal study, we used T1-weighted MRI scans as well as event-related potentials (ERPs) to test whether the MCC gray matter volume is associated with the electrocortical marker (i.e., No-go N200 ERP component) of conflict monitoring in healthy individuals. The specificity of such a relationship in health was determined in two ways: by (A) acquiring the same data from individuals with cocaine use disorder (CUD), known to have deficits in executive function including behavioral monitoring; and (B) acquiring the P300 ERP component that is linked with attention allocation and not specifically with conflict monitoring. Twenty-five (39.1 ± 8.4 years; 8 females) healthy individuals and 25 (42.7 ± 5.9 years; 6 females) individuals with CUD underwent a rewarded Go/No-go task during which the ERP data was collected, and they also underwent a structural MRI scan. The whole brain regression analysis showed a significant correlation between MCC structural integrity and the well-known ERP measure of conflict monitoring (N200, but not the P300) in healthy individuals, which was absent in CUD who were characterized by reduced MCC gray matter volume, N200 abnormalities as well as reduced task accuracy. In individuals with CUD instead, the N200 amplitude was associated with drug addiction symptomatology. These results show that the integrity of MCC volume is directly associated with the electrocortical correlates of conflict monitoring in healthy individuals, and such an association breaks down in psychopathologies that impact these brain processes. Taken together, this MCC-N200 association may serve as a biomarker of improved behavioral monitoring processes in diseased populations.
    06/2014; 5:10-8. DOI:10.1016/j.nicl.2014.05.011
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