The neurobiology of cognitive control in successful cocaine abstinence

Department of Psychiatry, University of California, San Diego, USA.
Drug and alcohol dependence (Impact Factor: 3.42). 08/2011; 121(1-2):45-53. DOI: 10.1016/j.drugalcdep.2011.08.007
Source: PubMed


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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    • "Error processing refers to monitoring performance, detecting errors, and modifying behaviour adaptively in the absence of overt reinforcement (Holroyd and Coles, 2002). Error processing dysfunction has been demonstrated in several psychiatric conditions, including schizophrenia (Becerril et al., 2011; Mathalon et al., 2009; Morris et al., 2008), depression (Chiu and Deldin, 2007; Steele et al., 2004; Tucker et al., 2003) and a range of drug dependencies (Connolly et al., 2012; Easdon et al., 2005; Forman et al., 2004; Li et al., 2010). In all these conditions, the dysfunction is characterised by hypoactivity in the error-related network, most consistently in the dorsal anterior cingulate gyrus (dACC). "
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    ABSTRACT: The chronic use of cannabis has been associated with error processing dysfunction, in particular, hypoactivity in the dorsal anterior cingulate cortex (dACC) during the processing of cognitive errors. Given the role of such activity in influencing post-error adaptive behaviour, we hypothesised that chronic cannabis users would have significantly poorer learning from errors. Fifteen chronic cannabis users (four females, mean age=22.40 years, SD=4.29) and 15 control participants (two females, mean age=23.27 years, SD=3.67) were administered a paired associate learning task that enabled participants to learn from their errors, during fMRI data collection. Compared with controls, chronic cannabis users showed (i) a lower recall error-correction rate and (ii) hypoactivity in the dACC and left hippocampus during the processing of error-related feedback and re-encoding of the correct response. The difference in error-related dACC activation between cannabis users and healthy controls varied as a function of error type, with the control group showing a significantly greater difference between corrected and repeated errors than the cannabis group. The present results suggest that chronic cannabis users have poorer learning from errors, with the failure to adapt performance associated with hypoactivity in error-related dACC and hippocampal regions. The findings highlight a consequence of performance monitoring dysfunction in drug abuse and the potential consequence this cognitive impairment has for the symptom of failing to learn from negative feedback seen in cannabis and other forms of dependence. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Full-text · Article · Jul 2015 · Drug and alcohol dependence
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    • "That is, certain individuals or groups may differ in the frequency with which they commit errors, and/or in the reactivity they show upon committing such errors. One important individual difference is the presence of a substance use disorder (SUD), a psychopathology marked by pervasive and disruptive neurocognitive disruptions (e.g., in error-related processing) that modulate the severity and course of the disease [10] [11] [12] [13] [14] [15] [16] [17] [18] [19]. Our goal in the current study was to explore whether error-related processing in SUD is further modulated by another potentially important individual difference: opioid system genetics [specifically , a single nucleotide polymorphism (SNP) of the protein-coding proenkephalin gene (PENK: rs2609997)]. "
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    ABSTRACT: Chronic exposure to drugs of abuse perturbs the endogenous opioid system, which plays a critical role in the development and maintenance of addictive disorders. Opioid genetics may therefore play an important modulatory role in the expression of substance use disorders, but these genes have not been extensively characterized, especially in humans. In the current imaging genetics study, we investigated a single nucleotide polymorphism (SNP) of the protein-coding proenkephalin gene ( PENK: rs2609997, recently shown to be associated with cannabis dependence) in 55 individuals with cocaine use disorder and 37 healthy controls. Analyses tested for PENK associations with fMRI response to error (during a classical color-word Stroop task) and gray matter volume (voxel-based morphometry) as a function of Diagnosis (cocaine, control). Results revealed whole-brain Diagnosis × PENK interactions on the neural response to errors (fMRI error>correct contrast) in the right putamen, left rostral anterior cingulate cortex/medial orbitofrontal cortex, and right inferior frontal gyrus; there was also a significant Diagnosis × PENK interaction on right inferior frontal gyrus gray matter volume. These interactions were driven by differences between individuals with cocaine use disorders and controls that were accentuated in individuals carrying the higher-risk PENK C-allele. Taken together, the PENK polymorphism - and potentially opioid neurotransmission more generally - modulates functioning and structural integrity of brain regions previously implicated in error-related processing. PENK could potentially render a subgroup of individuals with cocaine use disorder (i.e., C-allele carriers) more sensitive to mistakes or other related challenges; in future studies, these results could contribute to the development of individualized genetics-informed treatments. Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · Jul 2015 · Behavioural brain research
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    • "These effects may be reversed after its discontinuation (De Oliveira et al., 2009). Prefrontal cortex (PFC) dysfunction with regard to regulation of limbic reward regions and its involvement in high-order executive function (self-control , salience attribution, and awareness) has been associated with the loss of control over drug use (Goldstein and Volkow, 2011; Connolly et al., 2012), which is an important characteristic of addiction (Garavan et al., 2008). Dorsolateral PFC (dlPFC) activity is highly required when executive control of cognition is required (Kane and Engle, 2002; Enriquez-Geppert et al., 2013). "
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    Full-text · Article · Jun 2015 · The International Journal of Neuropsychopharmacology
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