Executive dysfunction in cocaine addiction: Evidence for discordant frontal, cingulate, and cerebellar activity
ABSTRACT Using a GO-NOGO response inhibition task in which working memory (WM) demands can be varied, we demonstrate that the compromised abilities of cocaine users to exert control over strong prepotent urges are associated with reduced activity in anterior cingulate and right prefrontal cortices, two regions thought to be critical for implementing cognitive control. Furthermore, unlike drug-naive controls, and opposite to the anterior cingulate pattern, cocaine users showed an over-reliance on the left cerebellum, a compensatory pattern previously seen in alcohol addiction. The results indicate that cocaine users find it difficult to inhibit their own actions, particularly when WM demands, which have been shown previously to increase during cue-induced craving for the drug, are increased. The results reveal a neuroanatomical basis for this dysexecutive component to addiction, supporting the suggested importance cognitive functions may play in prolonging abuse or predisposing users toward relapse.
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ABSTRACT: Altered impulse control is associated with substance use disorders, including cocaine dependence. We sought to identify the neural correlates of impulse control in abstinent male patients with cocaine dependence (PCD). Functional magnetic resonance imaging (fMRI) was conducted during a stop signal task that allowed trial-by-trial evaluation of response inhibition. Fifteen male PCD and 15 healthy control (HC) subjects, matched in age and years of education, were compared. Stop signal reaction time (SSRT) was derived on the basis of a horse race model. By comparing PCD and HC co-varied for stop success rate, task-related frustration rating, and post-error slowing, we isolated the neural substrates of response inhibition, independent of attentional monitoring (of the stop signal) and post-response processes including affective responses and error monitoring. Using region of interest analysis, we found no differences between HC and PCD who were matched in stop signal performance in the pre-supplementary motor area (pre-SMA) previously shown to be associated with SSRT. However, compared with HC, PCD demonstrated less activation of the rostral anterior cingulate cortex (rACC), an area thought to be involved in the control of stop signal inhibition. The magnitude of rACC activation also correlated negatively with the total score and the impulse control subscore of the Difficulty in Emotion Regulation Scale in PCD. The current study thus identified the neural correlates of altered impulse control in PCD independent of other cognitive processes that may influence stop signal performance. Relative hypoactivation of the rACC during response inhibition may represent a useful neural marker of difficulties in impulse control in abstinent cocaine-dependent men who are at risk of relapse.Neuropsychopharmacology 08/2008; 33(8):1798-806. DOI:10.1038/sj.npp.1301568 · 7.83 Impact Factor
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ABSTRACT: The current effectiveness of preventative and therapeutic interventions for substance use disorders (SUDs) is less than satisfying. Progress in understanding the processes related to the onset, course, and cessation of SUDs merits top priority, given the high prevalence and the severe negative consequences. This position paper, after summarizing major factors related to onset and cessation processes, discusses the possible role of cognitive-control dysfunctions in the complex interaction between mechanisms of change (mediators) and risk factors (moderators). In past decades, research has expanded our knowledge about the impact of SUDs on human behaviour. Formal interventions are effective, but there is limited information about the mechanisms responsible for change during the onset and cessation of SUDs and for individual differences related to them. Preliminary results suggest that impairments in higher order control functions play a role in SUDs. Deficiencies in our understanding of behaviour-change processes during the onset and cessation of SUDs require that research have a different focus. A better understanding of the relevance of impairments in executive-control functions might help to improve formal preventative and therapeutic interventions and social conditions. Such interventions might reduce the chances that a SUD will develop or increase the likelihood of recovery from it.International Journal of Methods in Psychiatric Research 06/2008; 17 Suppl 1(S1):S4-S15. DOI:10.1002/mpr.246 · 3.42 Impact Factor
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ABSTRACT: The consumption of cannabis has been linked to impairments in human learning and memory, as well as aspects of executive functioning. Cannabis-related impairments in learning and memory in chronic cannabis users, it has been argued, are caused by the effects of cannabis on hippocampal functioning. The current study involved two experiments. Experiment 1 compared 35 current users of cannabis and 38 well-matched controls on a face-name task, previously shown to activate the hippocampal region. Based on the results of experiment 1, experiment 2 used fMRI and a modified version of the face-name task, to examine cortical and (para)hippocampal activity during learning and recall in 14 current users of cannabis and 14 controls. Results of experiment 1 showed that cannabis users were significantly worse with respect to learning, short and long-term memory performance. Experiment 2 showed that despite non-significant differences in learning and memory performance, cannabis users had significantly lower levels of BOLD activity in the right superior temporal gyrus, right superior frontal gyrus, right middle frontal gyrus and left superior frontal gyrus compared to controls during learning. Results also showed that cannabis users had significantly higher BOLD activity in the right parahippocampal gyrus during learning. Hypoactivity in frontal and temporal cortices, and relative hyperactivity in the parahippocampus identify functional deficits and compensatory processes in cannabis users.NeuroImage 05/2008; 40(3):1328-39. DOI:10.1016/j.neuroimage.2007.12.059 · 6.13 Impact Factor