Widespread disruption in brain activation patterns to a working memory task during cocaine abstinence. Brain Res

Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA.
Brain Research (Impact Factor: 2.84). 10/2007; 1171(1):83-92. DOI: 10.1016/j.brainres.2007.06.102
Source: PubMed


Cocaine abstinence is associated with impaired performance in cognitive functions including attention, vigilance and executive function. Here we test the hypothesis that cognitive dysfunction during cocaine abstinence reflects in part impairment of cortical and subcortical regions modulated by dopamine. We used functional magnetic resonance imaging (fMRI) to study brain activation to a verbal working memory task in cocaine abusers (n=16) and healthy controls (n=16). Compared to controls, cocaine abusers showed: (1) hypoactivation in the mesencephalon, where dopamine neurons are located, as well as the thalamus, a brain region involved in arousal; (2) larger deactivation in dopamine projection regions (putamen, anterior cingulate, parahippocampal gyrus, and amygdala); and (3) hyperactivation in cortical regions involved with attention (prefrontal and parietal cortices), which probably reflects increased attention and control processes as compensatory mechanisms. Furthermore, the working memory load activation was lower in the prefrontal and parietal cortices in cocaine abusers when compared with controls, which might reflect limited network capacity. These abnormalities were accentuated in the cocaine abusers with positive urines for cocaine at time of study (as compared to cocaine abusers with negative urines) suggesting that the deficits may reflect in part early cocaine abstinence. These findings provide evidence of impaired function of regions involved with executive control, attention and vigilance in cocaine abusers. This widespread neurofunctional disruption is likely to underlie the cognitive deficits during early cocaine abstinence and to reflect involvement of dopamine as well as other neurotransmitters.

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Available from: Dardo Tomasi, Sep 09, 2015
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    • "One possible mechanism underlying this difference is an impairment of working memory in cocaine addiction. Indeed, many previous studies have shown impaired working memory as a result of chronic exposure to cocaine (Albein-Urios et al., 2012; Fisk et al., 2011; Jovanovski et al., 2005; Kalapatapu et al., 2011; Kalechstein et al., 2013; Kubler et al., 2005; Lundqvist, 2005; Moeller et al., 2010; Porter et al., 2011; Rosselli and Ardila, 1996; Tau et al., 2013; Tomasi et al., 2007; Vonmoos et al., 2013). Since chronic cocaine use compromises cerebral structures critical for working memory and the extent of the structural deficits is related to years of drug use (Ide et al., 2014), more research is needed to confirm a lack of association between altered sequential effect and drug use. "
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    ABSTRACT: Cocaine dependence is associated with cognitive control deficits. Here, we apply a Bayesian model of stop-signal task (SST) performance to further characterize these deficits in a theory-driven framework. A "sequential effect" is commonly observed in SST: encounters with a stop trial tend to prolong reaction time (RT) on subsequent go trials. The Bayesian model accounts for this by assuming that each stop/go trial increases/decreases the subject's belief about the likelihood of encountering a subsequent stop trial, P(stop), and that P(stop) strategically modulates RT accordingly. Parameters of the model were individually fit, and compared between cocaine-dependent (CD, n=51) and healthy control (HC, n=57) groups, matched in age and gender and both demonstrating a significant sequential effect (p<0.05). Model-free measures of sequential effect, post-error slowing (PES) and post-stop slowing (PSS), were also compared across groups. By comparing individually fit Bayesian model parameters, CD were found to utilize a smaller time window of past experiences to anticipate P(stop) (p<0.003), as well as showing less behavioral adjustment in response to P(stop) (p<0.015). PES (p=0.19) and PSS (p=0.14) did not show group differences and were less correlated with the Bayesian account of sequential effect in CD than in HC. Cocaine dependence is associated with the utilization of less contextual information to anticipate future events and decreased behavioral adaptation in response to changes in such anticipation. These findings constitute a novel contribution by providing a computationally more refined and statistically more sensitive account of altered cognitive control in cocaine addiction. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Drug and alcohol dependence 04/2015; 151. DOI:10.1016/j.drugalcdep.2015.03.021 · 3.42 Impact Factor
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    • "From a neurophysiological perspective, craving is initiated when the reward pathways, habituated with frequent and intense firing of dopamine neurons from the mesocorticolimbic projections to the nucleus accumbens and DLPFC, are kept relatively understimulated for a certain period of time, as when one remains abstinent. Several functional magnetic resonance imaging (fMRI) studies have demonstrated that abstinence-induced craving increases cerebral blood flow and neuronal activity in the DLPFC, nucleus accumbens, and limbic structures including the hippocampus and amygdala (Tomasi et al., 2007; Wang et al., 2007). Thus, it is generally accepted that addiction is initiated by chronic and repetitive overstimulation of the dopamine pathways, but its maintenance is highly dependent on more complex cerebral mechanisms, such as emotional regulation and memory. "
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    ABSTRACT: Craving is recognized as an important diagnosis criterion for substance use disorders (SUDs) and a predictive factor of relapse. Various methods to study craving exist; however, suppressing craving to successfully promote abstinence remains an unmet clinical need in SUDs. One reason is that social and environmental contexts recalling drug and alcohol consumption in the everyday life of patients suffering from SUDs often initiate craving and provoke relapse. Current behavioral therapies for SUDs use the cue-exposure approach to suppress salience of social and environmental contexts that may induce craving.They facil- itate learning and cognitive reinforcement of new behavior and entrain craving suppression in the presence of cues related to drug and alcohol consumption. Unfortunately, craving often overweighs behavioral training especially in real social and environmental contexts with peer pressure encouraging the use of substance, such as parties and bars. In this perspective, virtual reality (VR) is gaining interest in the development of cue-reactivity par- adigms and practices new skills in treatment. VR enhances ecological validity of traditional craving-induction measurement. In this review, we discuss results from (1) studies using VR and alternative virtual agents in the induction of craving and (2) studies combining cue- exposure therapy with VR in the promotion of abstinence from drugs and alcohol use. They used virtual environments, displaying alcohol and drugs to SUD patients. Moreover, some environments included avatars. Hence, some studies have focused on the social interac- tions that are associated with drug-seeking behaviors and peer pressure. Findings indicate that VR can successfully increase craving. Studies combining cue–exposure therapy with virtual environment, however, reported mitigated success so far.
    Frontiers in Human Neuroscience 10/2014; 8(1):1-15. DOI:10.3389/fnhum.2014.00844/abstract · 3.63 Impact Factor
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    • "Cocaine Dependence (CD) is associated with neurobiological changes in the prefrontal cortex (PFC; Tomasi et al., 2007), impulsivity , and executive function (EF) deficits (Cunha et al., 2013; Noël et al., 2013; Cunha et al., 2011; Verdejo-Garcia et al., 2007). Executive functioning is defined as the complex ability of a person to respond in an adaptive manner to new situations, depending on a variety of executive domains such as motivation, working memory, and inhibitory control (Lezak et al., 2004). "
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    ABSTRACT: BACKGROUND: In cocaine-dependent individuals, executive function (EF) deficits are associated with poor treatment outcomes. Psychological interventions and pharmacological approaches have produced only modest effect sizes. To date, studies of this topic have been few and limited. The aim of this study was to examine the effects of a new model of intervention, which integrates chess and Motivational Interviewing, Motivational Chess (MC) METHODS: We evaluated 46 cocaine-dependent inpatients (aged 18-45), in two groups-MC (n=26); and active comparison-AC (n=20). Using neuropsychological tests and an impulsivity scale, we assessed the subjects before and after the study period (one month of abstinence monitored by urine toxicology screening). RESULTS: The MC and AC groups did not differ at baseline. In the post-intervention assessment (after one month), both groups showed significant improvements in attention, mental flexibility, inhibitory control, abstraction abilities, and decision-making (p<0.01). In addition, the improvement in working memory was more significant in the MC group than in the AC group (group-by-time interaction, p=01). CONCLUSIONS: One month of abstinence was sufficient to improve various attentional and executive domains in cocaine-dependent subjects. The MC intervention was associated with greater improvements in EFs, especially working memory, suggesting that tailored interventions focusing on complex EFs accelerate the process of cognitive recovery during the initial period of abstinence.
    Drug and Alcohol Dependence 07/2014; 140:e70. DOI:10.1016/j.drugalcdep.2014.02.210 · 3.42 Impact Factor
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