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Take it or leave it: prefrontal control in recreational cocaine users.

ABSTRACT: Though stimulant drugs such as cocaine are considered highly addictive, some individuals report recreational use over long periods without developing dependence. Difficulties in response inhibition have been hypothesized to contribute to dependence, but previous studies investigating response inhibition in recreational cocaine users have reported conflicting results. Performance on a stop-signal task was examined in 24 recreational cocaine users and 32 healthy non-drug using control participants matched for age, gender and verbal intelligence during functional magnetic resonance imaging scanning. The two groups were further matched on traumatic childhood histories and the absence of family histories of addiction. Results revealed that recreational cocaine users did not significantly differ from controls on any index of task performance, including response execution and stop-signal reaction time, with the latter averaging 198 ms in both groups. Functional magnetic resonance imaging analyses indicated that, compared with controls, stopping in the recreational users was associated with increased activation in the pre-supplementary motor area but not the right inferior frontal cortex. Thus, findings imply intact response inhibition abilities in recreational cocaine users, though the distinct pattern of accompanying activation suggests increased recruitment of brain areas implicated in response inhibition. This increased recruitment could be attributed to compensatory mechanisms that enable preserved cognitive control in this group, possibly relating to their hypothetical resilience to stimulant drug dependence. Such overactivation, alternatively, may be attributable to prolonged cocaine use leading to neuroplastic adaptations.

SUBMITTER: Morein-Zamir S

PROVIDER: S-EPMC4490290 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Take it or leave it: prefrontal control in recreational cocaine users.

Morein-Zamir S S Simon Jones P P Bullmore E T ET Robbins T W TW Ersche K D KD

Translational psychiatry 20150616

Though stimulant drugs such as cocaine are considered highly addictive, some individuals report recreational use over long periods without developing dependence. Difficulties in response inhibition have been hypothesized to contribute to dependence, but previous studies investigating response inhibition in recreational cocaine users have reported conflicting results. Performance on a stop-signal task was examined in 24 recreational cocaine users and 32 healthy non-drug using control participants ...[more]

PMID: 26080317

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Project description:Chronic cocaine use has been associated with impairments in social cognition, self-serving and antisocial behavior, and socially relevant personality disorders (PD). Despite the apparent relationship between Machiavellianism and stimulant use, no study has explicitly examined this personality concept in cocaine users so far. In the frame of the longitudinal Zurich Cocaine Cognition Study, the Machiavellianism Questionnaire (MACH-IV) was assessed in 68 recreational and 30 dependent cocaine users as well as in 68 psychostimulant-naïve controls at baseline. Additionally, three closely related personality dimensions from the Temperament and Character Inventory (TCI)-cooperativeness, (social) reward dependence, and self-directedness-and the screening questionnaire of the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II) were acquired. At the one-year follow-up, 57 cocaine users and 48 controls were reassessed with the MACH-IV. Finally, MACH-IV scores were correlated with measures of social cognition and interaction (cognitive/emotional empathy, Theory-of-Mind, prosocial behavior) and with SCID-II PD scores assessed at baseline. Both recreational and dependent cocaine users showed significantly higher Machiavellianism than controls, while dependent cocaine users additionally displayed significantly lower levels of TCI cooperativeness and self-directedness. During the one-year interval, MACH-IV scores showed high test-retest reliability and also the significant gap between cocaine users and controls remained. Moreover, in cocaine users, higher Machiavellianism correlated significantly with lower levels of cooperativeness and self-directedness, with less prosocial behavior, and with higher cluster B PD scores. However, Machiavellianism was not correlated with measures of cocaine use severity (r<-.15). Both recreational and dependent cocaine users display pronounced and stable Machiavellian personality traits. The lack of correlations with severity of cocaine use and its temporal stability indicates that a Machiavellian personality trait might represent a predisposition for cocaine use that potentially serves as a predictor for stimulant addiction.

Project description:Cue-induced craving is a significant barrier to obtaining abstinence from cocaine. Neuroimaging research has shown that cocaine cue exposure evokes elevated activity in a network of frontal-striatal brain regions involved in drug craving and drug seeking. Prior research from our laboratory has demonstrated that when targeted at the medial prefrontal cortex (mPFC), continuous theta burst stimulation (cTBS), an inhibitory form of non-invasive brain stimulation, can decrease drug cue-related activity in the striatum in cocaine users and alcohol users. However, it is known that there are individual differences in response to repetitive transcranial magnetic stimulation (rTMS), with some individuals being responders and others non-responders. There is some evidence that state-dependent effects influence response to rTMS, with baseline neural state predicting rTMS treatment outcomes. In this single-blind, active sham-controlled crossover study, we assess the striatum as a biomarker of treatment response by determining if baseline drug cue reactivity in the striatum influences striatal response to mPFC cTBS. The brain response to cocaine cues was measured in 19 cocaine-dependent individuals immediately before and after real and sham cTBS (110% resting motor threshold, 3600 total pulses). Group independent component analysis (ICA) revealed a prominent striatum network comprised of bilateral caudate, putamen, and nucleus accumbens, which was modulated by the cocaine cue reactivity task. Baseline drug cue reactivity in this striatal network was inversely related to change in striatum reactivity after real (vs. sham) cTBS treatment (ρ = -.79; p < .001; R 2 Adj = .58). Specifically, individuals with a high striatal response to cocaine cues at baseline had significantly attenuated striatal activity after real but not sham cTBS (t 9 = -3.76; p ≤ .005). These data demonstrate that the effects of mPFC cTBS on the neural circuitry of craving are not uniform and may depend on an individual's baseline frontal-striatal reactivity to cues. This underscores the importance of assessing individual variability as we develop brain stimulation treatments for addiction.

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Take it or leave it: prefrontal control in recreational cocaine users.

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Take it or leave it: prefrontal control in recreational cocaine users.

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