Executive Dysfunction in Cocaine Addiction: Evidence for Discordant Frontal, Cingulate, and Cerebellar Activity

Medical College of Wisconsin, Milwaukee, Wisconsin, United States
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 01/2005; 24(49):11017-22. DOI: 10.1523/JNEUROSCI.3321-04.2004
Source: PubMed


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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    • "ously highlighted in addicts by using the stop-signal task (i.e., prolonged latency of motor response inhibition), and the Go/No-Go paradigm (i.e., more errors of commission: subject had to withhold a response but pressed a button instead) (for a review of response inhibition impairment in gambling , opiate and alcohol addiction, see respectively Brevers & Noël, 2013; Goldstein & Volkow, 2011; Noël et al., 2010). Moreover, results from several brain imaging studies showed that, in drug addicts (Hester & Garavan, 2004), impaired performance on response inhibition tasks is associated with a hypoactivation in the anterior cingulate cortex, implicated in mechanisms of error detection and conflict monitoring. "
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    ABSTRACT: Paradoxical behaviours characterizing an addiction could be understood as the result of a combination between an attempt to cope with dominant painful feelings (e.g., anxiety with low self-esteem) and sub-optimal decision-making prioritizing short-term over long-term consequences. This article focused on decision-making and emphasized that addicts' decisions are determined by immediate outcomes because of abnormal interactions between key neural and cognitive systems: (1) an automatic, habitual and salient information processing mediated by amygdala-striatum dependent system; (2) an intention self-regulatory system forecasting the future consequences of a choice; (3) a interoceptive signals processing system which generates feeling states and in turn plays a strong influential role in decision-making and impulse control processes related to uncertainty, risk, and reward. As a whole, sub-optimal interactions such as a too strong automatic stimulus-driven actions associated with poor intentional control and a state of stress or craving are thought to result in prioritizing short-term consequences at the detriment of the necessary forecast of delayed consequences.
    Neuropsychological Trends 04/2015; 17(17):2015. DOI:10.7358/neur-2015-017-noel · 0.15 Impact Factor
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    • "We employed an emotional Go / NoGo task ( see Donders , 1868 / 1969 ; Hester and Garavan , 2004 ) , which presented emo - tional distractor pictures simultaneously with the Go and NoGo stimuli . In each trial , the participant was shown a square or cir - cle , lasting 2 s , which served as the Go or NoGo stimulus ( see Figure 1 ) . "
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    ABSTRACT: Improved neuroscientific understanding of high-risk behaviors such as alcohol binging, drug use, and unsafe sex will lead to therapeutic advances for high-risk groups. High-risk behavior often occurs in an emotionally-charged context, and behavioral inhibition and emotion regulation play important roles in risk-related decision making. High impulsivity is an important potential contributor to high-risk behavior tendencies. We explored the relationships between high-risk behavior tendencies, impulsivity, and fMRI brain activations in an emotional Go/NoGo task. This task presented emotional distractor pictures (aversive vs. neutral) simultaneously with Go/NoGo stimuli (square vs. circle) that required a button press or withholding of the press, respectively. Participants' risk behavior tendencies were assessed with the Cognitive Appraisal of Risky Events (CARE) scale. The Barratt Impulsivity Scale 11 (BIS) was used to assess participant impulsivity. Individuals with higher CARE risk scores exhibited reduced activation related to response inhibition (NoGo−Go) in right orbital frontal cortex (OFC) and ventromedial prefrontal cortex. These regions did not show a significant relationship with impulsivity scores. Conversely, more impulsive individuals showed reduced emotion-related activity (aversive−neutral distractors) in dorsomedial prefrontal cortex, perigenual anterior cingulate cortex, and right posterior OFC. There were distinct neural correlates of high-risk behavior tendency and impulsivity in terms of brain activity in the emotional Go/NoGo task. This dissociation supports the conception of high-risk behavior tendency as a distinct construct from that of impulsivity. Our results suggest that treatment for high-risk behavior may be more effective with a nuanced approach that does not conflate high impulsivity necessarily with high-risk behavior tendencies.
    Frontiers in Systems Neuroscience 03/2015; 9. DOI:10.3389/fnsys.2015.00024
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    • "There is a growing literature associating SUD with deficits in executive function and cognitive control using tasks, like the CWIT, that require inhibition of prepotent response tendencies [Giancola and Moss, 1998; Li and Sinha, 2008; Lyvers, 2000; Mintzer and Stitzer, 2002]. The dACC and dlPFC clusters identified in the present functional connectivity analysis are particularly notable for their overlap with regions shown to be hypoactive during a response inhibition task in cocaine users [Hester and Garavan, 2004; Kaufman et al., 2003]. The concordance of our rsFC and behavioral task results with previous fMRItask data supports the assertion that the regions identified in the present between-groups analysis (fO, dACC, dlPFC, and IPL) are involved in cognitive-behavioral control, and moreover, that functional coherence between the NAc and these regions may be a neurobiological correlate of cognitive control efficacy that is compromised in SUD. "
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    ABSTRACT: Substance use disorders (SUD) have been associated with dysfunction in reward processing, habit formation, and cognitive-behavioral control. Accordingly, neurocircuitry models of addiction highlight roles for nucleus accumbens, dorsal striatum, and prefrontal/anterior cingulate cortex. However, the precise nature of the disrupted interactions between these brain regions in SUD, and the psychological correlates thereof, remain unclear. Here we used magnetic resonance imaging to measure rest-state functional connectivity of three key striatal nuclei (nucleus accumbens, dorsal caudate, and dorsal putamen) in a sample of 40 adult male prison inmates (n = 22 diagnosed with SUD; n = 18 without SUD). Relative to the non-SUD group, the SUD group exhibited significantly lower functional connectivity between the nucleus accumbens and a network of frontal cortical regions involved in cognitive control (dorsal anterior cingulate cortex, dorsolateral prefrontal cortex, and frontal operculum). There were no group differences in functional connectivity for the dorsal caudate or dorsal putamen. Moreover, the SUD group exhibited impairments in laboratory measures of cognitive-behavioral control, and individual differences in functional connectivity between nucleus accumbens and the frontal cortical regions were related to individual differences in measures of cognitive-behavioral control across groups. The strength of the relationship between functional connectivity and cognitive control did not differ between groups. These results indicate that SUD is associated with abnormal interactions between subcortical areas that process reward (nucleus accumbens) and cortical areas that govern cognitive-behavioral control. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
    Human Brain Mapping 09/2014; 35(9). DOI:10.1002/hbm.22474 · 5.97 Impact Factor
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