Ersche KD, Barnes A, Jones PS, Morein-Zamir S, Robbins TW, Bullmore ET. Abnormal structure of frontostriatal brain systems is associated with aspects of impulsivity and compulsivity in cocaine dependence. Brain 134(Pt 7): 2013-2024

University of Cambridge, Department of Psychiatry, Herchel Smith Building for Brain and Mind Sciences, Cambridge Biomedical Campus, Cambridge CB20SZ, UK.
Brain (Impact Factor: 9.2). 07/2011; 134(Pt 7):2013-24. DOI: 10.1093/brain/awr138
Source: PubMed


A growing body of preclinical evidence indicates that addiction to cocaine is associated with neuroadaptive changes in frontostriatal brain systems. Human studies in cocaine-dependent individuals have shown alterations in brain structure, but it is less clear how these changes may be related to the clinical phenotype of cocaine dependence characterized by impulsive behaviours and compulsive drug-taking. Here we compared self-report, behavioural and structural magnetic resonance imaging data on a relatively large sample of cocaine-dependent individuals (n = 60) with data on healthy volunteers (n = 60); and we investigated the relationships between grey matter volume variation, duration of cocaine use, and measures of impulsivity and compulsivity in the cocaine-dependent group. Cocaine dependence was associated with an extensive system of abnormally decreased grey matter volume in orbitofrontal, cingulate, insular, temporoparietal and cerebellar cortex, and with a more localized increase in grey matter volume in the basal ganglia. Greater duration of cocaine dependence was correlated with greater grey matter volume reduction in orbitofrontal, cingulate and insular cortex. Greater impairment of attentional control was associated with reduced volume in insular cortex and increased volume of caudate nucleus. Greater compulsivity of drug use was associated with reduced volume in orbitofrontal cortex. Cocaine-dependent individuals had abnormal structure of corticostriatal systems, and variability in the extent of anatomical changes in orbitofrontal, insular and striatal structures was related to individual differences in duration of dependence, inattention and compulsivity of cocaine consumption.

Download full-text


Available from: Anna Barnes,
    • "An underlying assumption is that these behavioral attributes reflect the abnormal function of key brain areas that are also part of the addiction circuitry and that respond to drug abuse in a maladaptive way, triggering addiction. In this regard, magnetic resonance studies have associated cocaine addiction with macrostructural abnormalities (i.e., volume alterations) in the limbic brain regions that are involved in motivational, cognitive and emotional behavior, such as the frontal cortices and temporal lobe structures, including the amygdala but usually not the hippocampus [12] [13] [14] [15] [16] [17] [18] [19]. Nevertheless, it is difficult for human studies to elucidate whether the maladaptive behavioral traits and the neurobiological hallmarks found in addicts actually predispose individuals to cocaine addiction or if they are a consequence of the neuroadaptations induced by prolonged drug intake. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The identification of behavioral traits that could predict an individual's susceptibility to engage in cocaine addiction is relevant for understanding and preventing this disorder, but investigations of cocaine addicts rarely allow us to determinate whether their behavioral attributes are a cause or a consequence of drug use. To study the behaviors that predict cocaine vulnerability, male C57BL/6J mice were examined in a battery of tests (the elevated plus maze, hole-board, novelty preference in the Y-Maze, episodic-like object recognition and forced swimming) prior to training in a cocaine-conditioned place preference (CPP) paradigm to assess the reinforcing value of the drug. In a second study, the anatomical basis of high and low CPP in the mouse brain was investigated by studying the number of neurons (neuronal nuclei-positive) in two addiction-related limbic regions (the medial prefrontal cortex and the basolateral amygdala) and the number of dopaminergic neurons (tyrosine hydroxylase-positive) in the ventral tegmental area by immunohistochemistry and stereology. Correlational analyses revealed that CPP behavior was successfully predicted by anxiety-like measures in the elevated plus maze (i.e., the more anxious mice showed more preference for the cocaine-paired compartment) but not by the other behaviors analyzed. In addition, increased numbers of neurons were found in the basolateral amygdala of the high CPP mice, a key brain center for anxiety and fear responses. The results support the theory that anxiety is a relevant factor for cocaine vulnerability, and the basolateral amygdala is a potential neurobiological substrate where both anxiety and cocaine vulnerability could overlap.
    Behavioural brain research 11/2015; 298(Pt B). DOI:10.1016/j.bbr.2015.10.048 · 3.03 Impact Factor
  • Source
    • "First, our results are cross-sectional, and precise causal inferences between trait impulsivity and risk behavior cannot be made. For instance, substance use may result in an increase in impulsiveness or sensation seeking over time (Ersche et al., 2011; Littlefield, Vergés, Wood, & Sher, 2012), and correlational data in either cross-sectional or longitudinal designs is not sufficient for ensuring causal precedence of impulsive traits. Second , as mentioned previously, these results represent findings among a community sample of college-enrolled young adults; two critical future directions include extending these findings to younger adolescent populations—among whom the developmental asymmetry is theoretically paramount in predicting externalizing and other risk behavior—as well as vulnerable populations such as clinical samples and incarcerated youth. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Young adulthood is a peak period for externalizing behaviors such as substance abuse and antisocial conduct. Evidence from developmental neuroscience suggests that externalizing conduct within this time period may be associated with a "developmental asymmetry" characterized by an early peak in sensation seeking combined with a relatively immature impulse control system. Trait measures of impulsivity - sensation seeking and premeditation - are psychological manifestations of these respective systems, and multiple prior studies suggest that high sensation seeking and low premeditation independently confer risk for distinct forms of externalizing behaviors. The goal of the present study was to test this developmental asymmetry hypothesis, examining whether trait premeditation moderates the effect of sensation seeking on substance use and problems, aggression, and rule-breaking behavior. Using a cross-sectional sample of college-enrolled adults (n = 491), we applied zero-inflated modeling strategies to examine the likelihood and level of risky externalizing behaviors. Results indicated that lower premeditation enhanced the effect of higher sensation seeking on higher levels of positive and negative alcohol consequences, more frequent drug use, and more problematic drug use, but was unrelated to individual differences in antisocial behaviors. Our findings indicate that the developmental asymmetry between sensation seeking and a lack of premeditation is a risk factor for individual differences in problematic substance use among young adults, and may be less applicable for antisocial behaviors among high functioning individuals.
    Psychology of Addictive Behaviors 09/2015; 29(3):753-765. DOI:10.1037/adb0000075 · 2.09 Impact Factor
    • "However, regions of gray matter loss in probands, including the OFC and anterior insula, did not show any change in the relatives. These changes may well occur as a consequence of stimulant drug taking, especially as some of the changes (e.g., in the OFC) were related to duration of drug use as well as to measures of compulsive behavior (Ersche et al. 2011a). This is consistent with longitudinal findings in rhesus monkeys exposed to cocaine self-administration (Porrino et al. 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: A decade ago, we hypothesized that drug addiction can be viewed as a transition from voluntary, recreational drug use to compulsive drug-seeking habits, neurally underpinned by a transition from prefrontal cortical to striatal control over drug seeking and taking as well as a progression from the ventral to the dorsal striatum. Here, in the light of burgeoning, supportive evidence, we reconsider and elaborate this hypothesis, in particular the refinements in our understanding of ventral and dorsal striatal mechanisms underlying goal-directed and habitual drug seeking, the influence of drug-associated Pavlovian-conditioned stimuli on drug seeking and relapse, and evidence for impairments in top-down prefrontal cortical inhibitory control over this behavior. We further review animal and human studies that have begun to define etiological factors and individual differences in the propensity to become addicted to drugs, leading to the description of addiction endophenotypes, especially for cocaine addiction. We consider the prospect of novel treatments for addiction that promote abstinence from and relapse to drug use. Expected final online publication date for the Annual Review of Psychology Volume 67 is January 03, 2016. Please see for revised estimates.
    Annual Review of Psychology 08/2015; 67(1). DOI:10.1146/annurev-psych-122414-033457 · 21.81 Impact Factor
Show more