Structural and behavioral correlates of abnormal encoding of money value in the sensorimotor striatum in cocaine addiction

Medical Research, Brookhaven National Laboratory, Upton, NY, USA Department of Psychology, Stony Brook University, Stony Brook, NY, USA National Institute on Alcohol and Alcoholism, Bethesda, MD, USA National Institute on Drug Abuse, Bethesda, MD, USA.
European Journal of Neuroscience (Impact Factor: 3.18). 07/2012; 36(7):2979-88. DOI: 10.1111/j.1460-9568.2012.08211.x
Source: PubMed


Abnormalities in frontostriatal systems are thought to be central to the pathophysiology of addiction, and may underlie the maladaptive processing of the highly generalizable reinforcer, money. Although abnormal frontostriatal structure and function have been observed in individuals addicted to cocaine, it is less clear how individual variability in brain structure is associated with brain function to influence behavior. Our objective was to examine frontostriatal structure and neural processing of money value in chronic cocaine users and closely matched healthy controls. A reward task that manipulated different levels of money was used to isolate neural activity associated with money value. Gray matter volume measures were used to assess frontostriatal structure. Our results indicated that cocaine users had an abnormal money value signal in the sensorimotor striatum (right putamen/globus pallidus) that was negatively associated with accuracy adjustments to money and was more pronounced in individuals with more severe use. In parallel, group differences were also observed in both the function and gray matter volume of the ventromedial prefrontal cortex; in the cocaine users, the former was directly associated with response to money in the striatum. These results provide strong evidence for abnormalities in the neural mechanisms of valuation in addiction and link these functional abnormalities with deficits in brain structure. In addition, as value signals represent acquired associations, their abnormal processing in the sensorimotor striatum, a region centrally implicated in habit formation, could signal disadvantageous associative learning in cocaine addiction.

Download full-text


Available from: Anna Konova,
1 Follower
23 Reads
  • Source
    • "A recent review suggests that the presence of drug cues may modulate reward circuitry activation, where drug cues enhance reward circuitry activation relative to controls, but natural rewards produce lower levels of activity (Leyton and Vezina, 2013; Limbrick-Oldfield et al., 2013). Corroborating this, several studies using monetary or food rewards have shown that individuals with SUDs relative to controls show decreased activation in the striatum, amygdala and insula when viewing or receiving rewards (Ihssen et al., 2011; Jia et al., 2011; Konova et al., 2012; Peters et al., 2011). The ability to stimulate reward circuitry through natural rewards may diminish the desire to stimulate it through substance use, potentially reducing the risk of relapse. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Nearly half of individuals with substance use disorders relapse in the year after treatment. A diagnostic tool to help clinicians make decisions regarding treatment does not exist for psychiatric conditions. Identifying individuals with high risk for relapse to substance use following abstinence has profound clinical consequences. This study aimed to develop neuroimaging as a robust tool to predict relapse. 68 methamphetamine-dependent adults (15 female) were recruited from 28-day inpatient treatment. During treatment, participants completed a functional MRI scan that examined brain activation during reward processing. Patients were followed 1 year later to assess abstinence. We examined brain activation during reward processing between relapsing and abstaining individuals and employed three random forest prediction models (clinical and personality measures, neuroimaging measures, a combined model) to generate predictions for each participant regarding their relapse likelihood. 18 individuals relapsed. There were significant group by reward-size interactions for neural activation in the left insula and right striatum for rewards. Abstaining individuals showed increased activation for large, risky relative to small, safe rewards, whereas relapsing individuals failed to show differential activation between reward types. All three random forest models yielded good test characteristics such that a positive test for relapse yielded a likelihood ratio 2.63, whereas a negative test had a likelihood ratio of 0.48. These findings suggest that neuroimaging can be developed in combination with other measures as an instrument to predict relapse, advancing tools providers can use to make decisions about individualized treatment of substance use disorders. Published by Elsevier Ireland Ltd.
    Drug and alcohol dependence 04/2015; 152. DOI:10.1016/j.drugalcdep.2015.04.018 · 3.42 Impact Factor
  • Source
    • "An earlier study of alcohol dependent individuals also demonstrated that comorbid cocaine use disorder did not account for any independent variance in volumetric measures (Bjork et al., 2003). Similarly, only a few studies considered the effects of aging (Alia-Klein et al., 2011; Bartzokis et al., 2000; Konova et al., 2012; Tanabe et al., 2009). An earlier work reported an increased agerelated decline in temporal but not frontal cortical GM in stimulant dependent individuals as compared to healthy controls (Bartzokis et al., 2000). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Magnetic resonance imaging has provided a wealth of information on altered brain activations and structures in individuals addicted to cocaine. However, few studies have considered the influence of age and alcohol use on these changes. We examined gray matter volume with voxel based morphometry (VBM) and low frequency fluctuation (LFF) of BOLD signals as a measure of cerebral activity of 84 cocaine dependent (CD) and 86 healthy control (HC) subjects. We performed a covariance analysis to account for the effects of age and years of alcohol use. Compared to HC, CD individuals showed decreased gray matter (GM) volumes in frontal and temporal cortices, middle/posterior cingulate cortex, and the cerebellum, at p<0.05, corrected for multiple comparisons. The GM volume of the bilateral superior frontal gyri (SFG) and cingulate cortices were negatively correlated with years of cocaine use, with women showing a steeper loss in the right SFG in association with duration of use. In contrast, the right ventral putamen showed increased GM volume in CD as compared to HC individuals. Compared to HC, CD individuals showed increased fractional amplitude of LFF (fALFF) in the thalamus, with no significant overlap with regions showing GM volume loss. These results suggested that chronic cocaine use is associated with distinct changes in cerebral structure and activity that can be captured by GM volume and fALFF of BOLD signals.
    Drug and alcohol dependence 09/2013; 134(134). DOI:10.1016/j.drugalcdep.2013.09.004 · 3.42 Impact Factor
  • Source
    • "That is, while BOLD signal increases generally to a monetary reward in cocaine users, it does not scale with the amount or magnitude. This result has been replicated several times and is associated with altered P300 and striatal signaling, chronicity of drug use, impairments in self-control, and even lack of insight (Goldstein et al. 2007a; Konova et al. 2012; Moeller et al. 2012; Parvaz et al. 2012). The latter speculation is particularly intriguing in light of the current results, since insight arguably depends upon the same process of mental simulation that characterizes model-based processing. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Addiction is characterized by maladaptive decision-making, in which individuals seem unable to use adverse outcomes to modify their behavior. Adverse outcomes are often infrequent, delayed, and even rare events, especially when compared to the reliable rewarding drug-associated outcomes. As a result, recognizing and using information about their occurrence put a premium on the operation of so-called model-based systems of behavioral control, which allow one to mentally simulate outcomes of different courses of action based on knowledge of the underlying associative structure of the environment. This suggests that addiction may reflect, in part, drug-induced dysfunction in these systems. Here, we tested this hypothesis. This study aimed to test whether cocaine causes deficits in model-based behavior and learning independent of requirements for response inhibition or perception of costs or punishment. We trained rats to self-administer sucrose or cocaine for 2 weeks. Four weeks later, the rats began training on a sensory preconditioning and inferred value blocking task. Like devaluation, normal performance on this task requires representations of the underlying task structure; however, unlike devaluation, it does not require either response inhibition or adapting behavior to reflect aversive outcomes. Rats trained to self-administer cocaine failed to show conditioned responding or blocking to the preconditioned cue. These deficits were not observed in sucrose-trained rats nor did they reflect any changes in responding to cues paired directly with reward. These results imply that cocaine disrupts the operation of neural circuits that mediate model-based behavioral control.
    Psychopharmacology 08/2013; 229(3). DOI:10.1007/s00213-013-3222-6 · 3.88 Impact Factor
Show more