Cognitive control of drug craving inhibits brain reward regions in cocaine abusers

Abstract

Loss of control over drug taking is considered a hallmark of addiction and is critical in relapse. Dysfunction of frontal brain regions involved with inhibitory control may underlie this behavior. We evaluated whether addicted subjects when instructed to purposefully control their craving responses to drug-conditioned stimuli can inhibit limbic brain regions implicated in drug craving. We used PET and 2-deoxy-2[ 18 F]fluoro-D-glucose to measure brain glucose metabolism (marker of brain function) in 24 cocaine abusers who watched a cocaine-cue video and compared brain activation with and without instructions to cognitively inhibit craving. A third scan was obtained at baseline (without video). Statistical parametric mapping was used for analysis and corroborated with regions of interest. The cocaine-cue video increased craving during the no-inhibition condition (pre 3±3 post 6±3; p<0.001) but not when subjects were instructed to inhibit craving (pre 3±2 post 3±3). Comparisons with baseline showed visual activation for both cocaine-cue conditions and limbic inhibition (accumbens, orbitofrontal, insula, cingulate) when subjects purposefully inhibited craving (p<0.001). Comparison between cocaine-cue conditions showed lower metabolism with cognitive inhibition in right orbitofrontal cortex and right accumbens (p<0.005), which was associated with right inferior frontal activation (r = −0.62, P <0.005). Decreases in metabolism in brain regions that process the predictive (nucleus accumbens) and motivational value (orbitofrontal cortex) of drugconditioned stimuli was elicited by instruction to inhibit cue-induced craving. This suggests that cocaine abusers may retain some ability to inhibit craving and that strengthening frontoaccumbal regulation may be therapeutically beneficial in addiction.*Correspondence: Nora D. Volkow, M.D., National Institute on Drug Abuse, 6001 Executive Boulevard, Room 5274, Bethesda, MD 20892, Tel. (301) Fax (301) 443-9127, nvolkow@nida.nih.gov. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroimage. Author manuscript; available in PMC 2011 February 1. In addicted individuals exposure to conditioned drug-cues (i.e., places, people and paraphernalia associated with the drug) usually elicits an intense desire for the drug. This subjective experience (described as craving) frequently triggers relapse (O'Brien et al., 1998). Dopamine (DA) is a neurotransmitter involved with reward and with prediction of reward (Wise and Rompre, 1989;Schultz et al., 1997), and DA increases in the nucleus accumbens (NAcc) are asso...

Dorsolateral caudate nucleus differentiates cocaine from natural reward-associated contextual cues

“…Our data suggest that NAc plays an important role in differentiating not only the conditional stimuli but also reward types, perhaps as a function of altered activity from dopaminergic and glutamatergic neurons projecting from VTA and amygdala/prefrontal cortex, respectively (48). This speculation is consistent with the differential response to cues in amygdala and prefrontal cortex in the cocaine and sucrose groups.…”

Individual Differences in Attentional Bias Associated with Cocaine Dependence Are Related to Varying Engagement of Neural Processing Networks

“…This reliance of regulation of drug motivation on attentional awareness is central to recent attempts to use attentional bias modification training (Schoenmakers et al, 2010) and attention control training (Fadardi and Cox, 2009) to reduce drugrelated attentional bias and drug use. Prior studies have demonstrated that drug-dependent individuals can regulate their craving and neural responses by the effortful cognitive regulation of drug cues (Volkow et al, 2010;Kober et al, 2010). This study adds to this literature by demonstrating that engagement of a sensory-motor-dorsal insula network is associated with decreases in the attentional bias effect for implicitly processed cocaine cues.…”

Cocaine Cue-Induced Dopamine Release in Amygdala and Hippocampus: A High-Resolution PET [18F]Fallypride Study in Cocaine Dependent Participants

“…First, the videos contained narrative detail designed for the local milieu, and the autobiographical script would be expected to enhance these effects, but some participants might be non-responsive to the mostly impersonal cues (O'Brien et al, 1979;Staiger and White, 1991;Conklin et al, 2010). Alternatively, our low-craving participants may have had less intent to use drugs that day; active inhibition of craving can affect cue-induced appetitive states and corticolimbic activity (Wertz and Sayette, 2001;McBride et al, 2006;Volkow et al, 2010;Prisciandaro et al, 2012). Finally, recent animal studies suggest that DA responses to rewardrelated cues occur only in those subjects that imbue the cues with incentive salience; individual differences in these tendencies appear to be an inherited trait (Robinson and Flagel, 2009;Flagel et al, 2010).…”