Prefrontal-striatl pathway underlies cognitive regulation of craving

Division of Substance Abuse, Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06519, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 08/2010; 107(33):14811-6. DOI: 10.1073/pnas.1007779107
Source: PubMed


The ability to control craving for substances that offer immediate rewards but whose long-term consumption may pose serious risks lies at the root of substance use disorders and is critical for mental and physical health. Despite its importance, the neural systems supporting this ability remain unclear. Here, we investigated this issue using functional imaging to examine neural activity in cigarette smokers, the most prevalent substance-dependent population in the United States, as they used cognitive strategies to regulate craving for cigarettes and food. We found that the cognitive down-regulation of craving was associated with (i) activity in regions previously associated with regulating emotion in particular and cognitive control in general, including dorsomedial, dorsolateral, and ventrolateral prefrontal cortices, and (ii) decreased activity in regions previously associated with craving, including the ventral striatum, subgenual cingulate, amygdala, and ventral tegmental area. Decreases in craving correlated with decreases in ventral striatum activity and increases in dorsolateral prefrontal cortex activity, with ventral striatal activity fully mediating the relationship between lateral prefrontal cortex and reported craving. These results provide insight into the mechanisms that enable cognitive strategies to effectively regulate craving, suggesting that it involves neural dynamics parallel to those involved in regulating other emotions. In so doing, this study provides a methodological tool and conceptual foundation for studying this ability across substance using populations and developing more effective treatments for substance use disorders.

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Available from: Ethan Kross, Sep 30, 2015
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    • "What's more, its involvement in inhibitory control is regarded as a key role in drug seeking behaviors (Feil et al. 2010). Projections from several PFC regions such as the ACC, OFC and DLPFC to the striatum, passing through the pallidum and thalamus, constitute the prefrontalstriatal circuits, which are related to cognitive inhibitory control and stimulus–response habits (Volkow et al. 2013; Kober et al. 2010). Dysfunction of these circuits may be a possible underlying mechanism of addicted behaviors such as impaired inhibition-control and compulsive use despite the negative outcomes, which have been reported in subjects with IGD (Dong et al. 2010; Young 1998b). "
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    ABSTRACT: Internet Gaming Disorder (IGD) among adolescents has become an important public concern and gained more and more attention internationally. Recent studies focused on IGD and revealed brain abnormalities in the IGD group, especially the prefrontal cortex (PFC). However, the role of PFC-striatal circuits in pathology of IGD remains unknown. Twenty-five adolescents with IGD and 21 age- and gender-matched healthy controls were recruited in our study. Voxel-based morphometric (VBM) and functional connectivity analysis were employed to investigate the abnormal structural and resting-state properties of several frontal regions in individuals with online gaming addiction. Relative to healthy comparison subjects, IGD subjects showed significant decreased gray matter volume in PFC regions including the bilateral dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC) and the right supplementary motor area (SMA) after controlling for age and gender effects. We chose these regions as the seeding areas for the resting-state analysis and found that IGD subjects showed decreased functional connectivity between several cortical regions and our seeds, including the insula, and temporal and occipital cortices. Moreover, significant decreased functional connectivity between some important subcortical regions, i.e., dorsal striatum, pallidum, and thalamus, and our seeds were found in the IGD group and some of those changes were associated with the severity of IGD. Our results revealed the involvement of several PFC regions and related PFC-striatal circuits in the process of IGD and suggested IGD may share similar neural mechanisms with substance dependence at the circuit level.
    Brain Imaging and Behavior 08/2015; DOI:10.1007/s11682-015-9439-8 · 4.60 Impact Factor
    • "The importance of the insula in craving and drug seeking is reviewed by Naqvi (Naqvi et al. 2014) showing its three different and even opposite functions of incentive motivational processes that can drive addictive behavior, control processes that can inhibit and moderate addictive behavior and interoceptive processes that represent bodily states associated with drug use. The current investigation that indicates the raINS as being the key brain area for craving regulation and inhibition in long-term ex-smokers extends previous studies on short-term nicotine abstinence (Wilson et al. 2005; Wang et al. 2007; Kober et al. 2010). Taken together, our findings add a long-term perspective and temporal continuum; i.e. first, during short-term nicotine abstinence, the raINS is suggested to be responsible for craving regulation, as showed by previous studies and second, during long-term smoking cessation, our results indicate that it promotes abstinence through the enhancement and the inhibition of areas related to craving, in particular, modulating ACC activity. "
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    Addiction Biology 08/2015; DOI:10.1111/adb.12292 · 5.36 Impact Factor
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    • "For instance, inactivation of the PrL can facilitate or inhibit reinstatement of alcohol seeking in rats, depending on the context in which this behavior was extinguished (Willcocks & McNally, 2013). One view is that the PrL acts as a locus of " cognitive-control, " capable of inhibiting responses to reward-paired cues (Jonkman et al., 2009; Kober et al., 2010; Mihindou et al., 2013). In this regard, it is "
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