Addiction, compulsive drug seeking, and the role of frontostriatal mechanisms in regulating inhibitory control

School of Psychology and Psychiatry, Monash University, Clayton, Victoria 3800, Australia.
Neuroscience & Biobehavioral Reviews (Impact Factor: 8.8). 03/2010; 35(2):248-75. DOI: 10.1016/j.neubiorev.2010.03.001
Source: PubMed


A principal feature of drug addiction is a reduced ability to regulate control over the desire to procure drugs regardless of the risks involved. Traditional models implicated the neural 'reward' system in providing a neurobiological model of addiction. Newer models however, have expanded on this circuitry to include two separate, but interconnecting systems, the limbic system in the incentive sensitization of drugs, and the prefrontal cortex (PFC) in regulating inhibitory control over drug use. Until the recent developments in neuroimaging and brain stimulation techniques, it has been extremely difficult to assess the involvement of the PFC in addiction. In the current review, we explore the involvement of the frontostriatal circuitry in regulating inhibitory control, and suggest how dysregulation of these circuits could be involved in an increased difficulty in ceasing drug use. Following this, we investigate the recent neuropsychological, neuroimaging and brain stimulation studies that explore the presence of these inhibitory deficits, and frontostriatal dysfunctions, across various different substance groups. Further insight into these deficits could contribute to the development of treatment strategies which target these cognitive impairments, and frontostriatal dysfunction, in reducing drug-seeking behaviors.

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    • "The PFC is connected to several subcortical regions and plays an important role in regulation of reward systems (Volkow et al. 2009). 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). "
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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
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    • "Recent models of drug addiction have begun to emphasize the reciprocal influence of incentive-motivational properties of drug-related cues and impaired control over drug taking (Dawe et al., 2004; Feil et al., 2010). These models cite neuroanatomical evidence implicating frontostriatal circuitry dysfunction in salience attribution and response inhibition, and propose that the motivation elicited by drug-associated cues serve to directly impair control mechanisms necessary to inhibit the cue-induced impulse to use a drug. "
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    DESCRIPTION: Background: Models of drug addiction emphasize the reciprocal influence of incentive-motivational properties of drug-related cues and poor impulse control resulting in drug use. Recent studies have shown that alcohol-related cues can impair response inhibition. What is unknown is whether these cues also disrupt learning of inhibitory associations. Methods: Participants performed a conditioned inhibition (CI) task and were required to learn that a neutral image was a conditioned inhibitor when presented in the context of either an alcohol image intended to draw their attention away from the to-be-trained inhibitor, or a control condition in which the alcohol image was absent. After training, subjects in each condition rated the likelihood that the neutral image would signal the outcome. Eye tracking was used to verify that attention to the neutral image was in fact reduced when the alcohol image was present. Results: Compared with controls those trained in the alcohol image condition reported a greater likelihood that the presence of the inhibitor would be followed by the outcome and thus were less able to acquire CI. Measures of eye tracking verified that attention to the alcohol cue was associated with this maladaptive behavior. Conclusions: When alcohol cues are present, there is a reduced ability to learn that such information is irrelevant to an outcome, and this impairs ones’ ability to inhibit perseveration of a response. This has implications for persistence of a drinking episode.
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    • "Recent models of drug addiction emphasize the reciprocal influence of incentive-motivational properties of drug-related cues and impaired inhibitory control over drug taking (Dawe & Loxton, 2004; Feil et al., 2010; Goldstein & Volkow, 2002; Jentsch & Taylor, 1999). These models cite neuroanatomical evidence implicating frontostriatal circuitry dysfunction in both salience attribution and response inhibition, and propose that the intense motivation elicited by drug-associated cues could serve to directly impair control mechanisms necessary to inhibit the cue-induced impulse. "
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