Goldstein RZ, Volkow ND. Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications. Nat Rev Neurosci 12: 652-669

Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USA.
Nature Reviews Neuroscience (Impact Factor: 31.43). 11/2011; 12(11):652-69. DOI: 10.1038/nrn3119
Source: PubMed


The loss of control over drug intake that occurs in addiction was initially believed to result from disruption of subcortical reward circuits. However, imaging studies in addictive behaviours have identified a key involvement of the prefrontal cortex (PFC) both through its regulation of limbic reward regions and its involvement in higher-order executive function (for example, self-control, salience attribution and awareness). This Review focuses on functional neuroimaging studies conducted in the past decade that have expanded our understanding of the involvement of the PFC in drug addiction. Disruption of the PFC in addiction underlies not only compulsive drug taking but also accounts for the disadvantageous behaviours that are associated with addiction and the erosion of free will.

    • "Yet, the understanding of addiction has changed markedly in the last sixty years. The modern conceptualization of addiction is biobehavioral and emphasizes that the combination of individual risk factors (e.g., genetics, age of first use) and exposure to an addictive substance or behavior (e.g., cocaine, gambling) can trigger neuroplastic changes in brain systems implicated in compulsive behavior (e.g., mesolimbic dopaminergic system)192021. Though it has been suggested that this model may not change stigma[22], or even increase it[23], by labeling individuals as " diseased " or lacking control and overemphasizing the medicalization of treat- ment[24], it is also plausible that a biobehavioral perspective will decrease stigma by reducing blame on the individual and increasing funding for intervention research[25]. "
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    ABSTRACT: Objectives: This study examines whether belief in the food addiction construct is associated with support for obesity-related policies (e.g., restrictions on foods served in schools and workplace cafeterias, subsidies on fruits and vegetables), while simultaneously examining other factors associated with policy support (e.g., political party affiliation). Design: Cross-sectional. Setting: Online Community. Participants: 200 individuals were recruited through Amazon Mechanical Turk. Measurements: Participants (n = 193) responded to three questions about belief in food addiction and a measure evaluating support for 13 obesity-related policy initiatives. Individuals also completed the modified Yale Food Addiction Scale (mYFAS), self-reported height and weight, and provided demographic information (age, gender, race, political party affiliation). Results: Belief in food addiction was significantly associated with greater support for obesity-related initiatives, even when accounting for the significant associations of age, gender, and political party. Belief in food addiction and political party both had moderate effect sizes for predicting support for obesity-related policy. There was an interaction between age and belief in food addiction, with significant associations with policy support for both younger and older individuals, though the effect was larger for younger participants. Conclusion: The current study provides evidence that belief in food addiction is associated with increased obesity-related policy support, comparable to the influence of one's political party. Growing evidence for the role of an addictive process in obesity may have important implications for public support of obesity-related policy initiatives.
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    • "Reductions in dopamine receptor density in the ACC and its decreased engagement have been associated with poor behavioral monitoring and loss of control over drug intake (Volkow et al. 2012). Analogous receptor modifications in the OFC are believed to alter salience attribution (Goldstein & Volkow 2011;Volkow et al. 2012). Also, a recent study in animals has shown that whereas ventral striatal activity signals reward prior to decision making, the OFC shows post-decision activation. "
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    ABSTRACT: Cocaine addiction has been associated with increased sensitivity of the human reward circuit to drug-related stimuli. However, the capacity of non-drug incentives to engage this network is poorly understood. Here, we characterized the functional sensitivity to monetary incentives and the structural integrity of the human reward circuit in abstinent cocaine-dependent (CD) patients and their matched controls. We assessed the BOLD response to monetary gains and losses in 30 CD patients and 30 healthy controls performing a lottery task in a magnetic resonance imaging scanner. We measured brain gray matter volume (GMV) using voxel-based morphometry and white matter microstructure using voxel-based fractional anisotropy (FA). Functional data showed that, after monetary incentives, CD patients exhibited higher activation in the ventral striatum than controls. Furthermore, we observed an inverted BOLD response pattern in the prefrontal cortex, with activity being highest after unexpected high gains and lowest after losses. Patients showed increased GMV in the caudate and the orbitofrontal cortex, increased white matter FA in the orbito-striatal pathway but decreased FA in antero-posterior association bundles. Abnormal activation in the prefrontal cortex correlated with GMV and FA increases in the orbitofrontal cortex. While functional abnormalities in the ventral striatum were inversely correlated with abstinence duration, structural alterations were not. In conclusion, results suggest abnormal incentive processing in CD patients with high salience for rewards and punishments in subcortical structures but diminished prefrontal control after adverse outcomes. They further suggest that hypertrophy and hyper-connectivity within the reward circuit, to the expense of connectivity outside this network, characterize cocaine addiction.
    Full-text · Article · Jan 2016 · Addiction Biology
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    • "The PFC plays a major role in several addiction‐related neural functions, including decision making (Fu et al., 2008; Gilbert et al., 2006), impulsivity (Rao et al., 2008), self‐control (Brody et al., 2007), emotional regulation (Kringelbach & Rolls, 2004; Wang et al., 2010), motivation and salience attribution (Ventura et al., 2007). Whereas there is increasing evidence that the PFC makes an important contribution to the cycle of addiction (Goldstein & Volkow, 2011), the role of PFC function post‐withdrawal as it relates to relapse, or risk of relapse, remains unclear. "
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    ABSTRACT: Anhedonia is an important but understudied element of a neuroadaptive model underlying vulnerability to relapse in opioid dependence. Previous research using fMRI has shown reduced activation to pleasant stimuli in rostral prefrontal cortex among heroin-dependent patients in early recovery. This study evaluated the presence of anhedonia among recently withdrawn prescription opiate dependent patients (PODP) in residential treatment compared to control subjects. Anhedonia was assessed using self-report, affect-modulated startle response (AMSR), and a cue reactivity task during which participant's rostral prefrontal cortex (RPFC) and ventrolateral prefrontal cortex (VLPFC) was monitored with functional near infrared spectroscopy (fNIRS). The cue reactivity task included three distinct categories of natural reward stimuli: highly palatable food, positive social situations, and intimate (non-erotic) interactions. PODP reported greater anhedonia on self-report (Snaith-Hamilton Pleasure Scale), and showed reduced hedonic response to positive stimuli in the AMSR task relative to controls. PODP also exhibited reduced neural activation in bilateral RPFC and left VLPFC in response to food images and reduced left VLPFC in response to images depicting positive social situations relative to controls. No differences were found for emotionally intimate stimuli. When patients were divided into groups based on the Snaith-Hamilton criteria for the presence or absence of anhedonia, patients endorsing anhedonia showed reduced neural responses to images depicting positive social stimuli and food relative to patients who did not endorse anhedonia. Activations were in areas of RPFC that support the retrieval of episodic memories. The results suggest the presence of anhedonia in a subsample of PODP.
    Full-text · Article · Dec 2015 · Brain research bulletin
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