Neuroimaging reward, craving, learning, and cognitive control in substance use disorders: review and implications for treatment.

Substance use disorder is a leading causes of preventable disease and mortality. Drugs of abuse cause molecular and cellular changes in specific brain regions and these neuroplastic changes are thought to play a role in the transition to uncontrolled drug use. Neuroimaging has identified neural substrates associated with problematic substance use and may offer clues to reduce its burden on the patient and society. Here, we provide a narrative review of neuroimaging studies that have examined the structures and circuits associated with reward, cues and craving, learning, and cognitive control in substance use disorders. Most studies use advanced MRI or positron emission tomography (PET). Many studies have focused on the dopamine neurons of the ventral tegmental area, and the regions where these neurons terminate, such as the striatum and prefrontal cortex. Decreases in dopamine receptors and transmission have been found in chronic users of drugs, alcohol, and nicotine. Recent studies also show evidence of differences in structure and function in substance users relative to controls in brain regions involved in salience evaluation, such as the insula and anterior cingulate cortex. Balancing between reward-related bottom-up and cognitive-control-related top-down processes is discussed in the context of neuromodulation as a potential treatment. Finally, some of the challenges for understanding substance use disorder using neuroimaging methods are discussed.

Brain cortical thickness in male adolescents with serious substance use and conduct problems.

BACKGROUND: Adolescents with substance use disorder (SUD) and conduct problems exhibit high levels of impulsivity and poor self-control. Limited work to date tests for brain cortical thickness differences in these youths. OBJECTIVES: To investigate differences in cortical thickness between adolescents with substance use and conduct problems and controls. METHODS: We recruited 25 male adolescents with SUD, and 19 male adolescent controls, and completed structural 3T magnetic resonance brain imaging. Using the surface-based morphometry software FreeSurfer, we completed region-of-interest (ROI) analyses for group cortical thickness differences in left, and separately right, inferior frontal gyrus (IFG), orbitofrontal cortex (OFC) and insula. Using FreeSurfer, we completed whole-cerebrum analyses of group differences in cortical thickness. RESULTS: Versus controls, the SUD group showed no cortical thickness differences in ROI analyses. Controlling for age and IQ, no regions with cortical thickness differences were found using whole-cerebrum analyses (though secondary analyses co-varying IQ and whole-cerebrum cortical thickness yielded a between-group cortical thickness difference in the left posterior cingulate/precuneus). Secondary findings showed that the SUD group, relative to controls, demonstrated significantly less right > left asymmetry in IFG, had weaker insular-to-whole-cerebrum cortical thickness correlations, and showed a positive association between conduct disorder symptom count and cortical thickness in a superior temporal gyrus cluster. CONCLUSION: Functional group differences may reflect a more nuanced cortical morphometric difference than ROI cortical thickness. Further investigation of morphometric differences is needed. If replicable findings can be established, they may aid in developing improved diagnostic or more targeted treatment approaches.

Impaired Decision-Making, Higher Impulsivity, and Drug Severity in Substance Dependence and Pathological Gambling.

OBJECTIVES: Substance use disorder is characterized by impaired decision making, impulsivity, and risk taking. Pathological gambling shares many of these characteristics, and having both diagnoses may be associated with greater problems than either diagnosis alone. We investigated whether among substance-dependent individuals, comorbid pathological gambling would be associated with worse decision making, greater impulsivity, risk taking, and drug severity. METHODS: Ninety-six substance-dependent individuals were recruited from a residential treatment program and divided into 1 of the 2 groups depending on whether they met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for pathological gambling (SDPG, n = 26) or not (SD, n = 70). Ninety-two controls were recruited from the community. Participants completed a decision-making task (modified Iowa Gambling Task), measures of impulsivity (Barratt Impulsivity Scale and Delay Discounting), and risk taking (Balloon Analog Risk Task). Decision making was analyzed using a computational model. We tested for group differences using analysis of covariance or Kruskal-Wallis and appropriate post-hoc tests. RESULTS: The groups differed in decision-making parameters (P < 0.001) and self-reported impulsivity (P < 0.001). All post-hoc comparisons were significant on these measures, and indicated stepwise changes in controls, followed by SD, followed by SDPG, with SDPG performing worse on decision making and being more impulsive. Compared with SD, SDPG had greater drug severity (P < 0.001). No group differences were observed in delay discounting or risk taking. CONCLUSIONS: Compared with individuals with substance dependence without pathological gambling, those with both disorders demonstrated worse decision making and significantly more drug-related symptoms. When evaluating patients with substance dependence, clinicians should consider diagnostic assessments for gambling, as the co-occurrence of both disorders may impact clinical characteristics.