Our results support a hypothesis that defects in ventral medial frontal processing lead to impaired decisions that involve risk. Reductions in right prefrontal activity during decision-making appear to be modulated by the presence of gambling problems and may reflect impaired working memory, stimulus reward valuation, or cue reactivity in substance-dependent individuals.

Background-The neurobiological underpinnings of bipolar disorder are not well understood. Previous neuroimaging findings have been inconsistent; however, new methods for threedimensional (3-D) computational image analysis may better characterize neuroanatomic changes than standard volumetric measures.

Background-Chronic exposure to drugs of addiction induces cellular adaptations in orbitofrontal cortex (OFC) and associated limbic-prefrontal pathways that may underlie abuse-related behavior. A propensity to make risky decisions in spite of substantial negative consequences may be mediated by medial OFC dysfunction in substance dependent individuals (SDI). We tested the hypothesis that medial OFC gray matter (GM) volume would be lower in SDI compared to controls.

BackgroundAdolescents with conduct and substance problems (“Antisocial Substance Disorder” (ASD)) repeatedly engage in risky antisocial and drug-using behaviors. We hypothesized that, during processing of risky decisions and resulting rewards and punishments, brain activation would differ between abstinent ASD boys and comparison boys.Methodology/Principal FindingsWe compared 20 abstinent adolescent male patients in treatment for ASD with 20 community controls, examining rapid event-related blood-oxygen-level-dependent (BOLD) responses during functional magnetic resonance imaging. In 90 decision trials participants chose to make either a cautious response that earned one cent, or a risky response that would either gain 5 cents or lose 10 cents; odds of losing increased as the game progressed. We also examined those times when subjects experienced wins, or separately losses, from their risky choices. We contrasted decision trials against very similar comparison trials requiring no decisions, using whole-brain BOLD-response analyses of group differences, corrected for multiple comparisons. During decision-making ASD boys showed hypoactivation in numerous brain regions robustly activated by controls, including orbitofrontal and dorsolateral prefrontal cortices, anterior cingulate, basal ganglia, insula, amygdala, hippocampus, and cerebellum. While experiencing wins, ASD boys had significantly less activity than controls in anterior cingulate, temporal regions, and cerebellum, with more activity nowhere. During losses ASD boys had significantly more activity than controls in orbitofrontal cortex, dorsolateral prefrontal cortex, brain stem, and cerebellum, with less activity nowhere.Conclusions/SignificanceAdolescent boys with ASD had extensive neural hypoactivity during risky decision-making, coupled with decreased activity during reward and increased activity during loss. These neural patterns may underlie the dangerous, excessive, sustained risk-taking of such boys. The findings suggest that the dysphoria, reward insensitivity, and suppressed neural activity observed among older addicted persons also characterize youths early in the development of substance use disorders.

The objective of this study was to test the hypothesis that 4 weeks of lithium administration would be associated with changes in brain gray and white matter volumes in healthy individuals. Thirteen right-handed healthy volunteers (6 females, mean age = 25.9 ± 10.0 y) were studied. 3D SPGR MRIs (TR = 25ms, TE = 5ms, slice-thickness = 1.5mm) were acquired using a 1.5 T GE Signa Imaging System, at baseline and after 4 weeks of lithium administration at therapeutically relevant doses. Optimized voxel based morphometry (VBM) analyses were conducted. Left and right dorsolateral prefrontal cortex and left anterior cingulate gray matter volumes increased significantly following lithium administration. Total white matter volume was increased, whereas total brain volume and total gray matter volume were not significantly changed following 4 weeks of lithium. Lithium treatment resulted in prefrontal regional gray matter volume increases in healthy volunteers, as well as increases in total white matter volume. Whether these changes are mediated by neurotrophic/ neuroprotective or osmotic effects remains unknown.