Differential activation of the anterior cingulate cortex and caudate nucleus in persons with a family history of alcoholism during a gambling simulation: Studies from the Oklahoma Family Health Patterns Project

Individuals with a family history of alcoholism (FH+) are at enhanced risk of developing an alcohol or other substance use disorder relative to those without this history (FH-). Recent studies comparing FH+ and FH- individuals have revealed differences in cognition, emotion processing, sociability, and decision-making. These differences suggest possible altered brain functioning in FH+ individuals that may play a crucial role in vulnerability to substance use disorders. In the present study, 15 FH + and 19 FH- individuals performed the IGT, a simulated card game requiring integration of payoff-to-penalty ratios, while undergoing functional magnetic resonance imaging. All participants performed the task more conservatively as the session progressed, and the FH groups achieved similar payoffs by the end of the game. Imaging revealed a distributed network of brain regions that was engaged when subjects performed this task, including the right inferior frontal and postcentral gyri, left parahippocampal gyrus, insula and precuneous cortices, left inferior and superior parietal lobules, left lentiform nucleus and bilateral culmen, claustrum, lingual gyri and cerebellar tonsils. Despite a lack of behavioral differences between groups, the FH+ participants showed significantly more activation in the left dorsal anterior cingulate cortex and left caudate nucleus. These findings correspond to models of risk in FH+ persons that postulate biases in brain decision-making systems as underlying elevated risk for alcoholism. inhibitory activation, despite a lack of behavioral differences. Glahn and colleagues (2007) found FH+ individuals with high behavioral undercontrol showed decreased amygdala (BOLD) activation in response to faces displaying negative emotions compared to FH- individuals with low behavioral undercontrol. These findings suggest that systematic exploration of cerebral function in relation to appropriate behavioral challenges may yield useful information about at-risk populations. The present study was designed to compare BOLD activation differences in FH+ and FH-individuals performing the Iowa Gambling Task (IGT) (Bechara et al., 1997; Bechara et al., 2001) to better understand differences in neural functioning and recruitment associated with FH+. The IGT is a simulated card game that requires subjects to track response outcomes in relation to making safe vs. risky choices. Performance on this task involves cognitive processes such as working memory, set shifting, and risk-taking; and these processes appear to be subtly altered in FH+ individuals (Deckel, 1999; Dunn et al., 2006; Lovallo, 2006). Previously, it was found there were no overall differences in the proportion of safe vs. risky choices FH+ and FH-made on this task, although further analysis indicated FH+ males choices were slightly more influenced by gains on previous trials (Lovallo et al., 2006). Given that several FH relevant cognitive processes are involved with the IGT and the expected lack of overall performance differences between FH+ and FH- individuals, we reasoned the this task would be useful assay for exploring differences in neural functioning between FH+ and FH-individuals. We predicted that the FH+ and FH- individuals would show differences in task-induced forebrain cortical and subcortical regions. We suspected that differences would be seen in prefrontal regions associated with decision-making and possibly in limbic areas associated with processing reward value of outcomes.