AbstractThe Iowa Gambling Task (IGT) is a sensitive test for the detection of decision‐making impairments in several neurological and psychiatric populations. Very few studies have employed the IGT in functional magnetic resonance imaging (fMRI) investigations, in part, because the task is cognitively complex. Here we report a method for exploring brain activity using fMRI during performance of the IGT. Decision‐making during the IGT was associated with activity in several brain regions in a group of healthy individuals. The activated regions were consistent with the neural circuitry hypothesized to underlie somatic marker activation and decision‐making. Specifically, a neural circuitry involving the dorsolateral prefrontal cortex (for working memory), the insula and posterior cingulate cortex (for representations of emotional states), the mesial orbitofrontal and ventromedial prefrontal cortex (for coupling the two previous processes), the ventral striatum and anterior cingulate/SMA (supplementary motor area) for implementing behavioral decisions was engaged. These results have implications for using the IGT to study abnormal mechanisms of decision making in a variety of clinical populations. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.