In this manuscript, research articles using functional magnetic resonance imaging (fMRI) to study adult patients with bipolar disorder were reviewed. The findings from these studies identify altered brain activation in five regions in cortico-limbic pathways responsible for emotional regulation: portions of the prefrontal cortex; anterior cingulate cortex; amygdala; thalamus; and striatum. The most consistent findings were overactivation of amygdala, striatum, and thalamus. Findings in prefrontal cortex were less consistent, but most studies also showed increased activation in ventrolateral and dorsolateral prefrontal cortical areas. Excessive activation in brain regions associated with emotional regulation may contribute to the affective symptoms of bipolar disorder. However, there are several important limitations in this body of research. Even when similar tasks were used, brain activation was often discrepant among studies. Most fMRI studies examined small samples (ten or fewer bipolar subjects) limiting statistical power. Additionally, most studies were confounded by patients taking psychotropic medications. Nonetheless, from this work an anterior limbic over-activation model of bipolar disorder is emerging.
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