Functional MRI of sustained attention in bipolar mania

We examined sustained attention deficits in bipolar disorder and associated changes in brain activation assessed by functional magnetic resonance imaging (fMRI). We hypothesized that relative to healthy participants, those with mania or mixed mania would (1) exhibit incremental decrements in sustained attention over time, (2) overactivate brain regions required for emotional processing and (3) progressively underactivate attentional regions of prefrontal cortex. Fifty participants with manic/mixed bipolar disorder (BP group) and 34 healthy comparison subjects (HC group) received an fMRI scan while performing a 15-min continuous performance task (CPT). The data were divided into three consecutive 5-min vigilance periods to analyze sustained attention. Composite brain activation maps indicated that both groups activated dorsal and ventral regions of an anterior-limbic network, but the BP group exhibited less activation over time relative to baseline. Consistent with hypotheses 1 and 2, the BP group showed a marginally greater behavioral CPT sustained attention decrement and more bilateral amygdala activation than the HC group, respectively. Instead of differential activation in prefrontal cortex over time, as predicted in hypothesis 3, the BP group progressively decreased activation in subcortical regions of striatum and thalamus relative to the HC group. These results suggest that regional activation decrements in dorsolateral prefrontal cortex accompany sustained attention decrements in both bipolar and healthy individuals. Stable amygdala overactivation across prolonged vigils may interfere with sustained attention and exacerbate attentional deficits in bipolar disorder. Differential striatal and thalamic deactivation in bipolar disorder is interpreted as a loss of amygdala (emotional brain) modulation by the ventrolateral prefrontal-subcortical circuit, which interferes with attentional maintenance.