Brain systems underlying response flexibility in healthy and bipolar adolescents: an event-related fMRI study

Previous studies have indicated abnormalities in response flexibility in pediatric bipolar disorder (BD). Dysfunction in response flexibility may contribute to the pattern of behavioral and emotional dysregulation that is characteristic of BD, since depressed and manic patients respond inflexibly to emotional stimuli (i.e., anhedonia in the case of depression or inappropriate positive affect in the case of mania). The present study was undertaken to determine if neuronal responses differed between BD and control subjects on a simple motor response flexibility task. To elucidate the neural substrates mediating response flexibility in pediatric BD, we studied 25 youth with BD and 17 age-, gender- and IQ-matched controls (CON) as they performed the change task while undergoing event-related functional magnetic resonance imaging (fMRI). The change task is a new fMRI task that requires subjects to both inhibit and replace a prepotent motor response with another motor response after the initial response has been cued. On correctly performed change trials relative to correctly performed go trials, BD patients generated significantly more activity in the left dorsolateral prefrontal cortex (DLPFC) and in the primary motor cortex than did healthy controls, even though performance levels did not differ across groups. These results indicate that functional deficits within the left DLPFC may mediate deficits in response flexibility in pediatric BD. This deficit may extend beyond the realm of motor control and also affect emotion regulation.