During a fearful face perception task, patients with bipolar disorder showed a significantly different pattern of early-versus late-stage changes in BOLD signal relative to healthy controls. These differences suggest that in the early stage of the task, there were minimal group differences in whole brain activation, but over the course of the task, normal control subjects showed significant late-stage increases within the orbitofrontal cortex and striatum. Bipolar patients did not show this pattern. Instead they showed greater late-stage activation across a distributed network of posterior cortical and subcortical brain regions typically associated with perceptual and memory processes. Statistical comparison between the groups at this latter stage of the task suggest that bipolar patients showed significantly less task-related activation than controls within the putamen, caudate, anterior cingulate gyrus, orbitofrontal cortex, and superior temporal pole, regions that have been implicated in affective processing and its modulation [20
], although these were not evident at a more stringent corrected threshold. Together, these findings suggest that during multiple presentations of faces expressing fear, healthy subjects show progressive activation of striatal regions involved in emotion-based learning and motivational control [22
], possibly reflecting a process of affective-motivational-behavioral adaptation whereby affective information is learned and integrated with ongoing motivational routines to prepare the individual for appropriate action [11
]. Conversely, bipolar patients failed to show this pattern, instead activating diffuse cortical areas involved in visual perception, memory encoding and recall, facial perception, and visceral sensation. Thus, these findings provide further evidence for a dysfunction within the fronto-striatal circuitry in patients with bipolar disorder [2
Inspection of the ROI time-course plots clearly shows abnormal BOLD signal responses in the basal ganglia and amygdala in the bipolar group relative to the healthy controls. Whereas controls showed notable changes in signal intensity in both ROIs that coincided with the onset and offset of the stimuli, particularly during the second block, bipolar patients failed to show these task related increases in either ROI. The interaction between diagnostic group and stimulus Block was significant for the amygdala, suggesting that bipolar patients failed to show the increase in responsiveness upon later exposure to the emotional stimuli exhibited by the controls. Other possible differences between diagnostic groups, such as anticipatory activation and delayed offset of initial responses in the patient group were visually apparent, but these will require further research to substantiate. It remains unknown whether such response patterns are correlated with behavioral and cognitive features of bipolar disorder.
As with any study of actively medicated patients, these data are limited by potential differences in medication type, dosage, and current clinical state among the patients. Attempts were made to control for these factors at intake and by selecting only patients during their first psychiatric admission. Furthermore, due to the selection of only first admission patients, it is possible that there was some diagnostic heterogeneity in the sample that will only be evident longitudinally. It is also important to note that these findings should be considered as preliminary, as the whole brain activation was evaluated at an uncorrected height threshold of p < .001 and none of the whole brain imaging comparisons between diagnostic groups survived correction for multiple comparisons. Finally, this sample was small and will require replication. With due consideration given to these limitations, however, the present findings provide compelling preliminary evidence that first episode bipolar patients differ from healthy controls in the time-course of responsiveness of key affect processing regions to facial expressions of fear.