Several studies have implicated the involvement of two major components of emotion regulatory networks, the ventrolateral prefrontal cortex (VLPFC) and amygdala, in the pathophysiology of bipolar disorder. In healthy subjects, the VLPFC has been shown to negatively modulate amygdala response when subjects cognitively evaluate an emotional face by identifying and labeling the emotion it expresses. The current study used such a paradigm to assess whether the strength of this modulation was altered in bipolar subjects when manic. During functional magnetic resonance imaging (fMRI), nine manic subjects with bipolar I disorder and nine healthy subjects either named the emotion shown in a face by identifying one of two words that correctly expressed the emotion (emotion labeling task) or matched the emotion shown in a face to one of two other faces (emotion perception task). The degree to which the VLPFC regulated amygdala response during these tasks was assessed using a psychophysiological interaction (PPI) analysis. Compared with healthy subjects, manic patients had a significantly reduced VLPFC regulation of amygdala response during the emotion labeling task. These findings, taken in context with previous fMRI studies of bipolar mania, suggest that reductions in inhibitory frontal activity in these patients may lead to an increased reactivity of the amygdala.

The proportionality of blood oxygen level-dependent (BOLD) response during a cognitive task and that from a hypercapnic challenge was investigated in cortical structures involved in working memory (WM). Breath holding (BH) following inspiration was used to induce a BOLD response characteristic of regional vasomotor reactivity but devoid of metabolic changes. BOLD effects measured during BH were used to normalize individual subject activations during WM, which effectively reduced the confounding influence of individual- and region-specific differences in hemodynamic responsivity common to both tasks. In a study of seven subjects, the BH calibration reduced intersubject variability in WM effect amplitude by 24.8% (P < 0.03). Reduced intersubject variability resulted in a 23.7% increase in group WM activation voxel extent significant at P < 0.001, with further increases at more stringent thresholds. Because the BH task does not require CO(2) inhalation or other invasive manipulations and is broadly applicable across cortical regions, the proposed approach is simple to implement and may be beneficial for use not only in quantitative group fMRI analyses, but also for multicenter and longitudinal studies.

Previous structural neuroimaging studies of bipolar disorder have reported conflicting findings in limbic structures. Medication heterogeneity of patient samples may have contributed to these inconsistencies. Using structural magnetic resonance imaging we assessed whether lithium treatment was associated with differences in amygdala and hippocampal volumes in a sample of bipolar adults. A total of 49 magnetic resonance imaging scans were collected from patients who were currently treated with or without lithium. Amygdala and hippocampal volumes were analyzed using tensor-based morphometry. Statistical between-group comparisons of deformation maps showed that patients treated with lithium exhibited significantly increased volumes of the amygdala and hippocampus compared with patients who were not taking lithium. Our findings may help to explain previous inconsistencies in the bipolar literature.