Bipolar mood state reflected in cortico-amygdala resting state connectivity: A cohort and longitudinal study

Abstract

Background: Using resting-state functional magnetic resonance imaging (rsfMRI), we previously compared cohorts of bipolar I subjects in a manic state to those in a euthymic state to identify mood state-specific patterns of cortico-amygdala connectivity. Our results suggested that mania is reflected in the disruption of emotion regulation circuits. We sought to replicate this finding in a group of subjects with bipolar disorder imaged longitudinally across states of mania and euthymia METHODS: We divided our subjects into three groups: 26 subjects imaged in a manic state, 21 subjects imaged in a euthymic state, and 10 subjects imaged longitudinally across both mood states. We measured differences in amygdala connectivity between the mania and euthymia cohorts. We then used these regions of altered connectivity to examine connectivity in the longitudinal bipolar group using a within-subjects design.

Results: Our findings in the mania vs euthymia cohort comparison were replicated in the longitudinal analysis. Bipolar mania was differentiated from euthymia by decreased connectivity between the amygdala and pre-genual anterior cingulate cortex. Mania was also characterized by increased connectivity between amygdala and the supplemental motor area, a region normally anti-correlated to the amygdala in emotion regulation tasks.

Limitations: Stringent controls for movement effects limited the number of subjects in the longitudinal sample.

Conclusions: In this first report of rsfMRI conducted longitudinally across mood states, we find that previously observed between-group differences in amygdala connectivity are also found longitudinally within subjects. These results suggest resting state cortico-amygdala connectivity is a biomarker of mood state in bipolar disorder.

Keywords: Bipolar; Connectivity; FMRI; Imaging; Longitudinal.

Figure 1. Whole-brain changes in functional connectivity to the right amygdala in bipolar mania compared to euthymia

1.A The right amygdala demonstrates increased functional connectivity to the bilateral SMA in mania compared to euthymia (R: peak coordinates x21, y3, z66, T-stat 4.11, extent k=47 voxels. L: coordinates x-21, y6, z69, T-stat 4.12, extent =78 voxels). The color bar indicates T-statistic magnitude. Images are thresholded at voxel-wise P<.005. This region of significantly increased connectivity is shown projected onto a MNI152 template brain at the y=3 and z=69 levels. 1.B The right amygdala demonstrates decreased functional connectivity to the pre-genual ACC in bipolar mania compared to bipolar euthymia (peak coordinates x3, y45, z0, T-stat 4.25, extent = 201 voxels). The color bar indicates T-statistic magnitude. Images are thresholded at voxel-wise P<.005. This region of significantly decreased connectivity is shown projected onto a MNI152 template brain at the x=0 and z=0 levels.