Abnormally increased effective connectivity between parahippocampal gyrus and ventromedial prefrontal regions during emotion labeling in bipolar disorder

Abstract

Emotional liability and mood dysregulation characterize bipolar disorder (BD), yet no study has examined effective connectivity between parahippocampal gyrus and prefrontal cortical regions in ventromedial and dorsal/lateral neural systems subserving mood regulation in BD. Participants comprised 46 individuals (age range: 18-56 years): 21 with a DSM-IV diagnosis of BD, type I currently remitted; and 25 age- and gender-matched healthy controls (HC). Participants performed an event-related functional magnetic resonance imaging paradigm, viewing mild and intense happy and neutral faces. We employed dynamic causal modeling (DCM) to identify significant alterations in effective connectivity between BD and HC. Bayes model selection was used to determine the best model. The right parahippocampal gyrus (PHG) and right subgenual cingulate gyrus (sgCG) were included as representative regions of the ventromedial neural system. The right dorsolateral prefrontal cortex (DLPFC) region was included as representative of the dorsal/lateral neural system. Right PHG-sgCG effective connectivity was significantly greater in BD than HC, reflecting more rapid, forward PHG-sgCG signaling in BD than HC. There was no between-group difference in sgCG-DLPFC effective connectivity. In BD, abnormally increased right PHG-sgCG effective connectivity and reduced right PHG activity to emotional stimuli suggest a dysfunctional ventromedial neural system implicated in early stimulus appraisal, encoding and automatic regulation of emotion that may represent a pathophysiological functional neural mechanism for mood dysregulation in BD.

Figure 1. Proposed models for Bayes comparison in healthy controls and bipolar disorder patients

A) Model with simple forward connections between regions. B) Model with bilateral connection between PHG and sgCG; and simple forward connection between sgCG and DLPFC. C) Model with a forward connection between PHG and sgCG and a bilateral connection between sgCG and DLPFC. D) Model with bilateral connections between PHG and sgCG; and between sgCG and DLPFC. The most consistent model after the model comparison was a simple forward model (model A). PHG: Right parahippocampal gyrus; sgCG: Right subgenual cingulate gyrus; DLPFC: Right dorsolateral prefrontal cortex

Figure 2. Increased Effective connectivity between parahippocampal gyrus and ventromedial prefrontal regions during happy emotion labeling in bipolar disorder

PHG: Right parahippocampal gyrus; sgCG: right subgenual cingulate gyrus; DLPFC: right dorsolateral prefrontal cortex Red arrow: significantly greater positive effective connectivity in BD patients versus HC between right PHG and right sgCG (t(44)=2.15, p=0.037). Here, an increase in activity in the PHG “source” region was associated with an increase in activity in the sgCG “target” region Black arrow: non significant effective connectivity between subgenual cingulate gyrus and dorsolateral prefrontal cortex (t(44)=1.9, p=0.064).