title: 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.
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Jorge R C
authors.initials: JR
authors.lastname: Almeida
authors.forename: Andrea
authors.initials: A
authors.lastname: Mechelli
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hassel
authors.forename: Amelia
authors.initials: A
authors.lastname: Versace
authors.forename: David J
authors.initials: DJ
authors.lastname: Kupfer
authors.forename: Mary L
authors.initials: ML
authors.lastname: Phillips
mesh_terms: D000328:Adult; D001499:Bayes Theorem; D001714:Bipolar Disorder / Q000473:pathology* / Q000503:physiopathology*; D001931:Brain Mapping; D016022:Case-Control Studies; D004644:Emotions / Q000502:physiology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D015233:Models, Statistical; D009434:Neural Pathways; D009483:Neuropsychological Tests; D017711:Nonlinear Dynamics; D010100:Oxygen; D020534:Parahippocampal Gyrus / Q000098:blood supply / Q000503:physiopathology*; D017397:Prefrontal Cortex / Q000098:blood supply / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D010100:Oxygen