Functional and Structural Connectivity Between the Perigenual Anterior Cingulate and Amygdala in Bipolar Disorder

Objective: Abnormalities in the morphology and function of two gray matter structures central to emotional processing, the perigenual anterior cingulate cortex (pACC) and amygdala, have consistently been reported in bipolar disorder (BD). Evidence implicates abnormalities in their connectivity in BD. This study investigates the potential disruptions in pACC-amygdala functional connectivity and associated abnormalities in white matter that provides structural connections between the two brain regions in BD. Methods: Thirty-three individuals with BD and 31 healthy comparison subjects (HC) participated in a scanning session during which functional magnetic resonance imaging (fMRI) during processing of face stimuli and diffusion tensor imaging (DTI) were performed. The strength of pACC-amygdala functional connections was compared between BD and HC groups, and associations between these functional connectivity measures from the fMRI scans and regional fractional anisotropy (FA) from the DTI scans were assessed. Results: Functional connectivity was decreased between the pACC and amygdala in the BD group compared with HC group, during the processing of fearful and happy faces (p < .005). Moreover, a significant positive association between pACC-amygdala functional coupling and FA in ventrofrontal white matter, including the region of the uncinate fasciculus, was identified (p < .005). Conclusion: This study provides evidence for abnormalities in pACC-amygdala functional connectivity during emotional processing in BD. The significant association between pACC-amygdala functional connectivity and the structural integrity of white matter that contains pACC-amygdala connections suggest that disruptions in white matter connectivity may contribute to disturbances in the coordinated responses of the pACC and amygdala during emotional processing in BD.

National Institute of Mental Health (NIH)[R01MH69747]

National Institute of Mental Health (NIH)

National Institute of Mental Health (NIH)

National Institute of Mental Health (NIH)[R01MH070902]

National Institute of Mental Health (NIH)[T32MH1427G]

National Institute of Mental Health (NIH)

Clinical and Translational Science Award (CTSA), NIH National Center[UL1 RR0249139]

Clinical and Translational Science Award (CTSA), NIH National Center

Department of Veterans Affairs Career Development (HPB), Merit Review (HPB) and Research Enhancement Award Program (REAP)

Department of Veterans Affairs Career Development (HPB), Merit Review (HPB) and Research Enhancement Award Program (REAP)

National Alliance for Research in Schizophrenia and Depression (Great Neck, New York)

National Alliance for Research in Schizophrenia and Depression (Great Neck, New York)

Attias Family Foundation

Attias Family Foundation

Marcia Simon Kaplan

Marcia Simon Kaplan

Ethel F. Donaghzre Women`s Investigator Program

Ethel F. Donaghzre Women`s Investigator Program

Klingenstein Foundation

Klingenstein Foundation

Howard Hughes Medical Institute Fellowship

Howard Hughes Medical Institute Fellowship