Functional magnetic resonance imaging brain activation in bipolar mania: evidence for disruption of the ventrolateral prefrontal-amygdala emotional pathway.
BACKGROUND
Bipolar I disorder is defined by the occurrence of mania. The presence of mania, coupled with a course of illness characterized by waxing and waning of affective symptoms, suggests that bipolar disorder arises from dysfunction of neural systems that maintain emotional arousal and homeostasis. We used functional magnetic resonance imaging (fMRI) to study manic bipolar subjects as they performed a cognitive task designed to examine the ventrolateral prefrontal emotional arousal network.


METHODS
We used fMRI to study regional brain activation in 40 DSM-IV manic bipolar I patients and 36 healthy subjects while they performed a continuous performance task with emotional and neutral distracters. Event-related region-of-interest analyses were performed to test the primary hypothesis. Voxelwise analyses were also completed.


RESULTS
Compared with healthy subjects, the manic subjects exhibited blunted activation to emotional and neutral images, but not targets, across most of the predefined regions of interest. Several additional brain regions identified in the voxelwise analysis also exhibited similar differences between groups, including right parahippocampus, right lingual gyrus, and medial thalamus. In addition to these primary findings, the manic subjects also exhibited increased activation in response to targets in a number of brain regions that were primarily associated with managing affective stimuli. Group differences did not appear to be secondary to medication exposure or other confounds.


CONCLUSIONS
Bipolar manic subjects exhibit blunted brain fMRI response to emotional cues throughout the ventrolateral prefrontal emotional arousal network. Disruption of this emotional network may contribute to the mood dysregulation of bipolar disorder.
Division of Bipolar Disorders Research, Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0559. USA. Stephen.Strakowski@uc.edu
Stephen M
SM
Strakowski
James C
JC
Eliassen
Martine
M
Lamy
Michael A
MA
Cerullo
Jane B
JB
Allendorfer
Michelle
M
Madore
Jing-Huei
JH
Lee
Jeffrey A
JA
Welge
Melissa P
MP
DelBello
David E
DE
Fleck
Caleb M
CM
Adler
D000328:Adult; D000679:Amygdala / Q000503:physiopathology*; D001143:Arousal / Q000502:physiology; D001714:Bipolar Disorder / Q000503:physiopathology*; D001931:Brain Mapping; D004644:Emotions / Q000502:physiology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000503:physiopathology; D009434:Neural Pathways / Q000503:physiopathology; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000503:physiopathology*