Blunted activation in orbitofrontal cortex during mania: a functional magnetic resonance imaging study.
BACKGROUND
Patients with bipolar disorder have been reported to have abnormal cortical function during mania. In this study, we sought to investigate neural activity in the frontal lobe during mania, using functional magnetic resonance imaging (fMRI). Specifically, we sought to evaluate activation in the lateral orbitofrontal cortex, a brain region that is normally activated during activities that require response inhibition.


METHODS
Eleven manic subjects and 13 control subjects underwent fMRI while performing the Go-NoGo task, a neuropsychological paradigm known to activate the orbitofrontal cortex in normal subjects. Patterns of whole-brain activation during fMRI scanning were determined with statistical parametric mapping. Contrasts were made for each subject for the NoGo minus Go conditions. Contrasts were used in a second-level analysis with subject as a random factor.


RESULTS
Functional MRI data revealed robust activation of the right orbitofrontal cortex (Brodmann's area [BA] 47) in control subjects but not in manic subjects. Random-effects analyses demonstrated significantly less magnitude in signal intensity in the right lateral orbitofrontal cortex (BA 47), right hippocampus, and left cingulate (BA 24) in manic compared with control subjects.


CONCLUSIONS
Mania is associated with a significant attenuation of task-related activation of right lateral orbitofrontal function. This lack of activation of a brain region that is usually involved in suppression of responses might account for some of the disinhibition seen in mania. In addition, hippocampal and cingulate activation seem to be decreased. The relationship between this reduced function and the symptoms of mania remain to be further explored.
Altshuler
Lori L
LL
Department of Psychiatry, Los Angeles, California, USA. laltshuler@mednet.ucla.edu
Bookheimer
Susan Y
SY
Townsend
Jennifer
J
Proenza
Manuel A
MA
Eisenberger
Naomi
N
Sabb
Fred
F
Mintz
Jim
J
Cohen
Mark S
MS
D000328:Adult; D001714:Bipolar Disorder / Q000175:diagnosis / Q000503:physiopathology* / Q000523:psychology; D001931:Brain Mapping; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology*; D006179:Gyrus Cinguli / Q000503:physiopathology; D006801:Humans; D007266:Inhibition, Psychological; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data*; D008297:Male; D009483:Neuropsychological Tests; D011597:Psychomotor Performance / Q000502:physiology*; D011930:Reaction Time / Q000502:physiology; D012720:Severity of Illness Index; D013702:Temporal Lobe / Q000503:physiopathology