Regional brain changes in bipolar I depression: A functional magnetic resonance imaging study

Lori Altshuler, Susan Bookheimer, Jennifer Townsend, Manuel A. Proenza, Fred Sabb, Jim Mintz, Mark S. Cohen

Research output: Contribution to journalArticlepeer-review

111 Scopus citations


Objective: To investigate neural activity in prefrontal cortex and amygdala during bipolar depression. Methods: Eleven bipolar I depressed and 17 normal subjects underwent functional magnetic resonance imaging (fMRI) while performing a task known to activate prefrontal cortex and amygdala. Whole brain activation patterns were determined using statistical parametric mapping (SPM) when subjects matched faces displaying neutral or negative affect (match condition) or matched a geometric form (control condition). Contrasts for each group for the match versus control conditions were used in a second-level random effects analysis. Results: Random effects between-group analysis revealed significant attenuation in right and left orbitofrontal cortex (BA47) and right dorsolateral prefrontal cortex (DLPFC) (BA9) in bipolar depressed subjects. Additionally, random effects analysis showed a significantly increased activation in left lateral orbitofrontal cortex (BA10) in the bipolar depressed versus control subjects. Within-group contrasts demonstrated significant amygdala activation in the controls and no significant amygdala activation in the bipolar depressed subjects. The amygdala between-group difference, however, was not significant. Conclusions: Bipolar depression is associated with attenuated bilateral orbitofrontal (BA47) activation, attenuated right DLPFC (BA9) activation and heightened left orbitofrontal (BA10) activation. BA47 attenuation has also been reported in mania and may thus represent a trait feature of the disorder. Increased left prefrontal (BA10) activation may be a state marker to bipolar depression. Our findings suggest dissociation between mood-dependent and disease-dependent functional brain abnormalities in bipolar disorder.

Original languageEnglish (US)
Pages (from-to)708-717
Number of pages10
JournalBipolar disorders
Issue number6
StatePublished - 2008
Externally publishedYes


  • Amygdala
  • Bipolar depression
  • Bipolar disorder
  • Functional magnetic resonance imaging
  • Orbitofrontal cortex

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


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