Distinct regions of prefrontal cortex mediate resistance and vulnerability to depression

Michael Koenigs, Edward D. Huey, Matthew Calamia, Vanessa Raymont, Daniel Tranel, Jordan Grafman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

167 Scopus citations


The neuroanatomical correlates of depression remain unclear. Functional imaging data have associated depression with abnormal patterns of activity in prefrontal cortex (PFC), including the ventromedial (vmPFC) and dorsolateral (dlPFC) sectors. If vmPFC and dlPFC are critical neural substrates for the pathogenesis of depression, then damage to either area should affect the expression of depressive symptoms. Using patients with brain lesions we show that, relative to nonfrontal lesions, bilateral vmPFC lesions are associated with markedly low levels of depression, whereas bilateral dorsal PFC lesions (involving dorsomedial and dorsolateral areas in both hemispheres) are associated with substantially higher levels of depression. These findings demonstrate that vmPFC and dorsal PFC are critically and causally involved in depression, although with very different roles: vmPFC damage confers resistance to depression, whereas dorsal PFC damage confers vulnerability.

Original languageEnglish (US)
Pages (from-to)12341-12348
Number of pages8
JournalJournal of Neuroscience
Issue number47
StatePublished - Nov 19 2008


  • Depression
  • Dorsolateral
  • Emotion
  • Neuropathology
  • Prefrontal cortex
  • Ventromedial

ASJC Scopus subject areas

  • Neuroscience(all)


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