Ventromedial prefrontal cortex is critical for the regulation of amygdala activity in humans

Biol Psychiatry. 2015 Feb 1;77(3):276-284. doi: 10.1016/j.biopsych.2014.02.014. Epub 2014 Feb 26.


Background: Dysfunction in the ventromedial prefrontal cortex (vmPFC) is believed to play a pivotal role in the pathogenesis of mood and anxiety disorders. Leading neurocircuitry models of these disorders propose that hypoactivity in the vmPFC engenders disinhibited activity of the amygdala and, consequently, pathologically elevated levels of negative affect. This model predicts that a selective loss or diminution of function of the vmPFC would result in heightened activity of the amygdala. Although this prediction has been borne out in rodent lesion and electrophysiologic studies using fear conditioning and extinction paradigms, there has not yet been a definitive test of this prediction in humans.

Methods: We tested this prediction through a novel use of functional magnetic resonance imaging in four neurosurgical patients with focal, bilateral vmPFC damage.

Results: Relative to neurologically healthy comparison subjects, the patients with vmPFC lesions exhibited potentiated amygdala responses to aversive images and elevated resting-state amygdala functional connectivity. No comparable group differences were observed for activity in other brain regions.

Conclusions: These results provide unique evidence for the critical role of the vmPFC in regulating activity of the amygdala in humans and help elucidate the causal neural interactions that underlie mental illness.

Keywords: Amygdala; Anxiety; Emotion; Lesion; Prefrontal cortex; fMRI.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amygdala / physiology*
  • Brain Mapping
  • Cerebrovascular Circulation / physiology
  • Emotions / physiology
  • Female
  • Heart Rate
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neural Pathways / physiopathology
  • Neuropsychological Tests
  • Oxygen / blood
  • Photic Stimulation
  • Photoplethysmography
  • Prefrontal Cortex / physiopathology*
  • Prefrontal Cortex / surgery
  • Rest
  • Visual Perception / physiology


  • Oxygen