Study Links “Neuroflexibility” of Ventromedial Prefrontal Cortex With Stress Resilience

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Researchers investigate the neural processes involved in coping during stress.

The range of traumatic and stressful experiences some individuals are able to endure suggests that they possess a remarkable capacity for resilient coping, though the underlying neural processes are unclear. Active coping strategies such as the use of reappraisal and reframing have been linked with resilience and positive health outcomes, while maladaptive coping — via suppression, avoidance, and rumination, for example — has been associated with negative health outcomes. In a new study published in the Proceedings of the National Academy of Sciences, scientists at Yale University School of Medicine aimed to shed light on the mechanisms involved in acute stress reactivity, adaptation, and active coping.

Based on extensive evidence that the ventromedial prefrontal cortex (VmPFC) is closely associated with adaptive coping, the researchers hypothesized that it is “one of the critical loci of neuroplasticity in a resilience-coping network that signals increased emotional and behavioral control,” and active stress coping. To assess the neural processes associated with both the stress response and active coping, a sample of 30 young adults with no previous physical or psychiatric disorders underwent functional magnetic resonance imaging (fMRI) during “brief successive exposure to a block of highly aversive images… that were compared with a no-stress, neutral control block involving nonaversive neutral images…” according to the study.

Following each 60-second run of images (5 seconds per image with a 1-second break in between for a total of 10 images per run), participants gave subjective stress and arousal ratings, and their plasma cortisol levels and heart rate were assessed intermittently and continually, respectively

For the stress vs neutral blocks, the investigators identified the following:

  • Sustained increases in subjective stress (condition main effect, F(1,29) = 894.91, P <.0001) and arousal (condition main effect, F(1,29) = 198.12, P < 0.0001) ratings
  • Increased average heart rate (condition main effect, F(1,28) = 4.51, P <.03)
  • Increased plasma cortisol response (condition main effect, F(1,26) = 3.73, P = .05)
  • Increased neural activity in cortico-limbic striatal regions, including the hypothalamus, amygdala, hippocampus, thalamus, ventral and dorsal striatum, insula and midtemporal regions, dorsal anterior cingulate cortex, dorsolateral prefrontal cortex (DLPFC), and the midbrain regions [P <.05 whole brain corrected (WBC); large effect sizes over 1.0)
  • Significant VmPFC deactivation and increased activity in the ventrolateral prefrontal regions (VLPFC) (P < 0.05, WBC)

The observed increases in the amygdala, striatum, hypothalamus, midbrain, right insula, and right DLPFC regions “supported the stress processing and reactivity circuit,” reported the authors. “Second, dynamic neural activation during stress vs neutral runs, showing early increases followed by later reduced activation in the VLPFC, dorsal anterior cingulate cortex, left DLPFC, hippocampus, and left insula suggested a stress adaptation response network,” they wrote.

Finally, the hypoactivity and subsequent increased activation of the VmPFC highlights this area as a critical locus of emotional and behavioral control. In line with this, reduced VmPFC activity predicted a greater number of maladaptive real-life coping behaviors, such as binge alcohol drinking and emotional eating. Overall, the findings suggest that neuroplasticity of the VmPFC is key to resilient coping during stress.


Sinha R, Lacadie CM, Constable RT, Seo D. Dynamic neural activity during stress signals resilient coping. Proc Natl Acad Sci USA. 2016 Jul 18. doi: 10.1073/pnas.1600965113 [Epub ahead of print]

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