Age-related reduced prefrontal-amygdala structural connectivity is associated with lower trait anxiety

Neuropsychology. 2014 Jul;28(4):631-42. doi: 10.1037/neu0000060. Epub 2014 Mar 17.


Objective: A current neuroanatomical model of anxiety posits that greater structural connectivity between the amygdala and ventral prefrontal cortex (vPFC) facilitates regulatory control over the amygdala and helps reduce anxiety. However, some neuroimaging studies have reported contradictory findings, demonstrating a positive rather than negative association between trait anxiety and amygdala-vPFC white matter integrity. To help reconcile these findings, we tested the regulatory hypothesis of anxiety circuitry using aging as a model of white matter decline in the amygdala-vPFC pathway.

Methods: We used probabilistic tractography to trace connections between the amygdala and vPFC in 21 younger, 18 middle-aged, and 15 healthy older adults. The resulting tract estimates were used to extract 3 indices of white-matter integrity: fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). The relationship between these amygdala-vPFC structural connectivity measures and age and State-Trait Anxiety Inventory (STAI) scores were assessed.

Results: The tractography results revealed age-related decline in the FA (p = .005) and radial diffusivity (p = .002) of the amygdala-vPFC pathway. Contrary to the regulatory hypothesis, we found a positive rather than negative association between trait anxiety and right amygdala-vPFC FA (p = .01).

Conclusion: These findings argue against the notion that greater amygdala-vPFC structural integrity facilitates better anxiety outcomes in healthy adults. Instead, our results suggest that white matter degeneration in this network relates to lower anxiety in older adults.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging*
  • Amygdala / pathology*
  • Anisotropy
  • Anxiety / pathology*
  • Brain Mapping
  • Diffusion Magnetic Resonance Imaging
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Male
  • Middle Aged
  • Neural Pathways / pathology*
  • Prefrontal Cortex / pathology*
  • Psychiatric Status Rating Scales
  • Statistics, Nonparametric
  • White Matter / pathology
  • Young Adult