White matter integrity deficits in prefrontal-amygdala pathways in Williams syndrome

Suzanne N. Avery, Tricia A. Thornton-Wells, Adam W. Anderson, Jennifer Urbano Blackford

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Williams syndrome is a neurodevelopmental disorder associated with significant non-social fears. Consistent with this elevated non-social fear, individuals with Williams syndrome have an abnormally elevated amygdala response when viewing threatening non-social stimuli. In typically-developing individuals, amygdala activity is inhibited through dense, reciprocal white matter connections with the prefrontal cortex. Neuroimaging studies suggest a functional uncoupling of normal prefrontal-amygdala inhibition in individuals with Williams syndrome, which might underlie both the extreme amygdala activity and non-social fears. This functional uncoupling might be caused by structural deficits in underlying white matter pathways; however, prefrontal-amygdala white matter deficits have yet to be explored in Williams syndrome. We used diffusion tensor imaging to investigate prefrontal-amygdala white matter integrity differences in individuals with Williams syndrome and typically-developing controls with high levels of non-social fear. White matter pathways between the amygdala and several prefrontal regions were isolated using probabilistic tractography. Within each pathway, we tested for between-group differences in three measures of white matter integrity: fractional anisotropy (FA), radial diffusivity (RD), and parallel diffusivity (λ 1). Individuals with Williams syndrome had lower FA, compared to controls, in several of the prefrontal-amygdala pathways investigated, indicating a reduction in white matter integrity. Lower FA in Williams syndrome was explained by significantly higher RD, with no differences in λ 1, suggestive of lower fiber density or axon myelination in prefrontal-amygdala pathways. These results suggest that deficits in the structural integrity of prefrontal-amygdala white matter pathways might underlie the increased amygdala activity and extreme non-social fears observed in Williams syndrome.

Original languageEnglish (US)
Pages (from-to)887-894
Number of pages8
JournalNeuroImage
Volume59
Issue number2
DOIs
StatePublished - Jan 16 2012
Externally publishedYes

Keywords

  • Diffusion tensor imaging
  • Fear
  • Genetics
  • Neurodevelopmental disorders

ASJC Scopus subject areas

  • Neurology
  • Cognitive Neuroscience

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