Research ArticleFUNCTIONAL NEUROIMAGING

Structural-functional connectivity deficits of neocortical circuits in the Fmr1−/y mouse model of autism

Science Advances  20 Nov 2015:
Vol. 1, no. 10, e1500775
DOI: 10.1126/sciadv.1500775

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Abstract

Fragile X syndrome (FXS), the most common inherited form of intellectual disability disorder and a frequent cause of autism spectrum disorder (ASD), is characterized by a high prevalence of sensory symptoms. Perturbations in the anatomical connectivity of neocortical circuits resulting in their functional defects have been hypothesized to contribute to the underlying etiology of these disorders. We tested this idea by probing alterations in the functional and structural connectivity of both local and long-ranging neocortical circuits in the Fmr1−/y mouse model of FXS. To achieve this, we combined in vivo ultrahigh-field diffusion tensor magnetic resonance imaging (MRI), functional MRI, and viral tracing approaches in adult mice. Our results show an anatomical hyperconnectivity phenotype for the primary visual cortex (V1), but a disproportional low connectivity of V1 with other neocortical regions. These structural data are supported by defects in the structural integrity of the subcortical white matter in the anterior and posterior forebrain. These anatomical alterations might contribute to the observed functional decoupling across neocortical regions. We therefore identify FXS as a “connectopathy,” providing a translational model for understanding sensory processing defects and functional decoupling of neocortical areas in FXS and ASD.

Keywords
  • Fragile X Syndrome
  • Autism
  • connectopathy
  • fMRI
  • DTI
  • retrograde tracing
  • neocortex
  • structural connectivity
  • functional connectivity
  • biomarker

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

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