title: Structural-functional connectivity deficits of neocortical circuits in the Fmr1 (-/y) mouse model of autism.
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.
authors.affiliation: INSERM, Neurocentre Magendie, Physiopathologie de la plasticité neuronale, U862, 33077 Bordeaux, France. ; University of Bordeaux, Neurocentre Magendie, Physiopathologie de la plasticité neuronale, U862, 33076 Bordeaux, France. ; Institute of NeuroInformatics, University of Zurich, 8057 Zurich, Switzerland.
authors.forename: Matthias G
authors.identifier: 0000-0002-4961-7832
authors.initials: MG
authors.lastname: Haberl
authors.affiliation: Biomedical MR Research Group, Department of Radiology and Nuclear Medicine, Radboud University Medical Center, 6500 Nijmegen, Netherlands.
authors.forename: Valerio
authors.initials: V
authors.lastname: Zerbi
authors.affiliation: Biomedical MR Research Group, Department of Radiology and Nuclear Medicine, Radboud University Medical Center, 6500 Nijmegen, Netherlands.
authors.forename: Andor
authors.initials: A
authors.lastname: Veltien
authors.affiliation: INSERM, Neurocentre Magendie, Physiopathologie de la plasticité neuronale, U862, 33077 Bordeaux, France. ; University of Bordeaux, Neurocentre Magendie, Physiopathologie de la plasticité neuronale, U862, 33076 Bordeaux, France.
authors.forename: Melanie
authors.initials: M
authors.lastname: Ginger
authors.affiliation: Biomedical MR Research Group, Department of Radiology and Nuclear Medicine, Radboud University Medical Center, 6500 Nijmegen, Netherlands.
authors.forename: Arend
authors.identifier: 0000-0001-9930-4562
authors.initials: A
authors.lastname: Heerschap
authors.affiliation: INSERM, Neurocentre Magendie, Physiopathologie de la plasticité neuronale, U862, 33077 Bordeaux, France. ; University of Bordeaux, Neurocentre Magendie, Physiopathologie de la plasticité neuronale, U862, 33076 Bordeaux, France.
authors.forename: Andreas
authors.initials: A
authors.lastname: Frick
keywords: Autism; DTI; Fragile X Syndrome; biomarker; connectopathy; fMRI; functional connectivity; neocortex; retrograde tracing; structural connectivity