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Abstract #2237

Altered default mode network organization and functional connectivity in mice lacking autism-associated gene Shank3

Marco Pagani1,2, Camilla Robol1, Richard Gomolka1, Adam Liska1,2, Alberto Galbusera1, Anna Aksiuto1, and Alessandro Gozzi1

1Functional Neuroimaging Laboratory, Center for Neuroscience and Cognitive Systems, Istituto Italiano di Tecnologia, Rovereto, Italy, 2CIMeC, Center for Mind/Brain Sciences, University of Trento, Rovereto, Italy

Mutations in autism-associated gene Shank3 have been associated to alterations in striatal function and core autistic behaviors. However, the neocortical substrates affected by Shank3 mutations remain undetermined. By using structural and functional MRI in Shank3B mutant mice, we identified key alterations in prefrontal and associative regions of the mouse default mode network (DMN). Specifically, we show that prefrontal and antero-posterior areas of the DMN present decreased gray matter volume, an effect associated with reduced local and long-range prefrontal functional connectivity. Our findings suggest that Shank3 mutations may predispose to autism via a selective trophic and functional downregulation of prefrontal areas.

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