RT Journal Article
SR Electronic
T1 Loss of function in the autism and learning disabilities associated gene <em>Nf1</em> disrupts corticocortical and corticostriatal functional connectivity in human and mouse
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 618223
DO 10.1101/618223
A1 Ben Shofty
A1 Eyal Bergmann
A1 Gil Zur
A1 Jad Asleh
A1 Noam Bosak
A1 Alexandra Kavushansky
A1 F. Xavier Castellanos
A1 Liat Ben-Sira
A1 Roger J. Packer
A1 Gilbert L. Vezina
A1 Shlomi Constantini
A1 Maria T. Acosta
A1 Itamar Kahn
YR 2019
UL http://biorxiv.org/content/early/2019/04/26/618223.abstract
AB Children with the autosomal dominant single gene disorder, neurofibromatosis type 1 (NF1), display multiple structural and functional changes in the central nervous system, resulting in neuropsychological cognitive abnormalities. Here we assessed the pathological functional organization that may underlie the behavioral impairments in NF1 using resting-state functional connectivity MRI. Coherent spontaneous fluctuations in the fMRI signal across the entire brain were used to interrogate the pattern of functional organization of corticocortical and corticostriatal networks in both NF1 pediatric patients and mice with a heterozygous mutation in the Nf1 gene (Nf1+/-). Children with NF1 demonstrated abnormal organization of cortical association networks and altered posterior-anterior functional connectivity in the default network. Examining the contribution of the striatum revealed that corticostriatal functional connectivity was altered. NF1 children demonstrated reduced functional connectivity between striatum and the frontoparietal network and increased striatal functional connectivity with the limbic network. Awake passive mouse functional connectivity MRI in Nf1+/- mice similarly revealed reduced posterior-anterior connectivity along the cingulate cortex as well as disrupted corticostriatal connectivity. The striatum of Nf1+/- mice showed increased functional connectivity to somatomotor and frontal cortices and decreased functional connectivity to the auditory cortex. Collectively, these results demonstrate similar alterations across species, suggesting that NF1 pathogenesis is linked to striatal dysfunction and disrupted corticocortical connectivity in the default network.