Autism-associated Nf1 deficiency disrupts corticocortical and corticostriatal functional connectivity in human and mouse
Autor: | Itamar Kahn, Roger J. Packer, Gil Zur, Alexandra Kavushansky, Eyal Bergmann, Shlomi Constantini, Maria T. Acosta, Noam Bosak, F. Xavier Castellanos, Ben Shofty, Gilbert Vezina, Liat Ben-Sira, Jad Asleh |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
Male
0301 basic medicine Cingulate cortex congenital hereditary and neonatal diseases and abnormalities Neurofibromatosis 1 Adolescent Autism Central nervous system Pediatric patients Striatum Biology Auditory cortex Article Mouse model lcsh:RC321-571 Mice 03 medical and health sciences 0302 clinical medicine Neural Pathways medicine Animals Humans ADHD Autistic Disorder Child neoplasms lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Default mode network fMRI Neuropsychology Brain Cognition medicine.disease Magnetic Resonance Imaging nervous system diseases Disease Models Animal 030104 developmental biology medicine.anatomical_structure Neurology Female Neuroscience 030217 neurology & neurosurgery Neurofibromatosis type 1 |
Zdroj: | Neurobiology of Disease, Vol 130, Iss, Pp 104479-(2019) Neurobiology of disease |
Popis: | 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. |
Databáze: | OpenAIRE |
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