Abstract
Restricted, repetitive behavior (RRB) involves sequences of responding with little variability and no obvious function. RRB is diagnostic for autism spectrum disorder (ASD) and a significant feature in several neurodevelopmental disorders. Despite its clinical importance, relatively little is known about how RRB is mediated by broader neural circuits. In this study, we employed ultra-high field (17.6 Tesla) magnetic resonance imaging (MRI) to study the C58/J mouse model of RRB. We determined alterations in brain morphology and connectivity of C58/J mice and their relationship to repetitive motor behavior using structural MRI and diffusion tensor imaging (DTI). Compared to the genetically similar C57BL/6 control mouse strain, C58/J mice showed evidence of structural alterations in basal ganglia and cerebellar networks. In particular, C58/J mice exhibited reduced volumes of key cortical and basal ganglia regions that have been implicated in repetitive behavior, including motor cortex, striatum, globus pallidus, and subthalamic nucleus, as well as volume differences in the cerebellum. Moreover, DTI revealed differences in fractional anisotropy and axial diffusivity in cerebellar white matter of C58/J mice. Importantly, we found that RRB exhibited by C58/J mice was correlated with volume of the striatum, subthalamic nucleus, and crus II of the cerebellum. These regions are key nodes in circuits connecting the basal ganglia and cerebellum and our findings implicate their role in RRB, particularly the indirect pathway.
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Acknowledgements
The authors thank Dr. Luis M. Colon-Perez for assistance with preparing and testing the pulse sequence parameters for anatomical and diffusion imaging at 17.6 Tesla. Authors acknowledge support from the National High Magnetic Field Laboratory’s Advanced Magnetic Resonance Imaging & Spectroscopy (AMRIS) Facility (National Science Foundation Cooperative Agreement No. DMR-1157490 and the State of Florida)..
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Research reported in this publication was supported by the National Center For Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR001427. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work was also supported by the American Psychological Association Dissertation Research Award [AGR DTD 12-14-2016].
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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All animal procedures performed in this study were approved by the Institutional Animal Care and Use Committee at the University of Florida. This article does not contain any studies with human participants performed by any of the authors.
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Wilkes, B.J., Bass, C., Korah, H. et al. Volumetric magnetic resonance and diffusion tensor imaging of C58/J mice: neural correlates of repetitive behavior. Brain Imaging and Behavior 14, 2084–2096 (2020). https://doi.org/10.1007/s11682-019-00158-9
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DOI: https://doi.org/10.1007/s11682-019-00158-9