Volumetric magnetic resonance and diffusion tensor imaging of C58/J mice: neural correlates of repetitive behavior
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ORIGINAL RESEARCH
Volumetric magnetic resonance and diffusion tensor imaging of C58/J mice: neural correlates of repetitive behavior Bradley J. Wilkes 1
&
Carly Bass 2 & Hannah Korah 2 & Marcelo Febo 2,3 & Mark H. Lewis 2,4
# Springer Science+Business Media, LLC, part of Springer Nature 2019
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. Keywords Repetitive behavior . Stereotypy . Basal ganglia . Cerebellum . Deformation-based morphometry . Diffusion tensor imaging
Introduction Restricted, repetitive behavior (RRB) involve seemingly purposeless patterns of behavior that exhibit little variation in form, interfere with appropriate behavior, and in some cases may even cause direct harm (e.g., self-injury). RRB * Bradley J. Wilkes [email protected] 1
Department of Applied Physiology and Kinesiology, University of Florida, Florida Gym, 1864 Stadium Road, P.O. Box 118205, Gainesville, FL 32611-8205, USA
2
Department of Psychiatry, McKnight Brain Institute, University of Florida, 1149 Newell Dr, Gainesville, FL 32611-2250, USA
3
Department of Neuroscience, McKnight Brain Institute, University of Florida, 1149 Newell Dr, Gainesville, FL 32611-2250, USA
4
Department of Psychology, University of Florida, Psychology Building, 945 Center Drive, P.O. Box 112250, Gainesville, FL 32611-2250, USA
encompasses a broad variety of behaviors, including motor stereotypies (e.g., hand-flapping or body-rocking), compulsions, rituals, and circumscribed interests (e.g., fixation on trains or electronic devices). RRB is present in a number of human conditio
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