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The Role of the Cerebellum in Repetitive Behavior Across Species: Childhood Stereotypies and Deer Mice

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Abstract

Recent studies suggest that the cerebellum may have a significant role in repetitive behaviors. In primary complex motor stereotypies, typically developing children have repetitive movements usually involving rhythmic flapping/waving arm/hand movements. Similarly, the deer mouse animal model exhibits inherited repetitive behaviors, with increased frequencies of spontaneous jumping and rearing. In this study, data from both children with motor stereotypies and deer mice were used to investigate the role of the cerebellum in repetitive behaviors. The 3.0-T MRI volumetric imaging of the cerebellum was obtained in 20 children with primary complex motor stereotypies and 20 healthy controls. In deer mice, cerebellar volume (n = 7/group) and cell counts (n = 9/group) were compared between high- and low-activity animals. Levels of cerebellar neurotransmitters were also determined via HPLC (n = 10/group). In children with stereotypies, (a) there were a statistically significant reduction (compared to controls) in the white matter volume of the posterior cerebellar lobule VI–VII that negatively correlated with motor control and (b) an 8% increase in the anterior vermis gray matter that positively correlated with motor Stereotypy Severity Scores (SSS). In deer mice, (a) there was a significant increase in the volume of the anterior vermal granular cell layer that was associated with higher activity and (b) dentate nucleus cell counts were higher in high activity animals. Similar increases in volume were observed in anterior vermis in children with stereotypies and a deer mouse model of repetitive behaviors. These preliminary findings support the need for further investigation of the cerebellum in repetitive behaviors.

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Acknowledgements

We wish to thank Joshua Wilhide, Maggie LaCourse, and all the other staff members of Molecular Characterization and Analysis Complex (MCAC) at the University of Maryland Baltimore County (UMBC) for their superb support in neurochemical quantification process. Thanks to Dr. Nae-Yuh Wang for the statistical expertise. Figure 5 is adapted from SMART-Servier Medical Art and is provided for use free of charge under Creative Commons.

Funding

This work was supported by philanthropic gifts to the Johns Hopkins Motor Stereotypy Research Initiative Fund from the Nesbitt-McMaster Foundation, Klump Family, and Graves Family. This publication was also made possible by the Johns Hopkins Institute for Clinical and Translational Research (ICTR) which is funded in part by Grant Number UL1 TR003098 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research and the Kennedy Krieger Institute’s IDDRC Grant Number P50 HD103538.

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Authors and Affiliations

  1. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Shannon L. Dean, Laura Tochen, Farhan Augustine, Syed F. Ali, Shreenath Rajendran, Mary E. Blue, E. Mark Mahone & Harvey S. Singer

  2. Department of Neurology, Kennedy Krieger Institute, Baltimore, MD, 21205, USA

    Shannon L. Dean, Deana Crocetti, Mary E. Blue, Stewart H. Mostofsky & Harvey S. Singer

  3. Department of Neurology, Children’s National Hospital, Washington, DC, USA

    Laura Tochen

  4. University of Maryland, Baltimore County, Baltimore, MD, USA

    Farhan Augustine

  5. Department of Neurology, New York Medical College, Valhalla, NY, USA

    Syed F. Ali

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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Shannon Dean, Laura Tochen, Farhan Augustine, Shreenath Rajendran, and Syed F. Ali. The first draft of the manuscript was written by Shannon Dean, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Shannon L. Dean.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Johns Hopkins Investigational Review Board (IRB). Informed consent was obtained from all individual participants included in the study.

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One author, Shreenath Rajendran, is now employed by Mitokinin, Inc. This company was not involved in the research for this article and the contents do not necessarily reflect the official views of Mitokinin Inc.

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Dean, S.L., Tochen, L., Augustine, F. et al. The Role of the Cerebellum in Repetitive Behavior Across Species: Childhood Stereotypies and Deer Mice. Cerebellum 21, 440–451 (2022). https://doi.org/10.1007/s12311-021-01301-3

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