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Current Opinions and Areas of Consensus on the Role of the Cerebellum in Dystonia

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Abstract

A role for the cerebellum in causing ataxia, a disorder characterized by uncoordinated movement, is widely accepted. Recent work has suggested that alterations in activity, connectivity, and structure of the cerebellum are also associated with dystonia, a neurological disorder characterized by abnormal and sustained muscle contractions often leading to abnormal maintained postures. In this manuscript, the authors discuss their views on how the cerebellum may play a role in dystonia. The following topics are discussed:

  • The relationships between neuronal/network dysfunctions and motor abnormalities in rodent models of dystonia.

  • Data about brain structure, cerebellar metabolism, cerebellar connections, and noninvasive cerebellar stimulation that support (or not) a role for the cerebellum in human dystonia.

  • Connections between the cerebellum and motor cortical and sub-cortical structures that could support a role for the cerebellum in dystonia.

Overall points of consensus include:

  • Neuronal dysfunction originating in the cerebellum can drive dystonic movements in rodent model systems.

  • Imaging and neurophysiological studies in humans suggest that the cerebellum plays a role in the pathophysiology of dystonia, but do not provide conclusive evidence that the cerebellum is the primary or sole neuroanatomical site of origin.

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Acknowledgments

VGS was supported by grants from the National Institutes of Health (K08NS072158, R01NS085054). EJH was supported in part by Public Health Service grant R01 NS088528 and a grant from the United States Department of Defense (PR140091). MSL was supported by grants from the National Institutes of Health (R01 NS069936, R01 NS082296, and Dystonia Coalition U54 NS065701), the Dorothy/Daniel Gerwin Parkinson’s Research Fund, and the Benign Essential Blepharospasm Research Foundation. HAJ was supported in part by a grant to the Dystonia Coalition (U54 NS065701, TR001456) from the Office of Rare Diseases at the National Center for Advancing Translational Studies and the National Institute of Neurological Disorders and Stroke at the NIH. MH was supported by the NIH intramural program. PLS was supported by grants from the National Institutes of Health (R01 NS24328, P30 NS076405, P40 OD010996). KK was supported by NIH grants NS050808 and NS079750.

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Authors and Affiliations

  1. Department of Neurology, University of Michigan, Room 4009, BSRB, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA

    Vikram G. Shakkottai & William T Dauer

  2. Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109-2200, USA

    Vikram G. Shakkottai

  3. Sobell Department of Motor Neuroscience and Movement Disorders, University College London, London, UK

    Amit Batla & Kailash Bhatia

  4. Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA

    William T Dauer

  5. Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, NY, USA

    Christian Dresel, Martin Niethammer & David Eidelberg

  6. Global Research Organization, Medtronic Inc. Neuromodulation, Minneapolis, MN, USA

    Robert S. Raike

  7. Yerkes National Primate Center and Department of Neurology, Emory University, Atlanta, GA, USA

    Yoland Smith

  8. Department of Neurology, Human Genetics and Pediatrics, Emory University, Atlanta, GA, USA

    H. A. Jinnah

  9. Departments of Pharmacology and Neurology, Emory University, Atlanta, GA, USA

    Ellen J. Hess

  10. Institut du Cerveau et de la Moelle épinière (ICM), Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR, S 1127, Paris, France

    Sabine Meunier

  11. Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA

    Sabine Meunier & Mark Hallett

  12. Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, NY, USA

    Rachel Fremont

  13. Dominick P. Purpura Department of Neuroscience, Department of Psychiatry and Behavioral Sciences, and The Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, New York, NY, USA

    Kamran Khodakhah

  14. Departments of Neurology, and Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN, USA

    Mark S. LeDoux

  15. Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013, Paris, France

    Traian Popa, Cécile Gallea & Stéphane Lehericy

  16. Centre de NeuroImagerie de Recherche – CENIR, ICM, F-75013, Paris, France

    Cécile Gallea

  17. Systems Neuroscience Institute and Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA, USA

    Andreea C. Bostan & Peter L. Strick

  18. Department of Neurobiology, University of Pittsburgh Brain Institute, University of Pittsburgh, Pittsburgh, PA, USA

    Peter L. Strick

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  1. Vikram G. Shakkottai
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  2. Amit Batla
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Correspondence to Vikram G. Shakkottai.

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Shakkottai, V.G., Batla, A., Bhatia, K. et al. Current Opinions and Areas of Consensus on the Role of the Cerebellum in Dystonia. Cerebellum 16, 577–594 (2017). https://doi.org/10.1007/s12311-016-0825-6

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