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

• Type of Material: Article
• Authors: Vikram Shakkottai, University of Michigan; Amit Batla, College London; Kailash Bhatia, College London; William T. Dauer, University of Michigan; Christian Dresel, The Feinstein Institute for Medical Research; Martin Niethammer, The Feinstein Institute for Medical Research; David Eidelberg, The Feinstein Institute for Medical Research; Robert S. Raike, Medtronic Inc.; Yoland Smith, Emory University; Hyder A Jinnah, Emory University; Ellen Hess, Emory University; Sabine Meunier, Institut du Cerveau et de la Moelle épinière; Mark Hallett, National Institute of Neurological Disorders and Stroke; Rachel Fremont, Albert Einstein College of Medicine; Kamran Khodakhah, Albert Einstein College of Medicine; Mark S. LeDoux, University of Tennessee; Traian Popa, Institut du Cerveau et de la Moelle épinière; Cecile Gallea, Institut du Cerveau et de la Moelle épinière; Stephane Lehericy, Institut du Cerveau et de la Moelle épinière; Andreea C. Bostan, University of Pittsburgh; Peter L. Strick, University of Pittsburgh
• Language: English
• Date: 2017-04-01
• Publisher: Springer Verlag (Germany)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016, Springer Science+Business Media New York.
• Final Published Version (URL): http://dx.doi.org/10.1007/s12311-016-0825-6
• Title of Journal or Parent Work: Cerebellum
• ISSN: 1473-4222
• Volume: 16
• Issue: 2
• Start Page: 577
• End Page: 594
• Grant/Funding Information: PLS was supported by grants from the National Institutes of Health (R01 NS24328, P30 NS076405, P40 OD010996).; 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.; KK was supported by NIH grants NS050808 and NS079750.; EJH was supported in part by Public Health Service grant R01 NS088528 and a grant from the United States Department of Defense (PR140091).; MH was supported by the NIH intramural program.; VGS was supported by grants from the National Institutes of Health (K08NS072158, R01NS085054).; 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.
• Keywords: PURKINJE-CELL ACTIVITY; Science & Technology; THETA BURST STIMULATION; Neurosciences & Neurology; Networks; Ataxia; Life Sciences & Biomedicine; DYT1; KNOCK-IN MOUSE; DEEP BRAIN-STIMULATION; Dystonia; PRIMARY TORSION DYSTONIA; Neurosciences; EPISODIC ATAXIA TYPE-2; MOTOR CORTEX PLASTICITY; DOPA-RESPONSIVE DYSTONIA; FOCAL HAND DYSTONIA; Circuits; Cerebellum; BENIGN ESSENTIAL BLEPHAROSPASM
• Research Categories: Biology, Neuroscience; Biology, Genetics; Health Sciences, Pharmacology

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.