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      Consensus Paper: Experimental Neurostimulation of the Cerebellum

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          Abstract

          The cerebellum is best known for its role in controlling motor behaviors. However, recent work supports the view that it also influences non-motor behaviors. The contribution of the cerebellum towards different brain functions is underscored by its involvement in a diverse and increasing number of neurological and neuropsychiatric conditions including ataxia, dystonia, essential tremor, Parkinson’s disease (PD), epilepsy, stroke, multiple sclerosis, autism spectrum disorders, dyslexia, attention deficit hyperactivity disorder (ADHD), and schizophrenia. Although there are no cures for these conditions, cerebellar stimulation is quickly gaining attention for symptomatic alleviation, as cerebellar circuitry has arisen as a promising target for invasive and non-invasive neuromodulation. This consensus paper brings together experts from the fields of neurophysiology, neurology, and neurosurgery to discuss recent efforts in using the cerebellum as a therapeutic intervention. We report on the most advanced techniques for manipulating cerebellar circuits in humans and animal models and define key hurdles and questions for moving forward.

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          Parallel organization of functionally segregated circuits linking basal ganglia and cortex.

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            Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing.

            Patients with cerebellar damage often present with the cerebellar motor syndrome of dysmetria, dysarthria and ataxia, yet cerebellar lesions can also result in the cerebellar cognitive affective syndrome (CCAS), including executive, visual spatial, and linguistic impairments, and affective dysregulation. We have hypothesized that there is topographic organization in the human cerebellum such that the anterior lobe and lobule VIII contain the representation of the sensorimotor cerebellum; lobules VI and VII of the posterior lobe comprise the cognitive cerebellum; and the posterior vermis is the anatomical substrate of the limbic cerebellum. Here we analyze anatomical, functional neuroimaging, and clinical data to test this hypothesis. We find converging lines of evidence supporting regional organization of motor, cognitive, and limbic behaviors in the cerebellum. The cerebellar motor syndrome results when lesions involve the anterior lobe and parts of lobule VI, interrupting cerebellar communication with cerebral and spinal motor systems. Cognitive impairments occur when posterior lobe lesions affect lobules VI and VII (including Crus I, Crus II, and lobule VIIB), disrupting cerebellar modulation of cognitive loops with cerebral association cortices. Neuropsychiatric disorders manifest when vermis lesions deprive cerebro-cerebellar-limbic loops of cerebellar input. We consider this functional topography to be a consequence of the differential arrangement of connections of the cerebellum with the spinal cord, brainstem, and cerebral hemispheres, reflecting cerebellar incorporation into the distributed neural circuits subserving movement, cognition, and emotion. These observations provide testable hypotheses for future investigations. Copyright (c) 2009 Elsevier Srl. All rights reserved.
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              Response of brain tissue to chronically implanted neural electrodes.

              Chronically implanted recording electrode arrays linked to prosthetics have the potential to make positive impacts on patients suffering from full or partial paralysis. Such arrays are implanted into the patient's cortical tissue and record extracellular potentials from nearby neurons, allowing the information encoded by the neuronal discharges to control external devices. While such systems perform well during acute recordings, they often fail to function reliably in clinically relevant chronic settings. Available evidence suggests that a major failure mode of electrode arrays is the brain tissue reaction against these implants, making the biocompatibility of implanted electrodes a primary concern in device design. This review presents the biological components and time course of the acute and chronic tissue reaction in brain tissue, analyses the brain tissue response of current electrode systems, and comments on the various material science and bioactive strategies undertaken by electrode designers to enhance electrode performance.
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                Author and article information

                Contributors
                832-824-8913 , sillitoe@bcm.edu
                Journal
                Cerebellum
                Cerebellum
                Cerebellum (London, England)
                Springer US (New York )
                1473-4222
                1473-4230
                4 June 2019
                4 June 2019
                2019
                : 18
                : 6
                : 1064-1097
                Affiliations
                [1 ]GRID grid.416975.8, ISNI 0000 0001 2200 2638, Department of Pathology and Immunology, Department of Neuroscience, Program in Developmental Biology, Baylor College of Medicine, , Jan and Dan Duncan Neurological Research Institute of Texas Children’s Hospital, ; 1250 Moursund Street, Suite 1325, Houston, TX 77030 USA
                [2 ]GRID grid.239578.2, ISNI 0000 0001 0675 4725, Neurological Institute, Department of Neurosurgery, , Cleveland Clinic, ; 9500 Euclid Avenue, Cleveland, OH 44195 USA
                [3 ]GRID grid.9654.e, ISNI 0000 0004 0372 3343, Department of Exercise Science, Faculty of Science, , University of Auckland, ; Private Bag 92019, Auckland, 1142 New Zealand
                [4 ]GRID grid.168010.e, ISNI 0000000419368956, Department of Neurosurgery, , Stanford University School of Medicine, ; 1201 Welch Road, MSLS P352, Stanford, CA 94305-5487 USA
                [5 ]GRID grid.189967.8, ISNI 0000 0001 0941 6502, Department of Neurology, , Emory University, ; Atlanta, GA 30322 USA
                [6 ]GRID grid.5645.2, ISNI 000000040459992X, Department of Neuroscience, , Erasmus Medical Center, ; 3015 AA Rotterdam, Netherlands
                [7 ]Human Motor Control Section, NINDS, NIH, Building 10, Room 7D37, 10 Center Dr MSC 1428, Bethesda, MD 20892-1428 USA
                [8 ]GRID grid.267301.1, ISNI 0000 0004 0386 9246, Department of Anatomy and Neurobiology, , University of Tennessee Health Science Center, ; 855 Monroe Ave, Memphis, TN 38163 USA
                [9 ]GRID grid.7692.a, ISNI 0000000090126352, NIDOD Department, Wilhelmina Children’s Hospital, , University Medical Center Utrecht Brain Center, ; Utrecht, Netherlands
                [10 ]GRID grid.1021.2, ISNI 0000 0001 0526 7079, School of Engineering, , Deakin University, ; Geelong, VIC 3216 Australia
                [11 ]GRID grid.21729.3f, ISNI 0000000419368729, Department of Neurology, College of Physicians and Surgeons, , Columbia University, ; New York, NY 10032 USA
                [12 ]GRID grid.47100.32, ISNI 0000000419368710, Department of Neurology, Yale School of Medicine, Department of Chronic Disease Epidemiology, Yale School of Public Health, Center for Neuroepidemiology and Clinical Research, Yale School of Medicine, , Yale University, ; New Haven, CT 06520 USA
                [13 ]GRID grid.413871.8, ISNI 0000 0001 0124 3248, Service de Neurologie, , CHU-Charleroi, ; 6000 Charleroi, Belgium
                [14 ]GRID grid.8364.9, ISNI 0000 0001 2184 581X, Service des Neurosciences, , Université de Mons, ; 7000 Mons, Belgium
                [15 ]GRID grid.117476.2, ISNI 0000 0004 1936 7611, Graduate School of Health, Physiotherapy, , University of Technology Sydney, ; PO Box 123, Broadway, Sydney, NSW 2007 Australia
                [16 ]GRID grid.419241.b, ISNI 0000 0001 2285 956X, Department of Psychology and Neurosiences, , Leibniz Research Centre for Working Environment and Human Factors, ; Dortmund, Germany
                [17 ]Department of Neurology, University Medical Hospital Bergmannsheil, Bochum, Germany
                [18 ]GRID grid.50545.31, ISNI 0000000406089296, Service de Neurochirurgie, , CHU Saint-Pierre, ; 1000 Bruxelles, Belgium
                [19 ]GRID grid.5333.6, ISNI 0000000121839049, Defitech Chair of Clinical Neuroengineering, Center for Neuroprosthetics (CNP) and Brain Mind Institute (BMI), , Ecole Polytechnique Federale de Lausanne (EPFL), ; Sion, Switzerland
                [20 ]GRID grid.39158.36, ISNI 0000 0001 2173 7691, Department of Physiology, , Hokkaido University School of Medicine, ; Sapporo, 060-8638 Japan
                [21 ]GRID grid.5718.b, ISNI 0000 0001 2187 5445, Department of Neurology, University Hospital Essen, , University of Duisburg-Essen, ; Essen, Germany
                [22 ]GRID grid.266102.1, ISNI 0000 0001 2297 6811, R281 Department of Neurosurgery, , Stanfod University School of Medicine, ; 300 Pasteur Drive, Stanford, CA 94305 USA
                [23 ]GRID grid.189967.8, ISNI 0000 0001 0941 6502, Yerkes National Primate Research Center, , Emory University, ; Atlanta, GA 30322 USA
                [24 ]GRID grid.170205.1, ISNI 0000 0004 1936 7822, Department of Neurology, , University of Chicago, ; 5841 S. Maryland Avenue, MC 2030, Chicago, IL 60637-1470 USA
                Article
                1041
                10.1007/s12311-019-01041-5
                6867990
                31165428
                c3b541a1-e692-4150-87da-33c7d8ea7b82
                © The Author(s) 2019

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100009633, Eunice Kennedy Shriver National Institute of Child Health and Human Development;
                Award ID: U54HD083092
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000065, National Institute of Neurological Disorders and Stroke;
                Award ID: R01NS089664
                Award ID: K08 NS083738
                Award ID: R01 NS094607
                Award ID: R01 NS085136
                Award ID: R01 NS073872
                Award ID: R01 NS088257
                Award Recipient :
                Funded by: National Institute of Neurological Disorders and Stroke (US)
                Award ID: R01NS100874
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: R01-NS062876
                Award ID: P50-NS098685
                Award Recipient :
                Funded by: NIH Office of Research Infrastructure Programs
                Award ID: OD P51-OD011132
                Award Recipient :
                Funded by: FNRS Belgium
                Funded by: Louis V. Gerstner Jr. Scholar Award
                Funded by: Parkinson’s Foundation
                Award ID: N/A
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100008447, International Essential Tremor Foundation;
                Funded by: MEXT
                Award ID: 25119005
                Award ID: 17H03539
                Award ID: 18H05523
                Award Recipient :
                Funded by: Mercator Research Center Ruhr
                Award ID: Pr-2015-0019
                Award ID: Pr-2015-0019
                Award Recipient :
                Funded by: German Research Fourndation
                Award ID: SFB1280 TP A05
                Award Recipient :
                Funded by: German Research Fourndation
                Award ID: SFB1280 TP A06
                Award Recipient :
                Funded by: American Parkinson’s Disease Association Advanced Center for Parkinson’s Research
                Award ID: N/A
                Award ID: N/A
                Award Recipient :
                Funded by: Michael J. Fox Foundation for Parkinson's Research (US)
                Award ID: N/A
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                Funded by: FundRef http://dx.doi.org/10.13039/100006483, AbbVie;
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                Funded by: FundRef http://dx.doi.org/10.13039/100002491, Bristol-Myers Squibb;
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                Funded by: FundRef http://dx.doi.org/10.13039/100005614, Biogen;
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                Award Recipient :
                Funded by: Bucksbaum Institute for Clinical Excellence (US)
                Award ID: N/A
                Award Recipient :
                Funded by: Claire O'Neil Essential Tremor Research Fund
                Award ID: N/A
                Award Recipient :
                Funded by: National Institutes of Mental Health
                Award ID: R01MH112143
                Award Recipient :
                Funded by: National Institutes of Mental Health
                Award ID: R01MH112143
                Award Recipient :
                Categories
                Consensus Paper
                Custom metadata
                © Springer Science+Business Media, LLC, part of Springer Nature 2019

                Neurology
                cerebellum,neurostimulation,neuromodulation,dbs,non-invasive therapy,optogenetics
                Neurology
                cerebellum, neurostimulation, neuromodulation, dbs, non-invasive therapy, optogenetics

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