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Pathophysiology of Cerebellar Tremor: The Forward Model-Related Tremor and the Inferior Olive Oscillation-Related Tremor

Lesions in the Guillain–Mollaret (G–M) triangle frequently cause various types of tremors or tremor-like movements. Nevertheless, we know relatively little about their generation mechanisms. The deep cerebellar nuclei (DCN), which is a primary node of the triangle, has two main output paths: the pri...

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Autores principales: Kakei, Shinji, Manto, Mario, Tanaka, Hirokazu, Mitoma, Hiroshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273235/
https://www.ncbi.nlm.nih.gov/pubmed/34262527
http://dx.doi.org/10.3389/fneur.2021.694653
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author Kakei, Shinji
Manto, Mario
Tanaka, Hirokazu
Mitoma, Hiroshi
author_facet Kakei, Shinji
Manto, Mario
Tanaka, Hirokazu
Mitoma, Hiroshi
author_sort Kakei, Shinji
collection PubMed
description Lesions in the Guillain–Mollaret (G–M) triangle frequently cause various types of tremors or tremor-like movements. Nevertheless, we know relatively little about their generation mechanisms. The deep cerebellar nuclei (DCN), which is a primary node of the triangle, has two main output paths: the primary excitatory path to the thalamus, the red nucleus (RN), and other brain stem nuclei, and the secondary inhibitory path to the inferior olive (IO). The inhibitory path contributes to the dentato-olivo-cerebellar loop (the short loop), while the excitatory path contributes to the cerebrocerebellar loop (the long loop). We propose a novel hypothesis: each loop contributes to physiologically distinct type of tremors or tremor-like movements. One type of irregular tremor-like movement is caused by a lesion in the cerebrocerebellar loop, which includes the primary path. A lesion in this loop affects the cerebellar forward model and deteriorates its accuracy of prediction and compensation of the feedback delay, resulting in irregular instability of voluntary motor control, i.e., cerebellar ataxia (CA). Therefore, this type of tremor, such as kinetic tremor, is usually associated with other symptoms of CA such as dysmetria. We call this type of tremor forward model-related tremor. The second type of regular tremor appears to be correlated with synchronized oscillation of IO neurons due, at least in animal models, to reduced degrees of freedom in IO activities. The regular burst activity of IO neurons is precisely transmitted along the cerebellocerebral path to the motor cortex before inducing rhythmical reciprocal activities of agonists and antagonists, i.e., tremor. We call this type of tremor IO-oscillation-related tremor. Although this type of regular tremor does not necessarily accompany ataxia, the aberrant IO activities (i.e., aberrant CS activities) may induce secondary maladaptation of cerebellar forward models through aberrant patterns of long-term depression (LTD) and/or long-term potentiation (LTP) of the cerebellar circuitry. Although our hypothesis does not cover all tremors or tremor-like movement disorders, our approach integrates the latest theories of cerebellar physiology and provides explanations how various lesions in or around the G–M triangle results in tremors or tremor-like movements. We propose that tremor results from errors in predictions carried out by the cerebellar circuitry.
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spelling pubmed-82732352021-07-13 Pathophysiology of Cerebellar Tremor: The Forward Model-Related Tremor and the Inferior Olive Oscillation-Related Tremor Kakei, Shinji Manto, Mario Tanaka, Hirokazu Mitoma, Hiroshi Front Neurol Neurology Lesions in the Guillain–Mollaret (G–M) triangle frequently cause various types of tremors or tremor-like movements. Nevertheless, we know relatively little about their generation mechanisms. The deep cerebellar nuclei (DCN), which is a primary node of the triangle, has two main output paths: the primary excitatory path to the thalamus, the red nucleus (RN), and other brain stem nuclei, and the secondary inhibitory path to the inferior olive (IO). The inhibitory path contributes to the dentato-olivo-cerebellar loop (the short loop), while the excitatory path contributes to the cerebrocerebellar loop (the long loop). We propose a novel hypothesis: each loop contributes to physiologically distinct type of tremors or tremor-like movements. One type of irregular tremor-like movement is caused by a lesion in the cerebrocerebellar loop, which includes the primary path. A lesion in this loop affects the cerebellar forward model and deteriorates its accuracy of prediction and compensation of the feedback delay, resulting in irregular instability of voluntary motor control, i.e., cerebellar ataxia (CA). Therefore, this type of tremor, such as kinetic tremor, is usually associated with other symptoms of CA such as dysmetria. We call this type of tremor forward model-related tremor. The second type of regular tremor appears to be correlated with synchronized oscillation of IO neurons due, at least in animal models, to reduced degrees of freedom in IO activities. The regular burst activity of IO neurons is precisely transmitted along the cerebellocerebral path to the motor cortex before inducing rhythmical reciprocal activities of agonists and antagonists, i.e., tremor. We call this type of tremor IO-oscillation-related tremor. Although this type of regular tremor does not necessarily accompany ataxia, the aberrant IO activities (i.e., aberrant CS activities) may induce secondary maladaptation of cerebellar forward models through aberrant patterns of long-term depression (LTD) and/or long-term potentiation (LTP) of the cerebellar circuitry. Although our hypothesis does not cover all tremors or tremor-like movement disorders, our approach integrates the latest theories of cerebellar physiology and provides explanations how various lesions in or around the G–M triangle results in tremors or tremor-like movements. We propose that tremor results from errors in predictions carried out by the cerebellar circuitry. Frontiers Media S.A. 2021-06-28 /pmc/articles/PMC8273235/ /pubmed/34262527 http://dx.doi.org/10.3389/fneur.2021.694653 Text en Copyright © 2021 Kakei, Manto, Tanaka and Mitoma. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Kakei, Shinji
Manto, Mario
Tanaka, Hirokazu
Mitoma, Hiroshi
Pathophysiology of Cerebellar Tremor: The Forward Model-Related Tremor and the Inferior Olive Oscillation-Related Tremor
title Pathophysiology of Cerebellar Tremor: The Forward Model-Related Tremor and the Inferior Olive Oscillation-Related Tremor
title_full Pathophysiology of Cerebellar Tremor: The Forward Model-Related Tremor and the Inferior Olive Oscillation-Related Tremor
title_fullStr Pathophysiology of Cerebellar Tremor: The Forward Model-Related Tremor and the Inferior Olive Oscillation-Related Tremor
title_full_unstemmed Pathophysiology of Cerebellar Tremor: The Forward Model-Related Tremor and the Inferior Olive Oscillation-Related Tremor
title_short Pathophysiology of Cerebellar Tremor: The Forward Model-Related Tremor and the Inferior Olive Oscillation-Related Tremor
title_sort pathophysiology of cerebellar tremor: the forward model-related tremor and the inferior olive oscillation-related tremor
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273235/
https://www.ncbi.nlm.nih.gov/pubmed/34262527
http://dx.doi.org/10.3389/fneur.2021.694653
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