Abnormal cerebellar connectivity and plasticity in isolated cervical dystonia.

Giacomo Koch,Robert Chen,Pablo Mir,Juan Francisco Martín-Rodríguez,Paolo Porcacchia,Francisco J Palomar,Paloma Álvarez De Toledo,Antonio Rodríguez-Baena,Laura Vargas-González,Silvia Jesús

doi:10.1371/journal.pone.0211367

Abstract

There is increasing evidence that supports the role of the cerebellum in the pathophysiology of dystonia. We used transcranial magnetic stimulation to test the hypothesis that patients with cervical dystonia may have a disrupted cerebellar cortical connectivity at rest, and that cerebellar plasticity is altered too. We enrolled 12 patients with isolated cervical dystonia and 13 controls. A paired-pulse transcranial magnetic stimulation protocol was applied over the right cerebellum and the left primary motor area. Changes in the amplitude of motor evoked potentials were analysed. Continuous and intermittent Theta Burst Stimulation over the cerebellum was also applied. The effects of these repetitive protocols on cortical excitability, on intra-cortical circuits and on cerebellar cortical inhibition were analysed. In healthy subjects, but not in dystonic patients, a conditioning stimulus over the cerebellum was able to inhibit the amplitude of the motor evoked potentials from primary motor cortex. In healthy subjects continuous and intermittent cerebellar Theta Burst Stimulation were able to decrease and increase respectively motor cortex excitability. Continuous Theta Burst Stimulation was able to abolish the cerebellar cortical inhibition observed in basal condition. These effects were not observed in patients with cervical dystonia. Cerebellar cortical connectivity and cerebellar plasticity is altered at rest in patients with cervical dystonia.

Highlights

The involvement of the cerebellum in the pathophysiology of dystonia is a concept that has emerged over the last few years
We studied the effects of cerebellar iTBS of the lateral cerebellum on motor evoked potential (MEP), short intracortical inhibition/facilitation (SICI-intra-cortical facilitation (ICF)) and cerebellar cortical inhibition (CBI) circuits
The present study focuses the attention on the cerebellum and on its role in cervical dystonia

Summary

Introduction

The involvement of the cerebellum in the pathophysiology of dystonia is a concept that has emerged over the last few years. The same definition of isolated dystonia excludes cerebellar signs on clinical examination, it is well known that the cerebellum is involved in some forms of secondary dystonia [1] and that patients with degenerative cerebellar disorders can present dystonia as part of the clinical phenotype [2]. 0741/2010, PI-0437-2012, PI-0471/2013), the Sociedad Andaluza de Neurologıa, the Fundacion Alicia Koplowitz, the Fundacion Mutua Madrileña and the Jaques and Gloria Gossweiler Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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Results

Conclusion