High motor variability in DYT1 dystonia is associated with impaired visuomotor adaptation

Anna Sadnicka,Anna Stevenson,Kailash P Bhatia,Mark J Edwards,Joseph M Galea,John C Rothwell

doi:10.1038/s41598-018-21545-0

Abstract

For the healthy motor control system, an essential regulatory role is maintaining the equilibrium between keeping unwanted motor variability in check whilst allowing informative elements of motor variability. Kinematic studies in children with generalised dystonia (due to mixed aetiologies) show that movements are characterised by increased motor variability. In this study, the mechanisms by which high motor variability may influence movement generation in dystonia were investigated. Reaching movements in the symptomatic arm of 10 patients with DYT1 dystonia and 12 age-matched controls were captured using a robotic manipulandum and features of motor variability were extracted. Given that task-relevant variability and sensorimotor adaptation are related in health, markers of variability were then examined for any co-variance with performance indicators during an error-based learning visuomotor adaptation task. First, we confirmed that motor variability on a trial-by-trial basis was selectively increased in the homogenous and prototypical dystonic disorder DYT1 dystonia. Second, high baseline variability predicted poor performance in the subsequent visuomotor adaptation task offering insight into the rules which appear to govern dystonic motor control. The potential mechanisms behind increased motor variability and its corresponding implications for the rehabilitation of patients with DYT1 dystonia are highlighted.

Highlights

Dystonia refers to an aetiologically diverse movement disorder characterised by involuntary muscle contractions[1]
We examined trial-by-trial variability of reaching movements in the symptomatic arm of 10 patients with DYT1 dystonia and 12 age-matched controls and explored the relationship between variability and performance in a visuomotor adaptation task
Abnormal reach behaviour in DYT1 dystonia demonstrated during baseline

Summary

Introduction

Dystonia refers to an aetiologically diverse movement disorder characterised by involuntary muscle contractions[1]. A popular example is that of young songbirds injecting ‘noise’ or variability into their song when the requirement is to optimise learning conditions, but immediately dampen such noise when high accuracy of song is required to perform to a potential mate[10,11] Such dynamic regulation of variability is observed in humans. We tested patients with DYT1 dystonia, an early onset generalised form of isolated dystonia caused by a single mutation in the TOR1A gene[14] With their homogenous genetic aetiology and ‘pure’ motor phenotype (no spasticity or other potentially confounding neurological deficits), we considered these patients an ideal group within which to examine quintessential abnormalities of motor control in dystonia[15]. Given that task-relevant variability and sensorimotor adaptation are related in health[12], an intriguing prediction is that DYT1 dystonia patients could show increased motor variability relative to healthy controls and enhanced learning during the adaptation task

Methods

Results

Conclusion