OBJECTIVES: Clinical and regulatory acceptance of upcoming molecular treatments in degenerative ataxias might greatly benefit from ecologically valid endpoints which capture change in ataxia severity in patients real life. This longitudinal study aimed to unravel quantitative motor biomarkers in degenerative ataxias in real life turning movements which are sensitive for changes both longitudinally and at the preataxic stage. METHODS: Combined cross-sectional (n=30) and longitudinal (n=14, 1 year interval) observational study in degenerative cerebellar disease (including 8 pre-ataxic mutation carriers) compared to 23 healthy controls. Turning movements were assessed by three body-worn inertial sensors in three conditions: (1) instructed laboratory assessment, (2) supervised free walking, and (3) unsupervised real-life movements. RESULTS: Measures which quantified dynamic balance during turning, lateral velocity change (LVC) and outward acceleration, but not general turning measures such as speed, allowed differentiating ataxic against healthy subjects in real life with high effect size (δ=0.68), with LVC also differentiating preataxic against healthy subjects (δ=0.53). LVC was highly correlated with clinical ataxia severity (SARA score, effect size ρ=0.79) and subjective balance confidence (ABC score, ρ=0.66). Moreover, LVC in real life but not general turning measures, gait measures, or the SARA score allowed detecting significant longitudinal change in one-year follow-up with high effect size (rprb=0.66). CONCLUSIONS: Measures of turning allow to capture specific changes of dynamic balance in degenerative ataxia in real life, with high sensitivity to longitudinal differences in ataxia severity and to the preataxic stage. They thus present promising ecologically valid motor biomarkers for capturing change in real life, even in the highly treatment-relevant early stages of degenerative cerebellar disease.

In this paper, we present learning-based methods for the analysis of the spatio-temporal characteristics of multi-dimensional movement trajectories. We show the application of these methods in two studies analyzing the influence of the cerebellum on intra-limb coordination and adaptation of gait for cerebellar patients

A b s t r a c t BACKGROUND: With disease-modifying drugs on the horizon for degenerative ataxias,

Predicting the behavior of objects in the environment is an important requirement to overcome latencies in the sensorimotor system and realize precise actions in rapid situations. Internal forward models that were acquired during motor training might not only be used for efficiently controlling fast motor behavior but also to facilitate extrapolation performance in purely perceptual tasks. In this study, we investigated whether preceding virtual cart-pole balancing training facilitates the ability to extrapolate the pole motion. We compared a group of 10 subjects, proficient in performing the cart-pole balancing task, to 10 naïve subjects. Our results demonstrate that preceding motor training increases the precision of pole movement extrapolation, although extrapolation is not trained explicitly. Additionally, we modelled subjects' behaviors and show that the difference in extrapolation performance can be explained by individual differences in the accuracy of internal forward models. When subjects are provided with feedback about the true pole movement in a second phase, both groups improve rapidly. The results indicate that the perceptual capability to extrapolate the state of the cartpole system accurately is implicitly trained during motor learning. We discuss these results in the context of shared representations and action-perception transfer.