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Motor disorder in Huntington's disease begins as a dysfunction in error feedback control

Nature volume 403, pages 544–549 (2000)Cite this article

Abstract

A steady progression of motor dysfunction takes place in Huntington's disease1 (HD). The origin of this disturbance with relation to the motor control process is not understood. Here we studied reaching movements in asymptomatic HD gene-carriers (AGCs) and subjects with manifest HD. We found that movement jerkiness, which characterizes the smoothness and efficiency of motion, was a sensitive indicator of presymptomatic HD progression. A large fraction of AGCs displayed elevated jerk even when more than seven years remained until predicted disease onset. Movement termination was disturbed much more than initiation and was highly variable from trial to trial. Analysis of this variability revealed that the sensitivity of end-movement jerk to subtle, self-generated early-movement errors was greater in HD subjects than in controls. Additionally, we found that HD corrective responses to externally-generated force pulses were greatly disturbed, indicating that HD subjects display aberrant responses to both external and self-generated errors. Because feedback corrections are driven by error and are delayed such that they predominantly affect movement termination, these findings suggest that a dysfunction in error correction characterizes the motor control deficit in early HD. This dysfunction may be observed years before clinical disease onset and grows worse as the disease progresses.

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Figure 1: Hand paths from selected subjects after 200 practice trials (movements 201–300).
Figure 2: Quantification of movement properties.
Figure 3: Squared jerk profiles for different movement speeds.
Figure 4: Errors that occur early in the movement, before the hand reaches its peak speed, predict jerk that occurs later.
Figure 5: Force-pulse perturbations disturb the movements of HD subjects more than controls or cerebellar subjects.

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Acknowledgements

We thank K. Thoroughman and N. Bhushan. R.S. and M.S. conceived of the experiments, M.S. collected the data, and designed and carried out the data analysis guided by interaction with R.S., J.B., N.B. and K.T. M.S. and R.S. wrote the manuscript. The Johns Hopkins HD Center (director C. A. Ross) arranged patient visits and clinical assessment of HD patients. The work was supported by grants from the Whitaker Foundation (R.S.) and the National Institutes of Health (R.S. and J.B.), and a pre-doctoral fellowship from the National Institute of General Medical Sciences to M.S.

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Authors and Affiliations

  1. Department of Biomedical Engineering,

    Maurice A. Smith & Reza Shadmehr

  2. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, 21205-2195, Maryland , USA

    Jason Brandt

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  1. Maurice A. Smith
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  2. Jason Brandt
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Correspondence to Maurice A. Smith.

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Smith, M., Brandt, J. & Shadmehr, R. Motor disorder in Huntington's disease begins as a dysfunction in error feedback control. Nature 403, 544–549 (2000). https://doi.org/10.1038/35000576

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