Smith MA, Brandt J, Shadmehr R (2000) Motor disorders in
Huntington's disease begins as a dysfunction in error feedback control. Nature,
403:544-549.
Abstract:
A steady
progression of motor dysfunction takes place in Huntington's disease (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 7 years remained until predicted disease
onset. Movement termination was disturbed much more than initiation yet 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 dramatically
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 effect 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 it worsens with disease progression.
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