Abstract

Background: In Huntington’s disease there is evidence of structural damage in the motor system, but it is still unclear how to link this to the behavioral disorder of movement. One feature of choreic movement is variable timing and coordination between sequences of actions. We postulate this results from desynchronization of neural activity in cortical motor areas. Objectives: The objective of this study was to explore the ability to synchronize activity in a motor network using transcranial magnetic stimulation and to relate this to timing of motor performance. Methods: We examined synchronization in oscillatory activity of cortical motor areas in response to an external input produced by a pulse of transcranial magnetic stimulation. We combined this with EEG to compare the response of 16 presymptomatic Huntington’s disease participants with 16 age-matched healthy volunteers to test whether the strength of synchronization relates to the variability of motor performance at the following 2 tasks: a grip force task and a speeded-tapping task. Results: Phase synchronization in response to M1 stimulation was lower in Huntington’s disease than healthy volunteers (P<.01), resulting in a reduced cortical activity at global (P<.02) and local levels (P<.01). Participants who showed better timed motor performance also showed stronger oscillatory synchronization (r 5 20.356; P<.05) and higher cortical activity (r 5 20.393; P<.05). Conclusions: Our data may model the ability of the motor command to respond to more subtle, physiological inputs from other brain areas. This novel insight indicates that impairments of the timing accuracy of synchronization and desynchronization could be a physiological basis for some key clinical features of Huntington’s disease.

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