Response to sensory uncertainty in Parkinson’s disease: a marker of cerebellar dysfunction?

Authors

  • James K. R. Stevenson,

    1. Department of Neuroscience, University of British Columbia, Vancouver, BC, Canada
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  • Meeko M. K. Oishi,

    1. Department of Electrical and Computer Engineering, University of British Columbia, Vancouver, BC, Canada
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  • Sara Farajian,

    1. Department of Electrical and Computer Engineering, University of British Columbia, Vancouver, BC, Canada
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  • Edmond Cretu,

    1. Department of Electrical and Computer Engineering, University of British Columbia, Vancouver, BC, Canada
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  • Edna Ty,

    1. Pacific Parkinson’s Research Centre, University of British Columbia, Purdy Pavilion, 2221 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada
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  • Martin J. McKeown

    1. Department of Neuroscience, University of British Columbia, Vancouver, BC, Canada
    2. Department of Electrical and Computer Engineering, University of British Columbia, Vancouver, BC, Canada
    3. Pacific Parkinson’s Research Centre, University of British Columbia, Purdy Pavilion, 2221 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada
    4. Department of Medicine (Neurology), University of British Columbia, Vancouver, BC, Canada
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Dr M. J. McKeown, 3Pacific Parkinson’s Research Centre, as above.
E-mail: mmckeown@interchange.ubc.ca

Abstract

Motor performance is profoundly influenced by sensory information, yet sensory input can be noisy and uncertain. The basal ganglia and the cerebellum are important in processing sensory uncertainty, as the basal ganglia incorporate the uncertainty of predictive reward cues to reinforce motor programs, and the cerebellum and its connections mitigate the effect of ambiguous sensory input on motor performance through the use of forward models. Although Parkinson’s disease (PD) is classically considered a primary disease of the basal ganglia, alterations in cerebellar activation are also observed, which may have consequences for the processing of sensory uncertainty. The aim of this study was to investigate the effect of visual uncertainty on motor performance in 15 PD patients and ten age-matched control subjects. Subjects performed a visually guided tracking task, requiring large-amplitude arm movements, by tracking with their index finger a moving target along a smooth trajectory. To induce visual uncertainty, the target position randomly jittered about the desired trajectory with increasing amplitudes. Tracking error was related to target ambiguity to a significantly greater degree in PD subjects off medication compared with control subjects, indicative of susceptibility to visual uncertainty in PD. l-Dopa partially ameliorated this deficit. We interpret our findings as suggesting an inability of PD subjects to create adequate forward models and/or de-weight less informative visual input. As these computations are normally associated with the cerebellum and connections, we suggest that alterations in normal cerebellar functioning may be a significant contributor to altered motor performance in PD.

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