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I13 Variability In Interval Production Is Due To Timing Dependent Deficits In Early Huntington’s Disease
  1. AK Rao1,
  2. J Uddin2,
  3. K Marder3,
  4. BC Rakitin3
  1. 1Department of Rehabilitation Medicine (Physical Therapy), and G. H. Sergievsky Center, Columbia University, New York, NY, USA
  2. 2Department of Rehabilitation Medicine (Physical Therapy), Columbia University, New York, NY, USA
  3. 3G. H. Sergievsky Center,Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, and Departments of Neurology and Psychiatry, Columbia University, New York, NY, USA

Abstract

Background In Huntington’s disease (HD) increased variability is seen in performance of motor tasks that require implicit control of timing. We examined if timing variability was also evident in an explicit interval-timing task.

Methods Sixty subjects (21 controls, 19 manifest HD and 20 pre-manifest HD) performed a single interval production task with three target intervals (1.1s, 2.2s, 3.3s). We analysed accuracy (proportional error) and precision (standard deviation) across groups and intervals.

Results No differences were seen in accuracy across groups or intervals. Precision was significantly lower in manifest (p = 0.0001) and pre-manifest HD (p = 0.04) compared with controls. This was particularly true for pre-manifest subjects close to diagnosis (based on probability of diagnosis in five years). Precision was correlated with proximity to diagnosis (r2=0.3, p < 0.01). To examine the source of reduced precision, we conducted linear regression of standard deviation with interval duration. Slope of the regression was significantly higher in manifest HD (p = 0.02) and in pre-manifest HD close to diagnosis (p = 0.04) compared with controls and pre-manifest participants far from diagnosis.

Conclusions Timing precision is impaired before clinical diagnosis in Huntington’s disease. Slope analysis suggests that timing variability (decreased precision) was due to deficits in timing dependent processes. Our results provide additional support for the proposal that the basal ganglia are implicated in central timekeeping functions. Since the single interval production task was sensitive to deficits in pre-manifest HD, temporal precision may be a useful outcome measure in future clinical trials.

KeyWords
  • Huntington’s disease; pre-manifest
  • timing
  • interval production
  • variability

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