Hostname: page-component-848d4c4894-hfldf Total loading time: 0 Render date: 2024-05-01T04:31:56.063Z Has data issue: false hasContentIssue false

Motor timing variability increases in preclinical Huntington's disease patients as estimated onset of motor symptoms approaches

Published online by Cambridge University Press:  20 March 2007

SEAN C. HINTON
Affiliation:
Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin
JANE S. PAULSEN
Affiliation:
Departments of Psychiatry and Neurology, University of Iowa, Iowa City, Iowa
RAYMOND G. HOFFMANN
Affiliation:
Division of Biostatistics, Medical College of Wisconsin, Milwaukee, Wisconsin
NORMAN C. REYNOLDS
Affiliation:
Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin
JANICE L. ZIMBELMAN
Affiliation:
Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin
STEPHEN M. RAO
Affiliation:
Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin

Abstract

Huntington's disease (HD) is a neurodegenerative disorder diagnosed clinically with the development of choreiform movements. However, neuropsychological studies have demonstrated cognitive and psychiatric changes during the preclinical phase (pre-HD) prior to formal diagnosis. Previous studies have demonstrated the sensitivity of time reproduction tasks to basal ganglia pathology, as seen in clinical HD and Parkinson's disease. In this study, 29 pre-HD participants, ranging from 3 to 39 years from estimated onset (YEO) of HD based on genetic testing and chronological age, were administered the paced finger-tapping task using target intervals of 600 and 1200 ms. Mean inter-response interval, a measure of timing accuracy, did not systematically deviate from the target interval as a function of YEO. In contrast, timing variability increased curvilinearly as a function of YEO, but not with chronological age alone. Motor timing variability, but not accuracy, may serve as a marker to define the earliest behavioral changes in HD. The present study is among the first to examine the relationship between behavioral measures and YEO in pre-HD. (JINS, 2007, 13, 539–543.)

Type
BRIEF COMMUNICATION
Copyright
© 2007 The International Neuropsychological Society

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Aylward, E.H., Codori, A.M., Rosenblatt, A., Sherr, M., Brandt, J., Stine, O.C., Barta, P.E., Pearlson, G.D., & Ross, C.A. (2000). Rate of caudate atrophy in presymptomatic and symptomatic stages of Huntington's disease. Movement Disorders, 15, 552560.Google Scholar
Aylward, E.H., Reiss, A.L., Reader, M.J., Singer, H.S., Brown, J.E., & Denckla, M.B. (1996). Basal ganglia volumes in children with attention-deficit hyperactivity disorder. Journal of Child Neurology, 11, 112115.Google Scholar
Aylward, E.H., Sparks, B.F., Field, K.M., Yallapragada, V., Shpritz, B.D., Rosenblatt, A., Brandt, J., Gourley, L.M., Liang, K., Zhou, H., Margolis, R.L., & Ross, C.A. (2004). Onset and rate of striatal atrophy in preclinical Huntington disease. Neurology, 63, 6672.Google Scholar
Campodonico, J.R., Aylward, E., Codori, A.M., Young, C., Krafft, L., Magdalinski, M., Ranen, N., Slavney, P.R., & Brandt, J. (1998). When does Huntington's disease begin? Journal of the International Neuropsychological Society, 4, 467473.Google Scholar
Elsinger, C.L., Rao, S.M., Zimbelman, J.L., Reynolds, N.C., Blindauer, K.A., & Hoffmann, R.G. (2003). Neural basis for impaired time reproduction in Parkinson's disease: An fMRI study. Journal of the International Neuropsychological Society, 9, 10881098.Google Scholar
Harrington, D.L. & Haaland, K.Y. (1999). Neural underpinnings of temporal processing: A review of focal lesion, pharmacological, and functional imaging research. Reviews in the Neurosciences, 10, 91116.Google Scholar
Harrington, D.L., Haaland, K.Y., & Hermanowicz, N. (1998). Temporal processing in the basal ganglia. Neuropsychology, 12, 312.Google Scholar
Hersch, S.M. & Rosas, H.D. (2001). Neuroprotective therapy for Huntington's disease: New prospects and challenges. Expert Review of Neurotherapeutics, 1, 111118.Google Scholar
Huntington Study Group (1996). Unified Huntington's Disease Rating Scale: Reliability and consistency. Movement Disorders, 11, 136142.Google Scholar
Langbehn, D.R., Brinkman, R.R., Falush, D., Paulsen, J.S., Hayden, M.R., & International Huntington's Disease Collaborative Group. (2004). A new model for prediction of the age of onset and penetrance for Huntington's disease based on CAG length. Clinical Genetics, 65, 267277.Google Scholar
Paulsen, J.S., Hayden, M., Stout, J.C., Langbehn, D.R., Aylward, E., Ross, C.A., Guttman, M., Nance, M., Kieburtz, K., Oakes, D., Shoulson, I., Kayson, E., Johnson, S., Penziner, E., & the Predict-HD Investigators of the Huntington Study Group (2006). Preparing for preventive clinical trials: The Predict-HD study. Archives of Neurology, 63, 883890.Google Scholar
Paulsen, J.S., Zhao, H., Stout, J.C., Brinkman, R.R., Guttman, M., Ross, C.A., Como, P., Manning, C., Hayden, M.R., & Shoulson, I. (2001). Clinical markers of early disease in persons near onset of Huntington's disease. Neurology, 57, 658662.Google Scholar
Paulsen, J.S., Zimbelman, J.L., Hinton, S.C., Langbehn, D.R., Leveroni, C.L., Benjamin, M.L., Reynolds, N.C., & Rao, S.M. (2004). fMRI biomarker of early neuronal dysfunction in presymptomatic Huntington's disease. American Journal of Neuroradiology, 25, 17151721.Google Scholar
Rao, S.M., Harrington, D.L., Haaland, K.Y., Bobholz, J.A., Cox, R.W., & Binder, J.R. (1997). Distributed neural systems underlying the timing of movements. Journal of Neuroscience, 17, 55285535.Google Scholar
Rao, S.M., Mayer, A.R., & Harrington, D.L. (2001). The evolution of brain activation during temporal processing. Nature Neuroscience, 4, 317323.Google Scholar
Woodruff-Pak, D.S. & Papka, M. (1996). Huntington's disease and eyeblink classical conditioning: Normal learning but abnormal timing. Journal of the International Neuropsychological Society, 2, 323334.Google Scholar