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fMRI detection of early neural dysfunction in preclinical Huntington's disease

Published online by Cambridge University Press:  14 August 2007

JANICE L. ZIMBELMAN ,
JANE S. PAULSEN ,
ANIA MIKOS ,
NORMAN C. REYNOLDS ,
RAYMOND G. HOFFMANN  and
STEPHEN M. RAO
JANICE L. ZIMBELMAN
Affiliation:
Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin Schey Center for Cognitive Neuroimaging, Cleveland Clinic Foundation, Cleveland, Ohio
JANE S. PAULSEN
Affiliation:
Department of Psychiatry, University of Iowa College of Medicine, Iowa City, Iowa
ANIA MIKOS
Affiliation:
Department of Psychiatry, University of Iowa College of Medicine, Iowa City, Iowa
NORMAN C. REYNOLDS
Affiliation:
Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin
RAYMOND G. HOFFMANN
Affiliation:
Department of Biostatistics, Medical College of Wisconsin, Milwaukee, Wisconsin
STEPHEN M. RAO
Affiliation:
Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin Schey Center for Cognitive Neuroimaging, Cleveland Clinic Foundation, Cleveland, Ohio
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Abstract

Neuropsychological and neuroimaging changes have been observed in individuals with the Huntington's disease (HD) gene expansion prior to the onset of manifest HD. This cross-sectional fMRI study of preclinical HD (pre-HD) individuals was conducted to determine if functional brain changes precede deficits in behavioral performance and striatal atrophy. Twenty-six pre-HD and 13 demographically matched healthy participants performed a time reproduction task while undergoing fMRI scanning. Pre-HD participants were divided into two groups (n = 13 each): FAR (>12 years to estimated onset [YEO] of manifest HD) and CLOSE (<12 YEO). The CLOSE group demonstrated behavioral deficits, striatal atrophy, and reduced neural activation in the left putamen, SMA, left anterior insula and right inferior frontal gyrus. The FAR group showed reduced neural activation in the right anterior cingulate and right anterior insula. The FAR group also demonstrated increased neural activation in the left sensorimotor, left medial frontal gyrus, left precentral gyrus, bilateral superior temporal gyri and right cerebellum. The fMRI changes in the FAR group occurred in the relative absence of striatal atrophy and behavioral performance deficits. These results suggest that fMRI is sensitive to neural dysfunction occurring more than 12 years prior to the estimated onset of manifest HD. (JINS, 2007, 13, 758–769.)

Keywords

Magnetic resonance imagingBasal gangliaTime reproductionEarly detection
Type
Research Article
Information
Journal of the International Neuropsychological Society , Volume 13 , Issue 5 , September 2007 , pp. 758 - 769
Copyright
2007 The International Neuropsychological Society

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