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Comparison of vertical and horizontal saccade measures and their relation to gray matter changes in premanifest and manifest Huntington disease

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Abstract

Saccades are a potentially important biomarker of Huntington disease (HD) progression, as saccadic abnormalities can be detected both cross-sectionally and longitudinally. Although vertical saccadic impairment was reported decades ago, recent studies have focused on horizontal saccades. This study investigated antisaccade (AS) and memory guided saccade (MG) impairment in both the horizontal and vertical directions in individuals with the disease-causing CAG expansion (CAG+; n = 74), using those without the expansion (CAG−; n = 47) as controls. Percentage of errors, latency, and variability of latency were used to measure saccadic performance. We evaluated the benefits of measuring saccades in both directions by comparing effect sizes of horizontal and vertical measures, and by investigating the correlation of saccadic measures with underlying gray matter loss. Consistent with previous studies, AS and MG impairments were detected prior to the onset of manifest disease. Furthermore, the largest effect sizes were found for vertical saccades. A subset of participants (12 CAG−, 12 premanifest CAG+, 7 manifest HD) underwent magnetic resonance imaging, and an automated parcellation and segmentation procedure was used to extract thickness and volume measures in saccade-generating and inhibiting regions. These measures were then tested for associations with saccadic impairment. Latency of vertical AS was significantly associated with atrophy in the left superior frontal gyrus, left inferior parietal lobule, and bilateral caudate nuclei. This study suggests an important role for measuring vertical saccades. Vertical saccades may possess more statistical power than horizontal saccades, and the latency of vertical AS is associated with gray matter loss in both cortical and subcortical regions important in saccade function.

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Acknowledgments

We gratefully acknowledge the individuals who participated in this study. We also thank Xabier Beristain, Jeanine Marshall, Marjorie Weaver, Michele Beal, Veronique Bragulat, and Courtney Robbins who provided expertise and technical support for the study. This work was supported by National Institute of Health Grants R01NS042659, R21NS060205, N01NS-3-2357, M01RR-00750, UL1RR025761, P30AG10133-18S1, a pilot Grant from the Center for Neuroimaging at Indiana University School of Medicine, a Research Support Fund Grant from Indiana University-Purdue University Indianapolis, and support from the CHDI Foundation, project 1214.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Medical and Molecular Genetics, Indiana University School of Medicine, 410 W. 10th Street (HS 4021), Indianapolis, IN, 46202-5251, USA

    Jason Rupp & Tatiana Foroud

  2. Department of Neurology, Indiana University School of Medicine, 541 Clinical Drive (CL 285), Indianapolis, IN, 46202, USA

    Mario Dzemidzic & David A. Kareken

  3. Division of Imaging Sciences, Department of Radiology and Imaging Science, Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, USA

    Mario Dzemidzic, John West, Andrew J. Saykin & David A. Kareken

  4. Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN, USA

    Tanya Blekher

  5. Division of Biostatistics, Department of Medicine, Regenstrief Institute, Indiana University School of Medicine, Indianapolis, IN, USA

    Siu Hui

  6. Department of Neurology, Indiana University School of Medicine, 545 Barnhill Drive (EH 125), Indianapolis, IN, 46202, USA

    Joanne Wojcieszek

  7. Department of Medical and Molecular Genetics, Indiana University School of Medicine, 950 Walnut Street (R2 E124), Indianapolis, IN, 46202, USA

    Andrew J. Saykin

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  1. Jason Rupp
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Correspondence to David A. Kareken or Tatiana Foroud.

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Rupp, J., Dzemidzic, M., Blekher, T. et al. Comparison of vertical and horizontal saccade measures and their relation to gray matter changes in premanifest and manifest Huntington disease. J Neurol 259, 267–276 (2012). https://doi.org/10.1007/s00415-011-6172-0

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