Test–Retest Reliability of Saccadic Measures in Subjects at Risk for Huntington Disease

Blekher, Tanya; Weaver, Marjorie; Cai, Xueya; Hui, Siu L.; Marshall, Jessica; Jackson, Jacqueline; Wojcieszek, Joanne; Yee, Robert D.; Foroud, Tatiana

doi:10.1167/iovs.09-3538

Cited by 30 publications

(26 citation statements)

References 30 publications

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“…Study participants were recruited primarily from individuals who had taken part in previous HD research studies at Indiana University [4, 10, 21]. The study was approved by the institutional review board at Indiana University, and all participants gave informed consent prior to their inclusion in the study.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2011

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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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Section: Methodsmentioning

confidence: 99%

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

et al. 2011

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“…Saccades are typically slow and hypometric, and the more 'voluntary' types of saccade, such as anti-saccades and memory guided saccades, are particularly affected [5,6,24,25]. Saccadic reaction times or latency may be affected, though previously we have shown that it is more useful to look not just at mean latencies, but at their distributions, abnormalities of which can provide important quantitative neurological information that can be related to our knowledge of the underlying neural mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Huntington’s disease: changes in saccades and hand-tapping over 3 years

Antoniades

Mason

et al. 2010

J Neurol

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Saccades and hand-tapping are both potential biomarkers in patients with Huntington's disease (HD). While it is well known that patients with manifest Huntington's disease display abnormalities in both of these tasks, less is known about how these abnormalities progress over time, or to what extent premanifest patients are affected. This study was designed to address these issues. We examined premanifest and manifest Huntington's cohorts, together with a group of controls, over a 3-year period. Data were collected using a portable head-mounted saccadometer and a computerised hand-tapping device. Both premanifest and manifest Huntington's disease patients display significant and systematic changes from year to year in the parameters describing saccadic latency, while controls remain unchanged. By contrast, although hand-tapping was abnormal in HD patients, annual changes were much smaller. Measuring the rate of progression of saccadic abnormalities in manifest HD patients may provide a way to track disease progression, and thus help to evaluate novel therapies to modify the disease. The clear-cut progression in saccadic abnormalities in the premanifest group may prove useful in the future as a predictor of time to disease onset.

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“…Also, increased saccadic latencies (Blekher et al, 2006;Golding et al, 2006;Robert et al, 2009) and errors in saccadic direction have been reported in presymptomatic stages (Blekher et al, 2006). These results suggest that measures of saccadic movements are a possible indicator of disease stage in HD (Blekher et al, 2009). However, whether oculomotor performance parameters can be used to classify individuals according to their disease stage remains to be seen.…”

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confidence: 66%

“…Nonetheless, the replicability of measures within short time spans is important. The study by Blekher et al (2009) has shown that saccade latency and the percentage of errors have moderate to high replicability in control and premanifest HD groups (see also Klein & Fischer, 2005), whereas gain and velocity only present moderate reliability. Moreover, the replicability of the latter did not reach significance in a simple visually guided (prosaccade) task.…”

Section: Discussionmentioning

confidence: 98%

Classification of Huntington’s disease stage with support vector machines: A study on oculomotor performance

et al. 2015

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Alterations in oculomotor performance are among the first observable physical alterations during presymptomatic stages of Huntington's disease (HD). Quantifiable measurements of oculomotor performance have been studied as possible markers of disease status and progression in presymptomatic and early symptomatic stages of HD, on the basis of traditional analysis methods. Whether oculomotor performance can be used to classify individuals according to HD disease stage has yet to be explored via the application of machine-learning methods. In the present study, we report the application of the support vector machine (SVM) algorithm to oculomotor features pooled from a four-task psychophysical experiment. We were able to automatically distinguish control participants from presymptomatic HD (pre-HD) participants with an accuracy of 73.47 %, a sensitivity of 74.31 %, and a specificity of 72.64 %; to distinguish control participants from HD patients with an accuracy of 81.84 %, a sensitivity of 76.19 %, and a specificity of 87.48 %; and to distinguish pre-HD participants from HD patients with an accuracy of 83.54 %, a sensitivity of 92.62 %, and a specificity of 74.45 %. These results demonstrate that the application of supervised classification methods to oculomotor features is a valuable and promising approach to the automatic detection of disease stage in HD.

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Test–Retest Reliability of Saccadic Measures in Subjects at Risk for Huntington Disease

Abstract: Good reliability of saccadic latency and percentage of errors in both antisaccade and memory-guided tasks suggests that these measures could serve as biomarkers to evaluate progression in HD.

Cited by 30 publications

References 30 publications

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

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

Huntington’s disease: changes in saccades and hand-tapping over 3 years

Classification of Huntington’s disease stage with support vector machines: A study on oculomotor performance

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