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

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.

Consistent Neurodegeneration and Its Association with Clinical Progression in Huntington's Disease: A Coordinate-Based Meta-Analysis

“…We further found consistent atrophy in the inferior parietal cortex and intraparietal sulcus, playing an important role in higher cognitive functioning and somatosensory and visuomotor integration [50]. For instance, Rupp et al [51] reported significant associations between degeneration in the left inferior parietal lobule and antisaccade in HD, an important phenotypical feature in HD. Finally, volume reductions in the insula were associated with emotion processing deficits in HD, especially for the recognition of disgust, which is already detectable before symptom onset [52].…”

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

“…For example, quantitative measurements of eye movements such as saccade latency and duration, as well as errors in oculomotor tasks, have been studied as possible biomarkers of presymptomatic and early symptomatic stages of HD (Ali, Michell, Barker, & Carpenter, 2006;Blekher et al, 2006;Golding, Danchaivijitr, Hodgson, Tabrizi, & Kennard, 2006;Patel, Jankovic, Hood, Jeter, & Sereno, 2012). The results from clinical HD patients have consistently shown significantly increased saccadic latencies (Ali et al, 2006;Antoniades, Xu, Mason, Carpenter, & Barker, 2010;Avanzini, Girotti, Caraceni, & Spreafico, 1979;Blekher et al, 2006;Golding et al, 2006;Patel et al, 2012;Rupp et al, 2012), saccadic durations (Ali et al, 2006;Avanzini et al, 1979), and errors in saccadic direction (Blekher et al, 2006;Patel et al, 2012;Rupp et al, 2012). 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).…”

Huntington's Disease for Brain Mapping: An Encyclopedic Reference

“…Motor impairment, including psychomotor performance, is associated with striatal volume (and other basal ganglia) loss in HD patients (Jurgens et al, 2008;Ruocco, Bonilha, Li, Lopes-Cendes, & Cendes, 2008;Scahill et al, 2013;Van Den Bogaard et al, 2011) and premanifest gene carriers (Biglan et al, 2009;Vandenberghe et al, 2009) and extends to cortical areas for psychomotor and visual motor tasks (Bechtel et al, 2010;Jurgens et al, 2008;Rupp et al, 2012;Scahill et al, 2013). Poor performance during emotion recognition, executive function, memory, and olfactory tasks is also associated with a reduced volume in both the striatum (Henley et al, 2012) and cortex (Henley et al, 2012;Ille et al, 2011;Papp et al, 2013;Scahill et al, 2013).…”