Neural modeling of antisaccade performance of healthy controls and early Huntington's disease patients

Abstract

Huntington's disease (HD), a genetically determined neurodegenerative disease, is positively correlated with eye movement abnormalities in decision making. The antisaccade conflict paradigm has been widely used to study response inhibition in eye movements and reliable performance deficits in HD subjects have been observed including greater number and timing of direction errors. We recorded the error rates and response latencies of early HD patients and healthy age-matched controls performing the mirror antisaccade task. HD participants displayed slower and more variable antisaccade latencies and increased error rates relative to healthy controls. A competitive accumulator-to-threshold neural model was then employed to quantitatively simulate the controls' and patients' reaction latencies and error rates and uncover the mechanisms giving rise to the observed HD antisaccade deficits. Our simulations showed: 1) a more gradual and noisy rate of accumulation of evidence by HD patients is responsible for the observed prolonged and more variable antisaccade latencies in early HD; 2) the confidence level of early HD patients making a decision is unaffected by the disease; and 3) the antisaccade performance of healthy controls and early HD patients is the end product of a neural lateral competition (inhibition) between a correct and an erroneous decision process, and not the end product of a third top-down stop signal suppressing the erroneous decision process as many have speculated.

Reflexive and voluntary saccadic eye movements as biomarker of Huntington’s Disease

“…This data is in contrast with those of other studies. Prolonged latency and increased latency variability of volitional saccades in presymptomatic carriers was previously noted [12][13][14]. Similar results were obtained by Golding et al, who showed prolonged latency of memory-guided saccades and increased variability of saccades latency [10].…”

“…Saccade disorders are present at an early stage of HD among relatives of patients, and herald the imminent development of the disease [4]. Saccade deficits have been well documented in premanifest and manifest HD patients, and are considered potential biomarkers of disease development and progression [5][6][7][8][9][10][11][12][13][14][15][16][17]. The structural abnormalities of the optic nerve and retina displayed in pre-symptomatic HD carriers could be other potential biomarkers that would be of great interest in HD gene therapies [18].…”

Minimal reporting guideline for research involving eye tracking (2023 edition)

“…Next, to remove remaining blinkrelated artefacts, all data ≤ 75 ms either side of all gaps in the data were also deleted. Position data were then filtered using a generalized Savitzky-Golay filter […] Saccades were detected using the method described by Engbert and Kliegl" (Cutsuridis et al, 2021).…”