Eye tracking identifies biomarkers in α-synucleinopathies versus progressive supranuclear palsy

Abstract

Objectives This study (1) describes and compares saccade and pupil abnormalities in patients with manifest alpha-synucleinopathies (αSYN: Parkinson’s disease (PD), Multiple System Atrophy (MSA)) and a tauopathy (progressive supranuclear palsy (PSP)); (2) determines whether patients with rapid-eye-movement sleep behaviour disorder (RBD), a prodromal stage of αSYN, already have abnormal responses that may indicate a risk for developing PD or MSA. Methods Ninety (46 RBD, 27 PD, 17 MSA) patients with an αSYN, 10 PSP patients, and 132 healthy age-matched controls (CTRL) were examined with a 10-min video-based eye-tracking task (Free Viewing). Participants were free to look anywhere on the screen while saccade and pupil behaviours were measured. Results PD, MSA, and PSP spent more time fixating the centre of the screen than CTRL. All patient groups made fewer macro-saccades (> 2◦ amplitude) with smaller amplitude than CTRL. Saccade frequency was greater in RBD than in other patients. Following clip change, saccades were temporarily suppressed, then rebounded at a slower pace than CTRL in all patient groups. RBD had distinct, although discrete saccade abnormalities that were more marked in PD, MSA, and even more in PSP. The vertical saccade rate was reduced in all patients and decreased most in PSP. Clip changes produced large increases or decreases in screen luminance requiring pupil constriction or dilation, respectively. PSP elicited smaller pupil constriction/dilation responses than CTRL, while MSA elicited the opposite. Conclusion RBD patients already have discrete but less pronounced saccade abnormalities than PD and MSA patients. Vertical gaze palsy and altered pupil control differentiate PSP from αSYN.

Emotion Recognition in Multiple System Atrophy: An Exploratory Eye-Tracking Study

“…In addition, we found fewer overall fixations and a center bias in MSA patients compared to PD patients and HCs. This is in line with a recent study on patients with PD, MSA and progressive supranuclear palsy that showed a reduction in macro saccades and a strong center bias in these patients compared to HCs [ 44 ]. Although the reason for this center bias remains unclear, it is possible that increased anxiety as well as higher alexithymia scores may be responsible for this gaze pattern in our MSA cohort.…”

Reflexive and volitional saccadic eye movements and their changes in age and progressive supranuclear palsy

“…Slow and small saccades, predominantly in the vertical direction, are a defining clinical feature of PSP [14], caused by degeneration in brainstem areas that control eye movements [15,16]. Degeneration in PSP also occurs in brain regions concerned with high-level control of eye movements, such as the basal ganglia [17], resulting in wide-ranging, sometimes contradictory, effects on various eye movements [18][19][20][21]. A more comprehensive mapping of saccadic parameters in PSP will aid our understanding of disease pathology to improve diagnosis, which remains a significant unmet clinical challenge in the early stages of the disease [22][23][24].…”

Attentional Modulation of Eye Blinking Is Altered by Sex, Age, and Task Structure

“…So far, our lab has used the tasks described in this paper to differentiate saccade and pupil dynamics in multiple neurodegenerative and psychiatric cohorts ( Wang et al, 2016 ; Perkins et al, 2021 ; Habibi et al, 2022 ; Riek et al, 2023 ), making blinks an obvious next candidate for use in detecting clinically relevant deficits in cognitive pathways, especially given the findings described here. Alterations in blink behavior have already been observed in many neurological conditions ( Karson et al, 1984 ; Basso et al, 1996 ) but would benefit from the more temporally sensitive, probabilistic approaches to blink analysis implemented in this study to expose the higher-level mechanisms underlying the behavior ( Brien et al, 2023 ; Calancie et al, 2023 ).…”