Objective: The Ontario Neurodegeneration Research Initiative Program (1) is investigating patients with neurodegeneration (Alzheimer’s disease: AD; mild cognitive impairment: MCI; Parkinson’s disease: PD; amyotrophic lateral sclerosis: ALS; frontotemporal dementia: FTD; vascular cognitive impairment: VCI). The goal is to characterize predictors of neurodegeneration by cross referencing eye tracking metrics with detailed demographic, medical and neuropsychological assessment, genetics, quantitative MRI imaging, ocular and gait assessment.

Background: A method that is increasingly used in clinical investigations to assess sensory, motor, cognitive, and autonomic function is video-based eye tracking and pupillometry. Neurophysiological experiments have demonstrated that saccades and pupil size are controlled by converging inputs from both bottom-up sensory and top-down cognitive signals, and the circuits for saccade and pupil control are linked. Here, we examined saccade and pupil responses in AD, MCI, PD, ALS, FTD, and VCI and hypothesized that unique abnormal responses will be produced due to the different patterns of neurodegeneration.

Methods: We used high-speed (500Hz) video-based eye tracking of patients (n=469) and control (n=125) participants (ages 40-88 years). Participants were seated in front of a computer screen and performed 2 blocks of randomly interleaved pro- and anti-saccade trials (120 trials/block).  A coloured fixation point appeared at the centre of the screen to convey the instruction for a pro-saccade (look toward peripheral target) or anti-saccade (look away from peripheral target). We analyzed task errors, reaction times, accuracy, and metrics of the saccades and pupil responses.

Results: Patient had age-controlled abnormality on subsets of the dependent measures. Patients had altered saccadic reaction times, error rates, and pupil responses, compared to age-matched controls. However, the patterns of abnormality differed across the different diseases. Correlations between pupil measurements and saccadic reaction time were also altered in the patient groups.

Conclusions: We identified clear changes in saccade and pupil responses linked with neurodegeneration, identifying potential behavioural biomarkers for disease diagnosis and tracking disease progression. Combining the eye tracking with clinical and neuropsychological assessment, genetics, and brain imaging will validate these behavioural biomarkers.

References: 1) Farhan SM, Bartha R, Black SE, Corbett D, Finger E, Freedman M, Greenberg B, Grimes DA, Hegele RA, Hudson C, Kleinstiver PW, Lang AE, Masellis M, McIlroy WE, McLaughlin PM, Montero-Odasso M, Munoz DG, Munoz DP, Strother S, Swartz RH, Symons S, Tartaglia MC, Zinman L, ONDRI Investigators, Strong MJ (2016) The Ontario Neurodegenerative Disease Research Initiative (ONDRI). Can J Neurol Sci Dec 22:1-7. doi: 10.1017/cjn.2016.415. [Epub ahead of print].

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MDS Abstracts - https://www.mdsabstracts.org/abstract/using-eye-tracking-to-identify-pupil-and-saccade-biomarkers-of-neurodegenerative-disease/