RESUMEN
Oculomotor tasks generate a potential wealth of behavioural biomarkers for neurodegenerative diseases. Overlap between oculomotor and disease-impaired circuitry reveals the location and severity of disease processes via saccade parameters measured from eye movement tasks such as prosaccade and antisaccade. Existing studies typically examine few saccade parameters in single diseases, using multiple separate neuropsychological test scores to relate oculomotor behaviour to cognition; however, this approach produces inconsistent, ungeneralizable results and fails to consider the cognitive heterogeneity of these diseases. Comprehensive cognitive assessment and direct inter-disease comparison are crucial to accurately reveal potential saccade biomarkers. We remediate these issues by characterizing 12 behavioural parameters, selected to robustly describe saccade behaviour, derived from an interleaved prosaccade and antisaccade task in a large cross-sectional data set comprising five disease cohorts (Alzheimer's disease/mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson's disease, and cerebrovascular disease; n = 391, age 40-87) and healthy controls (n = 149, age 42-87). These participants additionally completed an extensive neuropsychological test battery. We further subdivided each cohort by diagnostic subgroup (for Alzheimer's disease/mild cognitive impairment and frontotemporal dementia) or degree of cognitive impairment based on neuropsychological testing (all other cohorts). We sought to understand links between oculomotor parameters, their relationships to robust cognitive measures, and their alterations in disease. We performed a factor analysis evaluating interrelationships among the 12 oculomotor parameters and examined correlations of the four resultant factors to five neuropsychology-based cognitive domain scores. We then compared behaviour between the abovementioned disease subgroups and controls at the individual parameter level. We theorized that each underlying factor measured the integrity of a distinct task-relevant brain process. Notably, Factor 3 (voluntary saccade generation) and Factor 1 (task disengagements) significantly correlated with attention/working memory and executive function scores. Factor 3 also correlated with memory and visuospatial function scores. Factor 2 (pre-emptive global inhibition) correlated only with attention/working memory scores, and Factor 4 (saccade metrics) correlated with no cognitive domain scores. Impairment on several mostly antisaccade-related individual parameters scaled with cognitive impairment across disease cohorts, while few subgroups differed from controls on prosaccade parameters. The interleaved prosaccade and antisaccade task detects cognitive impairment, and subsets of parameters likely index disparate underlying processes related to different cognitive domains. This suggests that the task represents a sensitive paradigm that can simultaneously evaluate a variety of clinically relevant cognitive constructs in neurodegenerative and cerebrovascular diseases and could be developed into a screening tool applicable to multiple diagnoses.
RESUMEN
The capacity for inhibitory control is an important cognitive process that undergoes dynamic changes over the course of the lifespan. Robust characterization of this trajectory, considering age continuously and using flexible modeling techniques, is critical to advance our understanding of the neural mechanisms that differ in healthy aging and neurological disease. The interleaved pro/anti-saccade task (IPAST), in which pro- and anti-saccade trials are randomly interleaved within a block, provides a simple and sensitive means of assessing the neural circuitry underlying inhibitory control. We utilized IPAST data collected from a large cross-sectional cohort of normative participants (n = 604, 5-93 years of age), standardized pre-processing protocols, generalized additive modeling, and change point analysis to investigate the effect of age on saccade behavior and identify significant periods of change throughout the lifespan. Maturation of IPAST measures occurred throughout adolescence, while subsequent decline began as early as the mid-20s and continued into old age. Considering pro-saccade correct responses and anti-saccade direction errors made at express (short) and regular (long) latencies was crucial in differentiating developmental and aging processes. We additionally characterized the effect of age on voluntary override time, a novel measure describing the time at which voluntary processes begin to overcome automated processes on anti-saccade trials. Drawing on converging animal neurophysiology, human neuroimaging, and computational modeling literature, we propose potential frontal-parietal and frontal-striatal mechanisms that may mediate the behavioral changes revealed in our analysis. We liken the models presented here to "cognitive growth curves" which have important implications for improved detection of neurological disease states that emerge during vulnerable windows of developing and aging.
RESUMEN
BACKGROUND: Parkinson's disease (PD) patients exhibit deficits in saccade performance, pupil function, and blink rate. Isolated REM (rapid eye movement) Sleep Behavior Disorder (RBD) is a harbinger to PD making them candidates to investigate for early oculomotor abnormalities as PD biomarkers. OBJECTIVES: We tested whether saccade, pupillary, and blink responses in RBD were similar to PD. METHODS: RBD (n = 22), PD (n = 22) patients, and healthy controls (CTRL) (n = 74) were studied with video-based eye-tracking. RESULTS: RBD patients did not have significantly different saccadic behavior compared to CTRL, but PD patients differed from CTRL and RBD. Both patient groups had significantly lower blink rates, dampened pupil constriction, and dilation responses compared to CTRL. CONCLUSION: RBD and PD patients had altered pupil and blink behavior compared to CTRL. Because RBD saccade parameters were comparable to CTRL, pupil and blink brain areas may be impacted before saccadic control areas, making them potential prodromal PD biomarkers. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
