Riek Heidi C, Brien Donald C, Coe Brian C, Huang Jeff, Perkins Julia E, Yep Rachel, McLaughlin Paula M, Orange Joseph B, Peltsch Alicia J, Roberts Angela C, Binns Malcolm A, Lou Wendy, Abrahao Agessandro, Arnott Stephen R, Beaton Derek, Black Sandra E, Dowlatshahi Dar, Finger Elizabeth, Fischer Corinne E, Frank Andrew R, Grimes David A, Kumar Sanjeev, Lang Anthony E, Lawrence-Dewar Jane M, Mandzia Jennifer L, Marras Connie, Masellis Mario, Pasternak Stephen H, Pollock Bruce G, Rajji Tarek K, Sahlas Demetrios J, Saposnik Gustavo, Seitz Dallas P, Shoesmith Christen, Steeves Thomas D L, Strother Stephen C, Sunderland Kelly M, Swartz Richard H, Tan Brian, Tang-Wai David F, Tartaglia Maria Carmela, Turnbull John, Zinman Lorne, Munoz Douglas P
Centre for Neuroscience Studies, Queen's University, Kingston, Ontario K7L 3N6Canada.
Nova Scotia Health, Halifax, Nova Scotia B3S 0H6, Canada.
Brain Commun. 2023 Mar 2;5(2):fcad049. doi: 10.1093/braincomms/fcad049. eCollection 2023.
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; = 391, age 40-87) and healthy controls ( = 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.
眼球运动任务可为神经退行性疾病生成大量潜在的行为生物标志物。眼球运动与疾病受损神经回路之间的重叠，通过从前瞻性扫视和反扫视等眼动任务中测量的扫视参数，揭示了疾病进程的位置和严重程度。现有研究通常在单一疾病中仅检查少数扫视参数，使用多个单独的神经心理学测试分数来关联眼球运动行为与认知；然而，这种方法产生的结果不一致且无法推广，并且没有考虑这些疾病的认知异质性。全面的认知评估和直接的疾病间比较对于准确揭示潜在的扫视生物标志物至关重要。我们通过在一个包含五个疾病队列（阿尔茨海默病/轻度认知障碍、肌萎缩侧索硬化症、额颞叶痴呆、帕金森病和脑血管疾病；n = 391，年龄40 - 87岁）和健康对照组（n = 149，年龄42 - 87岁）的大型横断面数据集中，对12个行为参数进行特征描述来解决这些问题，这些参数是从交错的前瞻性扫视和反扫视任务中选取的，旨在稳健地描述扫视行为。这些参与者还完成了一套广泛的神经心理学测试。我们根据诊断亚组（针对阿尔茨海默病/轻度认知障碍和额颞叶痴呆）或基于神经心理学测试的认知障碍程度（所有其他队列）对每个队列进行了进一步细分。我们试图了解眼球运动参数之间的联系、它们与稳健认知测量指标的关系以及它们在疾病中的变化。我们进行了因子分析，评估12个眼球运动参数之间的相互关系，并检查四个所得因子与五个基于神经心理学的认知领域分数的相关性。然后，我们在个体参数水平上比较了上述疾病亚组与对照组之间的行为。我们推测每个潜在因子测量的是一个与特定任务相关的脑过程的完整性。值得注意的是，因子3（自愿扫视生成）和因子1（任务脱离）与注意力/工作记忆和执行功能分数显著相关。因子3还与记忆和视觉空间功能分数相关。因子2（抢先全局抑制）仅与注意力/工作记忆分数相关，而因子4（扫视指标）与任何认知领域分数均无相关性。在几个主要与反扫视相关的个体参数上的损伤随疾病队列中的认知损伤程度而变化，而在前瞻性扫视参数方面，很少有亚组与对照组不同。交错的前瞻性扫视和反扫视任务能够检测认知损伤，并且参数子集可能指示与不同认知领域相关的不同潜在过程。这表明该任务是一种敏感的范式，可以同时评估神经退行性疾病和脑血管疾病中各种临床相关的认知结构，并且可以开发成为适用于多种诊断的筛查工具。
