CIBIT - Coimbra Institute for Biomedical Imaging and Translational Research, University of Coimbra, Coimbra, Portugal.
Faculty of Psychology and Education Sciences, University of Coimbra, Coimbra, Portugal.
Orphanet J Rare Dis. 2019 Nov 8;14(1):246. doi: 10.1186/s13023-019-1218-y.
This study aims to test response inhibition in premanifest Huntington's disease individuals (Pre-HD), in the context of a saccadic paradigm with working memory demands and fronto-executive load as a way to measure inhibitory control deficits and impulsive behavior in Huntington's disease (HD).
The oculomotor function of 15 Pre-HD and 22 Control individuals was assessed using an experimental paradigm comprising four horizontal saccadic tasks: prosaccade (PS), antisaccade (AS), 1- or 2-back memory prosaccade (MPS), and 1- or 2-back memory antisaccade (MAS). Success rate, latency, directional and timing errors were calculated for each task. A comprehensive battery of neuropsychological tests was also used to assess the overall cognitive functioning of study participants. Statistical correlations between oculomotor, clinical and cognitive measures were computed for the Pre-HD group.
Pre-HD participants showed reduced success rate in the AS task, increased direction errors in the AS and MAS tasks and decreased latency in the MAS task when compared to Controls, despite presenting similar executive and memory scores in the conventional neuropsychological tests applied. Significant associations were identified between specific AS and MAS parameters and disease-related measures, cognitive skills and other oculomotor results of Pre-HD participants.
Our results show that oculomotor performance in premanifest Huntington's disease deteriorates once inhibitory control, working memory and/or fronto-executive load are added to the task. A more automatic pattern of performance, including a faster response time and directionally erroneous eye movements were detected in the oculomotor behavior of the Pre-HD group-these alterations were significantly correlated with disease stage and cognitive status. Our saccadic paradigm was able to capture impulsivity and inhibitory control deficits in a group of Pre-HD individuals on average far from symptom onset, thus holding the potential to identify the earliest disease-related changes.
本研究旨在测试处于亨廷顿病前期（Pre-HD）的个体的反应抑制，采用扫视范式，结合工作记忆需求和前额执行负荷，以衡量亨廷顿病（HD）中的抑制控制缺陷和冲动行为。
使用包含四个水平扫视任务的实验范式评估 15 名 Pre-HD 和 22 名对照个体的眼动功能：正扫视（PS）、反扫视（AS）、1 或 2 背记忆正扫视（MPS）和 1 或 2 背记忆反扫视（MAS）。计算了每个任务的成功率、潜伏期、方向和时间误差。还使用了一套全面的神经心理学测试来评估研究参与者的整体认知功能。计算了 Pre-HD 组的眼动、临床和认知测量之间的统计相关性。
与对照组相比，Pre-HD 参与者在 AS 任务中的成功率降低，在 AS 和 MAS 任务中的方向误差增加，在 MAS 任务中的潜伏期降低，尽管在应用的常规神经心理学测试中表现出相似的执行和记忆分数。在 Pre-HD 参与者中，特定的 AS 和 MAS 参数与疾病相关测量、认知技能和其他眼动结果之间存在显著关联。
我们的研究结果表明，当在任务中增加抑制控制、工作记忆和/或前额执行负荷时，处于亨廷顿病前期的个体的眼动表现会恶化。在 Pre-HD 组的眼动行为中，检测到一种更自动的表现模式，包括更快的反应时间和方向错误的眼球运动——这些改变与疾病阶段和认知状态显著相关。我们的扫视范式能够在平均远未出现症状的 Pre-HD 个体中捕捉到冲动和抑制控制缺陷，因此有可能识别出与疾病相关的最早变化。
