描述眼动参数与无视力帕金森病患者眼动功能的关系
Summary
在这里，我们提出一个方案，研究眼睛运动参数和认知功能之间的关系，在非精神病患者。实验使用眼动仪测量视觉搜索任务中的阳高音振幅和固定持续时间。随后测量了多域认知任务中与性能的相关性。
Abstract
认知障碍是帕金森病中常见的现象，对预后有影响。简单、非侵入性和客观的帕金森病认知功能测量将有助于检测早期认知衰退。作为一种生理指标，眼睛运动参数不被受试者的属性和智力所迷惑，如果与认知功能相关，则可以作为代理标记。为此，本研究探讨了眼动参数与多个领域认知测试中的表现之间的关系。在实验中，设置了一个带有眼动追踪的可视化搜索任务，要求受试者寻找嵌入在随机散落在计算机屏幕上的字母数组中的数字。数字和字母表之间的区分是一个过度学习的任务，使认知能力对眼睛运动参数的混淆效应最小化。在可视化搜索任务期间捕获并计算了平均的 saccadic 振幅和固定持续时间。认知评估电池涵盖正面执行功能、注意力、言语和视觉记忆等领域。研究发现，长期固定时间与语言流利度、视觉和言语记忆表现较差有关，从而进一步探索使用眼动参数作为帕金森病认知功能的代理标记患者。实验模式已经发现，在我们的帕金森病患者群体中是高度可容忍的，并且可以跨诊断应用于其他疾病实体，以进行类似的研究问题。
Introduction
帕金森病是典型的运动障碍;然而，这种疾病也与认知缺陷有关，而发展成痴呆症是常见的1。帕金森病认知障碍的病理生理学尚未得到很好的理解。它被认为与基于布拉克的阶段2在皮质区域的α-核素沉积有关。还提出多巴胺能和胆碱能系统退化的双重综合征导致不同的认知缺陷，预后暗示3。需要更多的研究来进一步阐明帕金森病认知障碍的确切机制。在临床方面，认知障碍的存在对预后4，5有显著影响。因此，在临床实践中评估认知功能至关重要。然而，长时间的认知评估受到患者精神和运动条件的限制。因此，需要一种非侵入性和简单的测量，能够反映疾病对认知功能的负担。
眼动异常被广泛描述为帕金森病的早期6的可检测迹象，但病理生理学甚至比认知障碍的特征更不明显。眼动的产生是通过视觉感官输入的转换，由交织的皮质和皮下网络将心形转换成到脑干中oculmotor核的信号，以产生效果7。帕金森氏症疾病在这些网络中的参与可能导致可观察到的眼睛运动异常。可能有，也许重叠的神经解剖结构，控制眼睛运动和认知功能。此外，还有研究检查其他神经退行性疾病的眼动和认知功能之间的关系8。基于这些理由，有必要探讨使用眼动参数作为帕金森病认知功能的代理标记。一项横截面研究9显示，松节振幅的降低和固定持续时间的延长与帕金森病全球认知障碍的严重程度有关。然而，缺乏关于眼动参数和特定认知领域之间相关性的数据。衡量特定认知领域（而不是一般认知状态）的意义和需要是，个体认知域在帕金森病3中通知差异预后信息，并且这些认知域由不同的神经网络。本研究旨在探讨眼动指标与不同认知功能之间的特定关系。这是建立基础的第一步，在此基础上利用眼动追踪技术开发帕金森病认知衰退的生物标志物。
实验范式由认知评价和眼动追踪任务两大部分组成。认知评估电池包括一系列认知功能，包括注意力和工作记忆、执行功能、语言、语言记忆和视觉空间功能。这5个认知领域的选择是基于运动障碍社会工作队指南对帕金森病的轻度认知障碍10，并选择了一组本地可用的认知测试，以建立评估电池。在之前关于帕金森病认知的类似眼动研究中，作者提取了眼部运动参数，而受试者从事视觉认知任务时，这些参数可能受主体的认知能力。由于本研究旨在评估眼动参数与不同认知领域之间的相关性，因此必须解决认知能力对眼睛参数的潜在混淆效应。在这方面，根据另一项眼动追踪研究改编的视觉搜索任务，被应用于捕捉受试者的眼动参数。在任务期间，受试者必须搜索多个字母干扰器之间的计算机屏幕上的单个数字。这项任务将引起交替使用眼动和视觉固定，其异常在帕金森病中被广泛描述。数字和字母的识别和区分是一项过度学习的任务，对认知功能的需求是微不足道的，因此，适合回答本研究的研究问题。根据Räsler等人11所述的规格和设计，开发了一个计算机程序。在他们的原始研究中运行在我们的眼动仪的内置软件。为本研究开发了一种内部对眼动追踪数据进行分类和分析的算法。
Protocol
Representative Results
Discussion
上述协议被设计为纵向研究的第一部分，旨在探索眼动参数作为帕金森病认知功能的替代标志物的潜在临床效用。虽然有研究，检查更多的经典眼跟踪范式，如自定进度的囊肿，反身性囊，和反囊25，26，27，视觉搜索任务在这项研究中用于测量眼睛运动参数。如前所述，此视觉搜索任务的设计至关重要，因为它必须尽量减少认…
Divulgazioni
The authors have nothing to disclose.
Acknowledgements
作者要感谢哈维·洪博士对手稿的建议。
Materials
| Computer | Intel | ||
| Computerized cognitive assessment tool | CANTAB | CANTAB Research Suite | Contains Pattern Recognition Memory, Spatial Span, and Stockings of Cambridge |
| Eye Movement Analyzer | Lab Viso Limited | https://github.com/lab-viso-limited/visual-search-analyzer | |
| Eye tracker | Tobii | Tx300 | 23 inch computer screen with resolution of 1920×1080, Sampling rate at 300Hz |
| Hong Kong List Leanrning Test | Department of Psychology, The Chinese University of Hong Kong | The Hong Kong List Learning Test (HKLLT) 2nd Edition | |
| Stroop test | Laboratory of Neuropsychology, The University of Hong Kong | Neuropsychological Measures: Normative Data for Chinese, Second Edition (Revised) | |
| Tobii Studio | Tobii | Tobii Studio version 3.2.2 | Computer programme for running the visual search task |
| Visual Search Task | Lab Viso Limited | https://www.labviso.com/#products |
Riferimenti
- Hely, M. A., Reid, W. G. J., Adena, M. A., Halliday, G. M., Morris, J. G. L. The Sydney Multicenter Study of Parkinson’s disease: The inevitability of dementia at 20 years. Movement Disorders. 23 (6), 837-844 (2008).
- Braak, H., Del Tredici, K., Bratzke, H., Hamm-Clement, J., Sandmann-Keil, D., Rüb, U. Staging of the intracerebral inclusion body pathology associated with idiopathic Parkinson’s disease (preclinical and clinical stages). Journal of Neurology. 249, 1-5 (2002).
- Williams-Gray, C. H., et al. The distinct cognitive syndromes of Parkinson’s disease: 5 year follow-up of the CamPaIGN cohort. Brain. 132 (11), 2958-2969 (2009).
- Buter, T. C., van den Hout, A., Matthews, F. E., Larsen, J. P., Brayne, C., Aarsland, D. Dementia and survival in parkinson disease: A 12-year population study. Neurology. 70 (13), 1017-1022 (2008).
- Aarsland, D., Larsen, J. P., Tandberg, E., Laake, K. Predictors of nursing home placement in Parkinson’s disease: A population-based, prospective study. Journal of the American Geriatrics Society. 48 (8), 938-942 (2000).
- Rascol, O., et al. Abnormal ocular movements in parkinson’s disease: Evidence for involvement of dopaminergic systems. Brain. 112 (5), 1193-1214 (1989).
- Orban De Xivry, J. J., Lefèvre, P. Saccades and pursuit: Two outcomes of a single sensorimotor process. Journal of Physiology. 584 (1), 11-23 (2007).
- Crawford, T. J., et al. Inhibitory control of saccadic eye movements and cognitive impairment in Alzheimer’s disease. Biological Psychiatry. 57 (9), 1052-1060 (2005).
- Archibald, N. K., Hutton, S. B., Clarke, M. P., Mosimann, U. P., Burn, D. J. Visual exploration in Parkinson’s disease and Parkinson’s disease dementia. Brain. 136 (3), 739-750 (2013).
- Litvan, I., et al. Diagnostic criteria for mild cognitive impairment in Parkinson’s disease: Movement Disorder Society Task Force guidelines. Movement Disorders. 27 (3), 349-356 (2012).
- Rösler, A., et al. Alterations of visual search strategy in Alzheimer’s disease and aging. Neuropsychology. 14 (3), 398-408 (2000).
- Hughes, A. J., Daniel, S. E., Kilford, L., Lees, A. J. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: A clinico-pathological study of 100 cases. Journal of Neurology Neurosurgery and Psychiatry. 55 (3), 181-184 (1992).
- Chiu, H. F. K., Lee, H. C., Chung, W. S., Kwong, P. K. Reliability and Validity of the Cantonese Version of Mini-Mental State Examination-A Preliminary Study. Hong Kong Journal of Psychiatry. 4 (2), 25 (1994).
- Wong, A., et al. The validity, reliability and clinical utility of the Hong Kong Montreal Cognitive Assessment (HK-MoCA) in patients with cerebral small vessel disease. Dementia and Geriatric Cognitive Disorders. 28 (1), 81-87 (2009).
- Fahn, S., Elton, R. Members of the UPDRS Development Committee. Unified Parkinson’s disease rating scale. Recent Development in Parkinson’s Disease. 2, 293-304 (1987).
- Hoehn, M. M., Yahr, M. D. Parkinsonism: onset, progression, and mortality. Neurology. 17 (5), 427-427 (1967).
- Wu, P. C., Chang, L. Psychometric properties of the Chinese version of the Beck Depression Inventory-II using the Rasch model. Measurement and Evaluation in Counseling and Development. 41 (1), 13-31 (2008).
- Chiu, H. F., et al. The modified Fuld Verbal Fluency Test: a validation study in Hong Kong. The journals of gerontology. Series B, Psychological sciences and social sciences. 52 (5), 247-250 (1997).
- Chan, A. S., Kwok, I. Hong Kong list learning test: manual and preliminary norm. Hong Kong: Department of Psychological and Clinical Psychology Center. , (1999).
- Robbins, T. W., James, M., Owen, A. M., Sahakian, B. J., McInnes, L., Rabbitt, P. Cambridge Neuropsychological Test Automated Battery (CANTAB): A Factor Analytic Study of a Large Sample of Normal Elderly Volunteers. Dementia and Geriatric Cognitive Disorders. 5 (5), 266-281 (1994).
- Lee, T. M. C., Wang, K. . Neuropsychological Measures: Normative Data for Chinese. , (2010).
- Birant, D., Kut, A. ST-DBSCAN: An algorithm for clustering spatial-temporal data. Data and Knowledge Engineering. 60 (1), 208-221 (2007).
- Wong, O. W., et al. Eye movement parameters and cognitive functions in Parkinson’s disease patients without dementia. Parkinsonism and Related Disorders. 52, 43-48 (2018).
- Muslimovic, D., Post, B., Speelman, J. D., Schmand, B. Cognitive profile of patients with newly diagnosed Parkinson disease. Neurology. 65 (8), 1239-1245 (2005).
- Winograd-Gurvich, C., Georgiou-Karistianis, N., Fitzgerald, P. B., Millist, L., White, O. B. Self-paced saccades and saccades to oddball targets in Parkinson’s disease. Brain Research. 1106 (1), 134-141 (2006).
- Briand, K. A., Strallow, D., Hening, W., Poizner, H., Sereno, A. B. Control of voluntary and reflexive saccades in Parkinson’s disease. Experimental Brain Research. 129 (1), 38-48 (1999).
- Rivaud-Péchoux, S., Vidailhet, M., Brandel, J. P., Gaymard, B. Mixing pro- and antisaccades in patients with parkinsonian syndromes. Brain. 130 (1), 256-264 (2007).
- Perneczky, R., Ghosh, B. C. P., Hughes, L., Carpenter, R. H. S., Barker, R. A., Rowe, J. B. Saccadic latency in Parkinson’s disease correlates with executive function and brain atrophy, but not motor severity. Neurobiology of Disease. 43 (1), 79-85 (2011).
- Matsumoto, H., et al. Small saccades restrict visual scanning area in Parkinson’s disease. Movement Disorders. 26 (9), 1619-1626 (2011).
- MacAskill, M. R., Anderson, T. J., Jones, R. D. Adaptive modification of saccade amplitude in Parkinson’s disease. Brain. 125 (7), 1570-1582 (2002).
- Salvucci, D. D., Goldberg, J. H. Identifying fixations and saccades in eye-tracking protocols. Proceedings of the 2000 symposium on Eye tracking research & applications. , 71-78 (2000).
- Rana, A. Q., Kabir, A., Dogu, O., Patel, A., Khondker, S. Prevalence of blepharospasm and apraxia of eyelid opening in patients with parkinsonism, cervical dystonia and essential tremor. European Neurology. 68 (5), 318-321 (2012).
