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帕金森病的时间工作记忆损伤:行为和脑影像研究
Alternative TitleImpaired Temporal Working Memorv in Parkinson's Disease: Evidence from Behavioral and Neuroimaging Studies
叶铮
Subtype博士
Thesis Advisor叶铮
2019-06
Degree Grantor中国科学院大学
Place of Conferral中国科学院心理研究所
Degree Name理学博士
Keyword帕金森病 认知障碍 时间工作记忆 序列工作记忆 功能磁共振成像
Abstract

时间是构成这个世界的重要维度,万事万物之间都离不开一定的时间顺序。大脑如何在工作记忆中表征和更新多个事件的先后顺序是人们长久以来探讨的科学问题,这涉及到时间工作记忆这一概念。与视空间工作记忆关注客体视空间特征的加工不同,时间工作记忆关注多个客体之间时间关系的表征和加工。

帕金森病(PD)是中老年人群体中常见的神经退行性疾病。作为一种多系统障碍病,PD不仅引起震颤、运动迟缓、肌肉僵直等运动症状,也会引起包括认知障碍在内的多种非运动症状。工作记忆损伤是PD患者认知障碍的主要特征之一。在以下四项研究中,我们结合神经心理学测验、心理物理法和神经影像技术,从行为和脑成像两方面,探究PD患者时间工作记忆的损伤。

研究一应用数字顺背测验、倒背测验和序背测验等工作记忆测验,在非痴呆的早期PD患者中识别时间工作记忆的损伤。其中顺背测验测量受试者编码和保持表征的能力,倒背测验和序背测验测量受试者编码、保持和操作表征的能力。研究一的结果表明,非痴呆的早期PD患者存在时间工作记忆的损伤,这一损伤特异表现为操作时间序列的能力下降,但编码和保持时间序列的能力没有受损。研究二对非痴呆PD患者和健康对照者在工作记忆测验中的错误进行分类,探究PD患者在时间工作记忆中的认知特点。错误类型分移位和替换两大类,其中移位错误包括前移错误、后移错误,前移错误之后会发生fill-in错误或infill错误;替换错误包括重复替换错误和非重复替换错误。研究二的结果表明,非痴呆PD患者在更新表征时会发生更多的移位错误,包括前移错误和fill-in错误,在保持表征时错误发生率与健康对照者无显著差异。前移错误的增加说明PD患者在操作表征时倾向于将项目更早地提取出来;fill-in错误的增加说明PD患者链接机制出现了缺损,这一机制与时间工作记忆中表征的操作有关。研究三运用功能磁共振成像技术和计算机化的数字序背任务,在健康人群中探究时间工作记忆的神经相关物,结果表明表征的更新涉及前额叶、后顶叶、丘脑、小脑等多区域的激活;相比较于健康青年人,健康老年人在时间工作记忆任务中,前额叶和后顶叶区域均有显著的过激活;在前额叶、后顶叶与辅助运动区的功能连接出现下降。研究四运用神经影像技术和计算机化的数字序背任务,揭示了PD新发患者时间工作记忆损伤的神经相关物。结果表明PD患者在操作时间工作记忆表征时,背外侧前额叶和后顶叶均呈现过激活;相比于健康老年人,PD患者抑制默认网络区域活动的能力显著下降。

综上所述,非痴呆的PD患者在时间工作记忆中保持表征的能力完好,而操作表征的能力显著下降,这一特异性缺损与他们的链接机制缺损有关。健康人对时间工作记忆表征进行操作时,前额叶、后顶叶、丘脑和小脑区域会呈现显著激活。PD患者时间工作记忆的损伤与背外侧前额叶及后顶叶区域的过激活、默认网络的抑制能力下降有关。

Other Abstract

How brains represent and manipulate a sequence of multiple objects in working memory is still an open question. Different from visuospatial working memory which focuses on the operation of objects' visuospatial features, temporal working memory focuses on the processing of temporal relations among multiple objects.

Parkinson's disease (PD) is a common neurodegenerative disease in elderly people. PD not only causes motor symptoms such as tremor, bradykinesia and rigidity, but also causes a variety of non-motor symptoms including cognitive impairment. Working memory impairment is one feature of the cognitive impairment in patients with PD. In the following four studies, we used neuropsychological and cognitive tests, psychophysiology methods and neuroimaging to investigate the neural correlates of temporal working memory impairment in patients with PD.

In the first study, we detected temporal working memory impairment in nondemented early-stage PD patients by using the digit span forward and backward tests, and the Adaptive Digit Ordering Test (DOT-A). The digit span forward test measured the ability to encode maintain the representations, the digit span backward test and DOT-A measured the ability to encode, maintain and manipulate the representations. The ability to manipulate temporal working memory representations was impaired in PD, while the ability to encode and maintain the representations was preserved. In the second study, we categorized the errors in working memory tests in patients with PD and healthy control subjects. Errors were firstly classified as transposition or item errors. Transposition errors were divided into anticipation and postponement errors, and fill-in erros or infill errors occurred after anticipation errors. Item errors were divided into repetition and non-repetition errors. Patients with PD showed more transposition errors, including anticipation errors and fill-in errors when manipulating the representations, but not when maintaining the representations. It suggested that PD patients tended to recall the items too early when manipulated the representations, and the chaining mechanism involved in the manipulation of serial order was impaired in patients with PD. In the third study, we applied functional MRl and computerized digit ordering task to investigate the neural correlates of temporal working memory in healthy people. We found that the manipulation of temporal working memory involved the activations of the prefrontal cortex, posterior parietal cortex, thalamus, and cerebellum. Compare to young adults, older aduldts were overactivated in the prefrontal cortex and parietal cortex. The functional connectivity between the supplementary motor area and the prefrontal/parietal cortex was weaker in older adults. In the fourth study, we investigated the neural correlates of temporal working memory impairment in PD by using functional MRI and computerized digit ordering task. The dorsolateral prefrontal cortex was over-activated when PD patients manipulated the representations. The functional connectivity between the dorsolateral prefrontal cortex and visual cortex became weaker compared to healthy controls.

In conclusions, the ability to manipulate temporal working memory representations was impaired in nondemented PD, while the ability to encode and maintain the representations was spared, and this selectively impairment related to the deficits of chaining mechanism. Manipulating temporal working memory representations involved the activations of the prefrontal cortex, posterior parietal cortex, thalamus, and cerebellum. The over-activation of the prefrontal cortex and posterior parietal cortex, and the reduced default mode network deactivation involved in the impairment of temporal working memory in PD.

Pages124
Language中文
Document Type学位论文
Identifierhttp://ir.psych.ac.cn/handle/311026/29302
Collection健康与遗传心理学研究室
Recommended Citation
GB/T 7714
叶铮. 帕金森病的时间工作记忆损伤:行为和脑影像研究[D]. 中国科学院心理研究所. 中国科学院大学,2019.
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