Diminished Activation of Motor Working-Memory Networks in Parkinson's Disease

Parkinson's disease (PD) is characterized by typical extrapyramidal motor features and increasingly recognized non-motor symptoms such as working memory (WM) deficits. Using functional magnetic resonance imaging (fMRI), we investigated differences in neuronal activation during a motor WM task in 23 non-demented PD patients and 23 age- and gender-matched healthy controls. Participants had to memorize and retype variably long visuo-spatial stimulus sequences after short or long delays (immediate or delayed serial recall). PD patients showed deficient WM performance compared to controls, which was accompanied by reduced encoding-related activation in WM-related regions. Mirroring slower motor initiation and execution, reduced activation in motor structures such as the basal ganglia and superior parietal cortex was detected for both immediate and delayed recall. Increased activation in limbic, parietal and cerebellar regions was found during delayed recall only. Increased load-related activation for delayed recall was found in the posterior midline and the cerebellum. Overall, our results demonstrate that impairment of WM in PD is primarily associated with a widespread reduction of task-relevant activation, whereas additional parietal, limbic and cerebellar regions become more activated relative to matched controls. While the reduced WM-related activity mirrors the deficient WM performance, the additional recruitment may point to either dysfunctional compensatory strategies or detrimental crosstalk from “default-mode” regions, contributing to the observed impairment.

帕金森病（Parkinson's disease, PD）以典型的锥体外系运动特征为核心临床表现，其日益受到学界关注的非运动症状亦包含工作记忆（working memory, WM）缺损。本研究采用功能磁共振成像（functional magnetic resonance imaging, fMRI）技术，纳入23名无痴呆的PD患者与23名年龄、性别匹配的健康对照者，探究二者在完成运动型WM任务时的神经元激活差异。受试者需在短时或长时延迟（即时系列回忆与延迟系列回忆）范式下，记忆并重新输入长度可变的视觉空间刺激序列。与健康对照相比，PD患者的WM表现存在显著缺损，且该缺损伴随WM相关脑区内编码相关激活水平的降低。与运动启动及执行速度减慢的临床表型相呼应，患者在即时回忆与延迟回忆任务中，基底神经节（basal ganglia）、顶上小叶皮层（superior parietal cortex）等运动相关脑区的激活均出现减弱。仅在延迟回忆任务中，研究者观测到边缘叶、顶叶及小脑区域的激活水平升高；后中线区域与小脑则在延迟回忆任务中表现出与任务负荷相关的激活增强。总体而言，本研究结果表明，PD患者的WM缺损主要与任务相关激活的广泛降低相关；而相较于匹配对照，额外被激活的顶叶、边缘叶及小脑区域的激活水平升高。尽管工作记忆相关活动的降低可直接反映缺损的WM表现，但额外被募集的脑区激活可能指向功能失调的代偿策略，或是来自“默认模式”脑区（default-mode regions）的有害串扰，二者共同参与并促成了观测到的工作记忆缺损进程。