Department of Neuroscience, University of British Columbia, Vancouver, BC, Canada.
Neuroscience. 2010 Apr 14;166(4):1110-8. doi: 10.1016/j.neuroscience.2010.01.012. Epub 2010 Jan 13.
Neuroimaging studies in Parkinson's disease (PD) have previously demonstrated several regions of hypo- and hyper-activation during voluntary movement. How these patterns of amplitude changes at multiple discrete foci relate to changes within functional networks recruited by a given task is unclear. Changes in both amplitude and connectivity have both been individually shown within the striato-thalamo-cortical (STC) loop in PD, as well as other regions, most consistently in the cerebellum and primary motor cortex. We have previously shown overactivation of the cerebellum and motor cortex in PD subjects off medication during a visuo-motor tracking task performed at three frequencies. Here, we show that this change in activation amplitude is also accompanied by significant changes in functional connectivity between regions of interest (ROIs), with enhanced connectivity within the cerebello-thalamo-cortical (CTC) loop as well as increased inter-hemispheric communication between several basal ganglia structures. Although changes in activation amplitude were influenced by the frequency of movement performed in the tracking task, functional connectivity changes were robustly present across all three task frequencies performed, suggesting that functional connectivity analysis in PD may be a more sensitive means of detecting plastic changes which are relatively invariant to the particulars of the experimental task. Additionally, we demonstrate amplitude and connectivity changes in structures that are typically active during the resting state, or "default-mode," in PD. Unlike in STC/CTC loops, where the direction of change was the same for amplitude and connectivity, default-mode regions showed increased amplitude but decreased connectivity. Our results further support that the CTC is recruited in PD to compensate for dysfunctional basal ganglia circuits, and that this recruitment involves both amplitude and connectivity changes. The differing relationship between amplitude and connectivity changes within individual loops highlights the importance of jointly examining them in order to fully elucidate functional changes in Parkinson's disease.
神经影像学研究表明，在帕金森病（PD）患者进行自主运动时，多个区域存在活动过度和活动不足。这些在多个离散焦点处的幅度变化模式与特定任务所募集的功能网络中的变化有何关系尚不清楚。在 PD 患者的纹状体-丘脑-皮质（STC）回路以及其他区域（最常见于小脑和初级运动皮层）中，已经分别显示出幅度和连接性的变化。我们之前已经表明，在进行视觉运动跟踪任务时，PD 患者在药物治疗下，小脑和运动皮层过度激活，且在三个频率下进行。在这里，我们表明，这种激活幅度的变化也伴随着感兴趣区域（ROI）之间的功能连接的显著变化，小脑-丘脑-皮质（CTC）回路中的连接增强，以及几个基底节结构之间的半球间通信增加。尽管激活幅度的变化受到跟踪任务中运动频率的影响，但功能连接变化在所有三个任务频率下均存在，这表明 PD 中的功能连接分析可能是一种更敏感的方法，可以检测相对不变的实验任务的特定情况的可塑性变化。此外，我们证明了在 PD 中，在静息状态或“默认模式”下通常活跃的结构中的幅度和连接变化。与 STC/CTC 回路不同，幅度和连接的变化方向相同，默认模式区域显示出幅度增加但连接性降低。我们的结果进一步支持 CTC 在 PD 中被募集以补偿功能失调的基底节回路，并且这种募集涉及幅度和连接性的变化。单个回路中幅度和连接性变化之间的不同关系强调了联合检查它们的重要性，以便充分阐明帕金森病中的功能变化。
