Solstrand Dahlberg Linda, Lungu Ovidiu, Doyon Julien
Department of Neurology & Neurosurgery, McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
Department of Psychiatry, University of Montreal, Montreal, QC, Canada.
Front Neurol. 2020 Feb 27;11:127. doi: 10.3389/fneur.2020.00127. eCollection 2020.
Parkinson's disease (PD) results in both motor and non-motor symptoms. Traditionally, the underlying mechanism of PD has been linked to neurodegeneration of the basal ganglia. Yet it does not adequately account for the non-motor symptoms of the disease, suggesting that other brain regions may be involved. One such region is the cerebellum, which is known to be involved, together with the basal ganglia, in both motor and non-motor functions. Many studies have found the cerebellum to be hyperactive in PD patients, a finding that is seldom discussed in detail, and warrants further examination. The current study thus aims to examine quantitively the current literature on the cerebellar involvement in both motor and non-motor functioning in PD. A meta-analysis of functional neuroimaging literature was conducted with Seed-based D mapping. Only the studies testing functional activation in response to motor and non-motor paradigms in PD and healthy controls (HC) were included in the meta-analysis. Separate analyses were conducted by including only studies with non-motor paradigms, as well as meta-regressions with UPDRS III scores and disease duration. A total of 57 studies with both motor and non-motor paradigms fulfilled our inclusion criteria and were included in the meta-analysis, which revealed hyperactivity in Crus I-II and vermal III in PD patients compared to HC. An analysis including only studies with cognitive paradigms revealed a cluster of increased activity in PD patients encompassing lobule VIIB and VIII. Another meta-analysis including the only 20 studies that employed motor paradigms did not reveal any significant group differences. However, a descriptive analysis of these studies revealed that 60% of them reported cerebellar hyperactivations in PD and included motor paradigm with significant cognitive task demands, as opposed to 40% presenting the opposite pattern and using mainly force grip tasks. The meta-regression with UPDRS III scores found a negative association between motor scores and activation in lobule VI and vermal VII-VIII. No correlation was found with disease duration. The present findings suggest that one of the main cerebellar implications in PD is linked to cognitive functioning. The negative association between UPDRS scores and activation in regions implicated in motor functioning indicate that there is less involvement of these areas as the disease severity increases. In contrast, the lack of correlation with disease duration seems to indicate that the cerebellar activity may be a compensatory mechanism to the dysfunctional basal ganglia, where certain sub-regions of the cerebellum are employed to cope with motor demands. Yet future longitudinal studies are needed to fully address this possibility.
帕金森病（PD）会导致运动和非运动症状。传统上，PD的潜在机制与基底神经节的神经退行性变有关。然而，它并不能充分解释该疾病的非运动症状，这表明其他脑区可能也参与其中。其中一个这样的区域是小脑，已知它与基底神经节一起参与运动和非运动功能。许多研究发现PD患者的小脑过度活跃，这一发现很少被详细讨论，值得进一步研究。因此，本研究旨在定量考察当前关于小脑在PD的运动和非运动功能中所起作用的文献。采用基于种子点的D映射对功能性神经影像学文献进行了荟萃分析。荟萃分析仅纳入了测试PD患者和健康对照（HC）对运动和非运动范式反应的功能激活的研究。通过仅纳入非运动范式的研究以及使用统一帕金森病评定量表（UPDRS）III评分和病程进行荟萃回归分析。共有57项包含运动和非运动范式的研究符合纳入标准并被纳入荟萃分析，结果显示与HC相比，PD患者的小脑 Crus I-II和蚓部III过度活跃。仅纳入认知范式研究的分析显示，PD患者中一组包括小叶VIIB和VIII的活动增加。另一项仅对采用运动范式的20项研究进行的荟萃分析未发现任何显著的组间差异。然而，对这些研究的描述性分析显示，其中60%的研究报告了PD患者的小脑过度激活，且包括具有显著认知任务需求的运动范式，而40%的研究呈现相反模式，主要使用力量抓握任务。UPDRS III评分的荟萃回归发现运动评分与小叶VI和蚓部VII-VIII的激活之间存在负相关。未发现与病程相关。目前的研究结果表明，小脑在PD中的主要影响之一与认知功能有关。UPDRS评分与运动功能相关区域激活之间的负相关表明，随着疾病严重程度增加，这些区域的参与度降低。相比之下，与病程缺乏相关性似乎表明小脑活动可能是对功能失调的基底神经节的一种代偿机制，其中小脑的某些亚区域被用来应对运动需求。然而，未来需要进行纵向研究来充分探讨这种可能性
