Lang Stefan, Gan Liu Shi, Yoon Eun Jin, Hanganu Alexandru, Kibreab Mekale, Cheetham Jenelle, Hammer Tracy, Kathol Iris, Sarna Justyna, Martino Davide, Monchi Oury
Cumming School of Medicine, Hotchkiss Brain Institute, Calgary, AB, Canada.
Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada.
Front Neurol. 2020 Dec 21;11:584374. doi: 10.3389/fneur.2020.584374. eCollection 2020.
Mild cognitive impairment is a common non-motor symptom of Parkinson's disease (PD-MCI) and has minimal treatment options. In this double-blind, randomized, sham-controlled trial, we assessed the effect of repeated sessions of intermittent theta-burst stimulation over the left dorsolateral prefrontal cortex on cognition and brain connectivity in subjects with PD-MCI. Forty-one subjects were randomized to receive real ( = 21) or sham stimulation ( = 20). All subjects underwent neuropsychological assessments before, 1 day, and 1 month after stimulation. Subjects also underwent resting-state functional magnetic resonance imaging before and 48 h after stimulation. The primary outcome was the change in the cognitive domain (executive function, attention, memory, language, and visuospatial abilities) z-scores across time. There was an insignificant effect on cognitive domain z-scores across time when comparing real with sham stimulation and correcting for multiple comparisons across cognitive domains ( > 0.05 Bonferroni correction). However, the real stimulation group demonstrated a trend toward improved executive functioning scores at the 1-month follow-up compared with sham ( < 0.05 uncorrected). After real stimulation, the connectivity of the stimulation site showed decreased connectivity to the left caudate head. There was no change in connectivity within or between the stimulation network (a network of cortical regions connected to the stimulation site) and the striatal network. However, higher baseline connectivity between the stimulation network and the striatal network was associated with improved executive function scores at 1 month. These results suggest that intermittent theta-burst stimulation over the dorsolateral prefrontal cortex in subjects with PD-MCI has minimal effect on cognition compared with sham, although there were trends toward improved executive function. This intervention may be more effective in subjects with higher baseline connectivity between the stimulation network and the striatal network. This trial supports further investigation focusing on executive function and incorporating connectivity-based targeting. www.ClinicalTrials.gov, identifier NCT03243214.
轻度认知障碍是帕金森病的一种常见非运动症状（帕金森病轻度认知障碍），且治疗选择极少。在这项双盲、随机、假刺激对照试验中，我们评估了对帕金森病轻度认知障碍患者左侧背外侧前额叶皮层进行重复间歇性θ波爆发刺激对认知和脑连接性的影响。41名受试者被随机分为接受真刺激（n = 21）或假刺激（n = 20）两组。所有受试者在刺激前、刺激后1天和1个月均接受神经心理学评估。受试者在刺激前和刺激后48小时还接受了静息态功能磁共振成像检查。主要结局是认知领域（执行功能、注意力、记忆、语言和视觉空间能力）z分数随时间的变化。在比较真刺激与假刺激并对各认知领域进行多重比较校正后，认知领域z分数随时间的变化无显著影响（经Bonferroni校正，P>0.05）。然而，与假刺激组相比，真刺激组在1个月随访时执行功能得分有改善趋势（未校正，P<0.05）。真刺激后，刺激部位与左侧尾状核头部的连接性降低。刺激网络（与刺激部位相连的皮层区域网络）内部或之间以及与纹状体网络之间的连接性没有变化。然而，刺激网络与纹状体网络之间较高的基线连接性与1个月时执行功能得分的改善相关。这些结果表明，与假刺激相比，对帕金森病轻度认知障碍患者背外侧前额叶皮层进行间歇性θ波爆发刺激对认知的影响极小，尽管有执行功能改善的趋势。这种干预在刺激网络与纹状体网络之间基线连接性较高的受试者中可能更有效。该试验支持进一步开展聚焦于执行功能并纳入基于连接性靶向的研究。ClinicalTrials.gov，标识符NCT03243214。
