Singh Arun, Cole Rachel C, Espinoza Arturo I, Evans Aron, Cao Scarlett, Cavanagh James F, Narayanan Nandakumar S
Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, USA.
Department of Neurology, University of Iowa, Iowa City, IA, USA.
NPJ Parkinsons Dis. 2021 Feb 15;7(1):14. doi: 10.1038/s41531-021-00158-x.
Patients with Parkinson's disease (PD) can have significant cognitive dysfunction; however, the mechanisms for these cognitive symptoms are unknown. Here, we used scalp electroencephalography (EEG) to investigate the cortical basis for PD-related cognitive impairments during interval timing, which requires participants to estimate temporal intervals of several seconds. Time estimation is an ideal task demand for investigating cognition in PD because it is simple, requires medial frontal cortical areas, and recruits basic executive processes such as working memory and attention. However, interval timing has never been systematically studied in PD patients with cognitive impairments. We report three main findings. First, 71 PD patients had increased temporal variability compared to 37 demographically matched controls, and this variability correlated with cognitive dysfunction as measured by the Montreal Cognitive Assessment (MOCA). Second, PD patients had attenuated ~4 Hz EEG oscillatory activity at midfrontal electrodes in response to the interval-onset cue, which was also predictive of MOCA. Finally, trial-by-trial linear mixed-effects modeling demonstrated that cue-triggered ~4 Hz power predicted subsequent temporal estimates as a function of PD and MOCA. Our data suggest that impaired cue-evoked midfrontal ~4 Hz activity predicts increased timing variability that is indicative of cognitive dysfunction in PD. These findings link PD-related cognitive dysfunction with cortical mechanisms of cognitive control, which could advance novel biomarkers and neuromodulation for PD.
帕金森病（PD）患者可能存在显著的认知功能障碍；然而，这些认知症状的机制尚不清楚。在此，我们使用头皮脑电图（EEG）来研究在间隔计时期间与PD相关的认知障碍的皮质基础，这要求参与者估计几秒的时间间隔。时间估计是研究PD认知的理想任务需求，因为它简单，需要内侧额叶皮质区域，并涉及诸如工作记忆和注意力等基本执行过程。然而，间隔计时从未在有认知障碍的PD患者中进行过系统研究。我们报告了三个主要发现。首先，与37名人口统计学匹配的对照相比，71名PD患者的时间变异性增加，并且这种变异性与通过蒙特利尔认知评估（MOCA）测量的认知功能障碍相关。其次，PD患者在额中电极处对间隔开始提示的4Hz EEG振荡活动减弱，这也可预测MOCA。最后，逐次试验线性混合效应模型表明，提示触发的4Hz功率作为PD和MOCA的函数预测随后的时间估计。我们的数据表明，提示诱发的额中~4Hz活动受损预示着计时变异性增加，这表明PD患者存在认知功能障碍。这些发现将与PD相关的认知功能障碍与认知控制的皮质机制联系起来，这可能推动针对PD的新型生物标志物和神经调节研究。
