MacDonald Hayley J, Brittain John-Stuart, Spitzer Bernhard, Hanslmayr Simon, Jenkinson Ned
School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham B15 2TT, UK.
Centre for Human Brain Health, University of Birmingham, Birmingham B15 2TT, UK.
Brain Commun. 2019;1(1):fcz040. doi: 10.1093/braincomms/fcz040. Epub 2019 Dec 4.
There is an increasing recognition of the significant non-motor symptoms that burden people with Parkinson's disease. As such, there is a pressing need to better understand and investigate the mechanisms underpinning these non-motor deficits. The electrical activity within the brains of people with Parkinson's disease is known to exhibit excessive power within the beta range (12-30 Hz), compared with healthy controls. The weight of evidence suggests that this abnormally high level of beta power is the cause of bradykinesia and rigidity in Parkinson's disease. However, less is known about how the abnormal beta rhythms seen in Parkinson's disease impact on non-motor symptoms. In healthy adults, beta power decreases are necessary for successful episodic memory formation, with greater power decreases during the encoding phase predicting which words will subsequently be remembered. Given the raised levels of beta activity in people with Parkinson's disease, we hypothesized that the necessary decrease in power during memory encoding would be diminished and that this would interfere with episodic memory formation. Accordingly, we conducted a cross-sectional, laboratory-based experimental study to investigate whether there was a direct relationship between decreased beta modulation and memory formation in Parkinson's disease. Electroencephalography recordings were made during an established memory-encoding paradigm to examine brain activity in a cohort of adults with Parkinson's disease ( = 28, 20 males) and age-matched controls ( = 31, 18 males). The participants with Parkinson's disease were aged 65 ± 6 years, with an average disease duration of 6 ± 4 years, and tested on their normal medications to avoid the confound of exacerbated motor symptoms. Parkinson's disease participants showed impaired memory strength ( = 0.023) and reduced beta power decreases ( = 0.014) relative to controls. Longer disease duration was correlated with a larger reduction in beta modulation during encoding, and a concomitant reduction in memory performance. The inability to sufficiently decrease beta activity during semantic processing makes it a likely candidate to be the central neural mechanism underlying this type of memory deficit in Parkinson's disease. These novel results extend the notion that pathological beta activity is causally implicated in the motor and (lesser appreciated) non-motor deficits inherent to Parkinson's disease. These findings provide important empirical evidence that should be considered in the development of intelligent next-generation therapies.
帕金森病患者所承受的显著非运动症状越来越受到关注。因此，迫切需要更好地理解和研究这些非运动功能障碍背后的机制。与健康对照相比，已知帕金森病患者大脑内的电活动在β频段（12 - 30赫兹）表现出过高的功率。大量证据表明，这种异常高水平的β功率是帕金森病运动迟缓及僵硬的原因。然而，对于帕金森病中出现的异常β节律如何影响非运动症状，人们了解较少。在健康成年人中，β功率降低对于成功的情景记忆形成是必要的，编码阶段功率降低幅度越大，预测随后哪些单词会被记住的可能性就越大。鉴于帕金森病患者的β活动水平升高，我们推测记忆编码过程中功率的必要降低会减弱，这将干扰情景记忆的形成。因此，我们进行了一项基于实验室的横断面实验研究，以调查帕金森病中β调制降低与记忆形成之间是否存在直接关系。在既定的记忆编码范式期间进行脑电图记录，以检查一组帕金森病成年人（n = 28，20名男性）和年龄匹配的对照组（n = 31，18名男性）的大脑活动。帕金森病参与者的年龄为65±6岁，平均病程为6±4年，并在正常用药情况下进行测试，以避免运动症状加重的混淆因素。与对照组相比，帕金森病参与者表现出记忆强度受损（p = 0.023）和β功率降低幅度减小（p = 0.014）。病程越长，编码期间β调制的降低幅度越大，同时记忆表现也随之降低。在语义处理过程中无法充分降低β活动，使其很可能成为帕金森病中这类记忆缺陷的核心神经机制。这些新结果扩展了病理性β活动与帕金森病固有的运动和（较少被认识到的）非运动缺陷存在因果关系的概念。这些发现提供了重要的实证证据，在开发智能下一代疗法时应予以考虑。
