Mizrahi-Kliger Aviv D, Kaplan Alexander, Israel Zvi, Deffains Marc, Bergman Hagai
Department of Neurobiology, Institute of Medical Research Israel-Canada, Hadassah Medical School, The Hebrew University of Jerusalem, 91120 Jerusalem, Israel;
Department of Neurobiology, Institute of Medical Research Israel-Canada, Hadassah Medical School, The Hebrew University of Jerusalem, 91120 Jerusalem, Israel.
Proc Natl Acad Sci U S A. 2020 Jul 21;117(29):17359-17368. doi: 10.1073/pnas.2001560117. Epub 2020 Jul 7.
Sleep disorders are among the most debilitating comorbidities of Parkinson's disease (PD) and affect the majority of patients. Of these, the most common is insomnia, the difficulty to initiate and maintain sleep. The degree of insomnia correlates with PD severity and it responds to treatments that decrease pathological basal ganglia (BG) beta oscillations (10-17 Hz in primates), suggesting that beta activity in the BG may contribute to insomnia. We used multiple electrodes to record BG spiking and field potentials during normal sleep and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism in nonhuman primates. MPTP intoxication resulted in severe insomnia with delayed sleep onset, sleep fragmentation, and increased wakefulness. Insomnia was accompanied by the onset of nonrapid eye movement (NREM) sleep beta oscillations that were synchronized across the BG and cerebral cortex. The BG beta oscillatory activity was associated with a decrease in slow oscillations (0.1-2 Hz) throughout the cortex, and spontaneous awakenings were preceded by an increase in BG beta activity and cortico-BG beta coherence. Finally, the increase in beta oscillations in the basal ganglia during sleep paralleled decreased NREM sleep, increased wakefulness, and more frequent awakenings. These results identify NREM sleep beta oscillation in the BG as a neural correlate of PD insomnia and suggest a mechanism by which this disorder could emerge.
睡眠障碍是帕金森病（PD）最使人衰弱的合并症之一，影响着大多数患者。其中，最常见的是失眠，即难以开始和维持睡眠。失眠程度与PD严重程度相关，且对降低病理性基底神经节（BG）β振荡（灵长类动物中为10 - 17赫兹）的治疗有反应，这表明BG中的β活动可能导致失眠。我们使用多个电极在正常睡眠期间以及在非人类灵长类动物中由1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的帕金森症模型中记录BG的锋电位和场电位。MPTP中毒导致严重失眠，睡眠开始延迟、睡眠碎片化以及清醒时间增加。失眠伴随着非快速眼动（NREM）睡眠β振荡的出现，这些振荡在BG和大脑皮层中是同步的。BG的β振荡活动与整个皮层慢振荡（0.1 - 2赫兹）的减少相关，并且在自发觉醒之前BG的β活动和皮质 - BG的β相干性增加。最后，睡眠期间基底神经节中β振荡的增加与NREM睡眠减少、清醒增加以及更频繁的觉醒平行。这些结果确定了BG中NREM睡眠β振荡是PD失眠的神经关联，并提出了这种疾病可能出现的机制。
