Ozturk Musa, Kaku Heet, Jimenez-Shahed Joohi, Viswanathan Ashwin, Sheth Sameer A, Kumar Suneel, Ince Nuri F
Department of Biomedical Engineering, University of Houston, Houston, TX, United States.
Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Front Neurosci. 2020 Apr 24;14:391. doi: 10.3389/fnins.2020.00391. eCollection 2020.
Single cell neuronal activity (SUA) and local field potentials (LFP) in the subthalamic nucleus (STN) of unmedicated Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS) surgery have been well-characterized during microelectrode recordings (MER). However, there is limited knowledge about the changes in the firing patterns and oscillations above and within the territories of STN after the intake of dopaminergic medication. Here, for the first time, we report the STN single cell and oscillatory neural dynamics in a medicated patient with idiopathic PD using intraoperative MER. We recorded LFP and SUA with microelectrodes at various depths during bilateral STN-DBS electrode implantation. We isolated 26 neurons in total and observed that tonic and irregular firing patterns of individual neurons predominated throughout the territories of STN. While burst-type firings have been well-characterized in the dorsal territories of STN in unmedicated patients, interestingly, this activity was not observed in our medicated subject. LFP recordings lacked the excessive beta (8-30 Hz) activity, characteristic of the unmedicated state and signal energy was mainly dominated by slow oscillations below 8 Hz. We observed sharp gamma oscillations between 70 and 90 Hz within and above the STN. Despite the presence of a broadband high frequency activity in 200-400 Hz range, no cross-frequency interaction in the form of phase-amplitude coupling was noted between low and high frequency oscillations of LFPs. While our results are in agreement with the previously reported LFP recordings from the DBS lead in medicated PD patients, the sharp gamma peak present throughout the depth recordings and the lack of bursting firings after levodopa intake have not been reported before. The lack of bursting in SUA, the lack of excessive beta activity and cross frequency coupling between HFOs and lower rhythms further validate the link between bursting firing regime of neurons and pathological oscillatory neural activity in PD-STN. Overall, these observations not only validate the existing literature on the PD electrophysiology in healthy/medicated animal models but also provide insights regarding the underlying electro-pathophysiology of levodopa-induced dyskinesias in PD patients through demonstration of multiscale relationships between single cell firings and field potentials.
在接受深部脑刺激（DBS）手术的未服药帕金森病（PD）患者的丘脑底核（STN）中，单细胞神经元活动（SUA）和局部场电位（LFP）在微电极记录（MER）期间已得到充分表征。然而，关于摄入多巴胺能药物后STN区域上方和内部的放电模式和振荡变化的了解有限。在此，我们首次报告了一名特发性PD服药患者术中MER记录的STN单细胞和振荡神经动力学。在双侧STN-DBS电极植入期间，我们使用微电极在不同深度记录LFP和SUA。我们总共分离出26个神经元，并观察到单个神经元的强直和不规则放电模式在STN区域中占主导地位。虽然在未服药患者的STN背侧区域爆发式放电已得到充分表征，但有趣的是，在我们的服药受试者中未观察到这种活动。LFP记录缺乏未服药状态特有的过度β（8 - 30 Hz）活动，信号能量主要由低于8 Hz的慢振荡主导。我们在STN内部和上方观察到70至90 Hz的尖锐γ振荡。尽管在200 - 400 Hz范围内存在宽带高频活动，但未发现LFP的低频和高频振荡之间存在相位 - 幅度耦合形式的交叉频率相互作用。虽然我们的结果与先前报道的服药PD患者DBS电极的LFP记录一致，但在整个深度记录中出现的尖锐γ峰值以及左旋多巴摄入后缺乏爆发式放电此前尚未见报道。SUA中缺乏爆发式放电、缺乏过度β活动以及高频振荡与较低节律之间缺乏交叉频率耦合，进一步证实了PD - STN中神经元爆发式放电模式与病理性振荡神经活动之间的联系。总体而言，这些观察结果不仅验证了健康/服药动物模型中关于PD电生理学的现有文献，还通过展示单细胞放电与场电位之间的多尺度关系，为PD患者左旋多巴诱导的运动障碍的潜在电病理生理学提供了见解。
