丘脑底核神经元放电频率和振荡活动与帕金森病进展的关系

Neuronal firing rate and oscillatory activity in subthalamic nucleus associated with Parkinson＇s disease progression

目的探讨帕金森病（PD）患者丘脑底核（STN）神经元放电频率和振荡活动与运动症状进展的关系。方法回顾性分析2015年3月至2016年3月首都医科大学宣武医院北京功能神经外科研究所采用STN刺激术治疗的PD患者，共22例。依据发病时间、起病侧及术前“关”状态下PD综合评分量表中的运动评分，将患者分为轻症组（11侧STN）和重症组（21侧STN）。术中应用微电极记录技术采集细胞电活动，单细胞和峰间隔分析鉴别细胞放电频率和模式，功率谱分析神经元振荡活动的特点。结果32个STN针道中共记录到163个神经元的电生理信号，其中轻症组66个，重症组97个。轻症组和重症组的平均放电频率分别为（46．2±13．6）Hz和（59．9±17．1）Hz，差异有统计学意义（P〈0．01）；轻症组STN振荡活动神经元所占比例为40．9％（27／66），低于重症组的56．7％（55／97）；B频谱振荡活动神经元所占比例为29．7％（8／27），低于重症组的52．7％（29／55），差异均有统计学意义（均P〈0．01）。与轻症组相比，重症组平均放电频率增加29．6％，振荡活动神经元所占比例增加38．6％，其中13FB振荡活动神经元所占比例增加77．8％。结论STN神经元放电频率和振荡活动神经元比例的增加，特别是BFB振荡活动神经元比例的增加与PD运动症状进展有关。

Objective To explore whether neuronal firing rate and proportion of oscillatory neuronal activity in subthalamic nucleus （STN） is associated with Parkinson＇s disease （PD） progression. Methods Twenty-two patients with PD treated with STN deep brain stimulation （DBS） at Beijing Institute of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University from March 2015 to March 2016 were analyzed retrospectively. Microelectrode recording was performed in the STN. Single unit analysis including interspike interval （ISI） was used to study neuronal firing rate and patterns. Power spectral analysis was used to evaluate neuronal oscillation. Clinical outcome was assessed using Unified Parkinson~ Disease Rating Scales （UPDRS III） pre-and post-surgery. The groups of the early stage and the advanced-stage were defined based on the UPDRS III scores, disease duration and the side of initial symptoms. Results Of total 163 neurons identified from 32 STN, there were 66 neurons with mean firing rate of 46.2 _＋ 13.6 Hz obtained from the patients in the early-stage group whereas 97 neurons with mean firing rate of 59. 9 _＋ 17.1 Hz were obtained from patients in the advanced-stage group. Power spectral analysis showed that there were 27 （40.9%） oscillatory neurons identified from the STN neurons in the early-stage patient group （n = 66） whereas 55 （56.7%） oscillatory neurons were identified from the STN neurons in the advanced-stage patient group （n = 95 ）. Further analysis found that 29.7% （8/27） 13 oscillatory neurons were observed in the early stage group whereas 52.7% （ 29/55 ） 13 oscillatory neurons were observed in the advanced stage group. When comparing the mean firing rate and proportion of oscillatory neurons in the STN of early-stage group with that of neurons in the STN of advanced-stage group, it was found that there was a 29. 6% increase STN mean firing rate of neurons （46.2 ±13.6 Hz vs. 59.9±17.1 Hz, P 〈 0.05 ） and a 36.8% increase proportion of oscillatory neurons （40.9% vs. 56.7% ） between the two groups. In particular, a 77.8% increase proportion of β oscillatory neurons was obtained between the early-stage and advanced-stage groups （29.7% vs. 52.8% ,P 〈 0.01 ）. Conclusion The results strongly suggest that both subthalamic nucleus neuronal firing rate and proportion of 13 oscillatory neurons increase with PD progression.