Gale John T, Shields Donald C, Jain Felipe A, Amirnovin Ramin, Eskandar Emad N
Department of Neurosurgery, Harvard Medical School, Massachusetts General Hospital, 15 Parkman Street, ACC-021, Boston, MA 02114, USA.
Brain Res. 2009 Mar 13;1260:15-23. doi: 10.1016/j.brainres.2008.12.062. Epub 2009 Jan 7.
The pathophysiology of Parkinson disease (PD) is characterized by derangements in the discharge rates, bursting patterns, and oscillatory activity of basal ganglia (BG) neurons. In this study, subthalamic nucleus (STN) neuronal activity patterns in humans with PD were compared with that in the normal monkey during performance of similar volitional movements. Single-unit STN recordings were collected while PD patients and animals moved a joystick in the direction of targets presented on a monitor. When discharge rates in all PD human and normal monkey neurons were compared, no significant differences were observed. However, when neurons were classified by peri-movement response type (i.e., excited, inhibited, or unresponsive to movement) statistical differences were demonstrated - most significantly among PD excited neurons. Analysis of burst activity demonstrated inter- and intra-burst activities were greater in the PD human compared to the monkey irrespective of neuronal response type. Moreover, simultaneously recorded neurons in the human demonstrated consistent oscillatory synchronization at restricted frequency bands, whereas synchronized oscillatory neurons in the monkey were not restricted to distinct frequencies. During movement, discharge and burst rates were positively correlated, independent of subject or neuronal response type; however, rates and oscillatory activity were more strongly correlated in the PD human than the normal monkey. Interestingly, across all domains of analysis, STN neurons in PD demonstrated reduced response variability when compared to STN neurons in the normal monkey brain. Thus, the net effect of PD may be a reduction in the physiological degrees of freedom of BG neurons with diminished information carrying capacity.
帕金森病(PD)的病理生理学特征是基底神经节(BG)神经元的放电率、爆发模式和振荡活动紊乱。在本研究中,比较了PD患者与正常猴子在进行类似自主运动时丘脑底核(STN)神经元的活动模式。在PD患者和动物朝着监视器上呈现的目标方向移动操纵杆时,收集了STN的单神经元记录。比较所有PD患者和正常猴子神经元的放电率时,未观察到显著差异。然而,当根据运动周围反应类型(即对运动兴奋、抑制或无反应)对神经元进行分类时,显示出统计学差异——在PD兴奋神经元中最为显著。爆发活动分析表明,无论神经元反应类型如何,PD患者的爆发间和爆发内活动均比猴子更强。此外,在人类中同时记录的神经元在受限频段表现出一致的振荡同步,而猴子中的同步振荡神经元并不局限于特定频率。在运动过程中,放电率和爆发率呈正相关,与受试者或神经元反应类型无关;然而,PD患者的放电率和振荡活动之间的相关性比正常猴子更强。有趣的是,在所有分析领域中,与正常猴子大脑中的STN神经元相比,PD患者的STN神经元反应变异性降低。因此,PD的净效应可能是BG神经元生理自由度降低,信息承载能力减弱。