Gale John T, Amirnovin Ramin, Williams Ziv M, Flaherty Alice W, Eskandar Emad N
Department of Neurosurgery, Massachusetts General Hospital, Boston, MA 02114, USA.
Neurosci Biobehav Rev. 2008;32(3):378-87. doi: 10.1016/j.neubiorev.2006.11.005. Epub 2007 Apr 26.
Despite remarkable advances, the relationship between abnormal neuronal activity and the clinical manifestations of Parkinson disease (PD) remains unclear. Numerous hypotheses have emerged to explain the relationship between neuronal activity and symptoms such as tremor, rigidity and akinesia. Among these are the antagonist balance hypothesis wherein increased firing rates in the indirect pathway inhibits movement; the selectivity hypothesis wherein loss of neuronal selectivity leads to an inability to select or initiate movements; the firing pattern hypothesis wherein increased oscillation and synchronization contribute to tremor and disrupt information flow; and the learning hypothesis, wherein the basal ganglia are conceived as playing an important role in learning sensory-motor associations which is disrupted by the loss of dopamine. Deep brain stimulation (DBS) surgery provides a unique opportunity to assess these different ideas since neuronal activity can be directly recorded from PD patients. The emerging data suggest that the pathophysiologic changes include derangements in the overall firing rates, decreased neuronal selectivity, and increased neuronal oscillation and synchronization. Thus, elements of all hypotheses are present, emphasizing that the loss of dopamine results in a profound and multifaceted disruption of normal information flow through the basal ganglia that ultimately leads to the signs and symptoms of PD.
尽管取得了显著进展，但异常神经元活动与帕金森病（PD）临床表现之间的关系仍不明确。已经出现了许多假说来解释神经元活动与震颤、僵硬和运动迟缓等症状之间的关系。其中包括拮抗剂平衡假说，即间接通路中放电频率增加会抑制运动；选择性假说，即神经元选择性丧失导致无法选择或启动运动；放电模式假说，即振荡和同步性增加导致震颤并扰乱信息流；以及学习假说，即基底神经节在学习感觉运动关联中起重要作用，而多巴胺丧失会破坏这种关联。深部脑刺激（DBS）手术提供了一个独特的机会来评估这些不同的观点，因为可以直接记录PD患者的神经元活动。新出现的数据表明，病理生理变化包括整体放电频率紊乱、神经元选择性降低以及神经元振荡和同步性增加。因此，所有假说的要素都存在，这强调多巴胺丧失会导致通过基底神经节的正常信息流受到深刻而多方面的破坏，最终导致PD的体征和症状。
