Marceglia S, Foffani G, Bianchi A M, Baselli G, Tamma F, Egidi M, Priori A
Dipartimento di Scienze Neurologiche, Università di Milano, Fondazione IRCCS Ospedale Maggiore Policlinico, Milano, Italy.
J Physiol. 2006 Mar 15;571(Pt 3):579-91. doi: 10.1113/jphysiol.2005.100271. Epub 2006 Jan 12.
The basic information architecture in the basal ganglia circuit is under debate. Whereas anatomical studies quantify extensive convergence/divergence patterns in the circuit, suggesting an information sharing scheme, neurophysiological studies report an absence of linear correlation between single neurones in normal animals, suggesting a segregated parallel processing scheme. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys and in parkinsonian patients single neurones become linearly correlated, thus leading to a loss of segregation between neurones. Here we propose a possible integrative solution to this debate, by extending the concept of functional segregation from the cellular level to the network level. To this end, we recorded local field potentials (LFPs) from electrodes implanted for deep brain stimulation (DBS) in the subthalamic nucleus (STN) of parkinsonian patients. By applying bispectral analysis, we found that in the absence of dopamine stimulation STN LFP rhythms became non-linearly correlated, thus leading to a loss of segregation between rhythms. Non-linear correlation was particularly consistent between the low-beta rhythm (13-20 Hz) and the high-beta rhythm (20-35 Hz). Levodopa administration significantly decreased these non-linear correlations, therefore increasing segregation between rhythms. These results suggest that the extensive convergence/divergence in the basal ganglia circuit is physiologically necessary to sustain LFP rhythms distributed in large ensembles of neurones, but is not sufficient to induce correlated firing between neurone pairs. Conversely, loss of dopamine generates pathological linear correlation between neurone pairs, alters the patterns within LFP rhythms, and induces non-linear correlation between LFP rhythms operating at different frequencies. The pathophysiology of information processing in the human basal ganglia therefore involves not only activities of individual rhythms, but also interactions between rhythms.
基底神经节回路中的基本信息架构仍存在争议。解剖学研究量化了该回路中广泛的汇聚/发散模式，提示存在一种信息共享机制；而神经生理学研究报告称，正常动物的单个神经元之间不存在线性相关性，提示存在一种分离的并行处理机制。在1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）处理的猴子和帕金森病患者中，单个神经元变得线性相关，从而导致神经元之间的分离丧失。在此，我们通过将功能分离的概念从细胞水平扩展到网络水平，提出了一个可能解决这一争议的综合方案。为此，我们记录了帕金森病患者丘脑底核（STN）中用于深部脑刺激（DBS）植入电极的局部场电位（LFP）。通过应用双谱分析，我们发现，在缺乏多巴胺刺激的情况下，STN的LFP节律变得非线性相关，从而导致节律之间的分离丧失。低β节律（13 - 20Hz）和高β节律（20 - 35Hz）之间的非线性相关性尤为一致。左旋多巴给药显著降低了这些非线性相关性，从而增加了节律之间的分离。这些结果表明，基底神经节回路中广泛的汇聚/发散在生理上对于维持分布在大量神经元集合中的LFP节律是必要的，但不足以诱导神经元对之间的相关放电。相反，多巴胺缺失会在神经元对之间产生病理性线性相关性，改变LFP节律内的模式，并在不同频率运行的LFP节律之间诱导非线性相关性。因此，人类基底神经节中信息处理的病理生理学不仅涉及单个节律的活动，还涉及节律之间的相互作用。
