Increased beta-band oscillatory activity in the basal ganglia network is associated with Parkinsonian motor symptoms and is suppressed with medication and deep brain stimulation (DBS). The origins of the beta-band oscillations, however, remains unclear with both intrinsic oscillations arising within the subthalamic nucleus (STN)—external globus pallidus (GPe) network and exogenous beta-activity, originating outside the network, proposed as potential sources of the pathological activity. The aim of this study was to explore the relative contribution of autonomous oscillations and exogenous oscillatory inputs in the generation of pathological oscillatory activity in a biophysically detailed model of the parkinsonian STN-GPe network. The network model accounts for the integration of synaptic currents and their interaction with intrinsic membrane currents in dendritic structures within the STN and GPe. The model was used to investigate the development of beta-band synchrony and bursting within the STN-GPe network by changing the balance of excitation and inhibition in both nuclei, and by adding exogenous oscillatory inputs with varying phase relationships through the hyperdirect cortico-subthalamic and indirect striato-pallidal pathways. The model showed an intrinsic susceptibility to beta-band oscillations that was manifest in weak autonomously generated oscillations within the STN-GPe network and in selective amplification of exogenous beta-band synaptic inputs near the network's endogenous oscillation frequency. The frequency at which this resonance peak occurred was determined by the net level of excitatory drive to the network. Intrinsic or endogenously generated oscillations were too weak to support a pacemaker role for the STN-GPe network, however, they were considerably amplified by sparse cortical beta inputs and were further amplified by striatal beta inputs that promoted anti-phase firing of the cortex and GPe, resulting in maximum transient inhibition of STN neurons. The model elucidates a mechanism of cortical patterning of the STN-GPe network through feedback inhibition whereby intrinsic susceptibility to beta-band oscillations can lead to phase locked spiking under parkinsonian conditions. These results point to resonance of endogenous oscillations with exogenous patterning of the STN-GPe network as a mechanism of pathological synchronization, and a role for the pallido-striatal feedback loop in amplifying beta oscillations.

中文翻译：

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丘脑底核-苍白球网络生物物理详细模型中的 β 能带共振和固有振荡

基底神经节网络中β带振荡活动的增加与帕金森运动症状有关，并且可以通过药物和深部脑刺激（DBS）来抑制。然而，β 带振荡的起源仍不清楚，因为丘脑底核 (STN) 内产生的内在振荡 - 外部苍白球 (GPe) 网络和起源于网络外部的外源性 β 活性被认为是 β 频带振荡的潜在来源。病理活动。本研究的目的是探讨自主振荡和外源振荡输入在帕金森病 STN-GPe 网络的生物物理详细模型中产生病理振荡活动的相对贡献。该网络模型解释了突触电流的整合及其与 STN 和 GPe 内树突结构中固有膜电流的相互作用。该模型用于通过改变两个核中的兴奋和抑制平衡，并通过超直接皮质-底丘脑和超直接皮质-底丘脑添加具有不同相位关系的外源振荡输入来研究 STN-GPe 网络内 β 带同步和爆发的发展。间接纹状体-苍白球通路。该模型显示出对 β 波段振荡的内在敏感性，这表现在 STN-GPe 网络内自主生成的微弱振荡以及网络内源振荡频率附近的外源 β 波段突触输入的选择性放大中。该共振峰值出现的频率由网络兴奋驱动的净水平决定。内在或内源性产生的振荡太弱，无法支持 STN-GPe 网络的起搏器作用，然而，它们被稀疏的皮质 β 输入大大放大，并被促进皮质和 GPe 反相发射的纹状体 β 输入进一步放大，导致 STN 神经元的最大瞬时抑制。该模型通过反馈抑制阐明了 STN-GPe 网络的皮质模式机制，从而对 β 带振荡的内在敏感性可导致帕金森病条件下的锁相尖峰。这些结果表明，内源性振荡与 STN-GPe 网络的外源性模式共振是一种病理同步机制，也是苍白球-纹状体反馈环路在放大 β 振荡中的作用。