The cortico-basal ganglia circuit is needed to suppress prepotent actions and to facilitate controlled behavior. Under conditions of response conflict, the frontal cortex and subthalamic nucleus (STN) exhibit increased spiking and theta band power, which are linked to adaptive regulation of behavioral output. The electrophysiological mechanisms underlying these neural signatures of impulse control remain poorly understood. To address this lacuna, we constructed a novel large-scale, biophysically principled model of the subthalamopallidal (STN-globus pallidus externus) network and examined the mechanisms that modulate theta power and spiking in response to cortical input. Simulations confirmed that theta power does not emerge from intrinsic network dynamics but is robustly elicited in response to cortical input as burst events representing action selection dynamics. Rhythmic burst events of multiple cortical populations, representing a state of conflict where cortical motor plans vacillate in the theta range, led to prolonged STN theta and increased spiking, consistent with empirical literature. Notably, theta band signaling required NMDA, but not AMPA, currents, which were in turn related to a triphasic STN response characterized by spiking, silence, and bursting periods. Finally, theta band resonance was also strongly modulated by architectural connectivity, with maximal theta arising when multiple cortical populations project to individual STN "conflict detector" units because of an NMDA-dependent supralinear response. Our results provide insights into the biophysical principles and architectural constraints that give rise to STN dynamics during response conflict, and how their disruption can lead to impulsivity and compulsivity.

SIGNIFICANCE STATEMENT The subthalamic nucleus exhibits theta band power modulation related to cognitive control over motor actions during conditions of response conflict. However, the mechanisms of such dynamics are not understood. Here we developed a novel biophysically detailed and data-constrained large-scale model of the subthalamopallidal network, and examined the impacts of cellular and network architectural properties that give rise to theta dynamics. Our investigations implicate an important role for NMDA receptors and cortico-subthalamic nucleus topographical connectivities in theta power modulation.

需要皮质基底神经节回路来抑制优势行为并促进受控行为。在反应冲突的情况下，额叶皮层和底丘脑核（STN）表现出增加的尖峰和θ带功率，这与行为输出的适应性调节有关。这些冲动控制神经特征背后的电生理机制仍然知之甚少。为了解决这个缺陷，我们构建了一个新型的大规模、生物物理学原理的丘脑下苍白球（STN-globus pallidus externus）网络模型，并检查了响应皮层输入调节 theta 功率和尖峰的机制。模拟证实，theta 功率并不是从内在的网络动态中产生的，而是响应于代表动作选择动态的突发事件的皮质输入而被稳健地引出。多个皮质群的节律爆发事件代表了皮质运动计划在 θ 范围内摇摆的冲突状态，导致 STN θ 延长和尖峰增加，这与实证文献一致。值得注意的是，theta 波段信号需要 NMDA 电流，而不是 AMPA 电流，这反过来又与以尖峰、沉默和突发周期为特征的三相 STN 响应相关。最后，theta 带共振也受到结构连通性的强烈调节，当多个皮质群由于依赖于 NMDA 的超线性响应而投射到单个 STN“冲突检测器”单元时，会产生最大 theta。我们的研究结果提供了对在响应冲突期间引起 STN 动态的生物物理原理和架构约束的见解，以及它们的破坏如何导致冲动和强迫性。

意义陈述丘脑底核表现出与反应冲突条件下对运动动作的认知控制相关的 θ 带功率调制。然而，这种动力学的机制尚不清楚。在这里，我们开发了一种新颖的生物物理细节和数据受限的下丘脑苍白球网络的大规模模型，并检查了引起 theta 动力学的细胞和网络结构特性的影响。我们的研究表明 NMDA 受体和皮质底丘脑核拓扑连接在 θ 功率调节中发挥重要作用。