OBJECTIVE Direct activation of the hyperdirect (HD) pathway has been linked to therapeutic benefit from subthalamic deep brain stimulation (DBS) for the treatment of Parkinson's disease (PD). We sought to quantify the axonal conduction biophysics of corticofugal axons directly stimulated by subthalamic DBS and reconcile those findings with short-latency cortical evoked potential (EP) results. METHODS We used a detailed computational model of human subthalamic DBS to quantify axonal activation and conduction. Signal propagation to cortex was evaluated for medium (5.7 µm), large (10.0 µm), and exceptionally large (15.0 µm) diameter corticofugal axons associated with either internal capsule (IC) fibers of passage or the HD pathway. We then compared the modeling results to human cortical EP measurements that have described an exceptionally fast component (EP0) occurring ~1 ms after the stimulus pulse, a fast component (EP1) at ~3 ms, and a slower component (EP2) at ~5 ms. RESULTS Subthalamic stimulation of the HD pathway with large and medium diameter axons propagated action potentials to cortex with timings that coincide with the EP1 and EP2 signals, respectively. Only direct activation of exceptionally large diameter fibers in the IC generated signals that could approach the EP0 timing. However, the action potential biophysics do not generally support the existence of a cortical EP less than 1.5 ms after DBS onset. CONCLUSIONS The EP1 and EP2 signals can be biophysically linked to antidromic activation of the HD pathway. SIGNIFICANCE Theoretical reconstruction of cortical EPs from subthalamic DBS demonstrate a convergence of anatomical, biophysical, and electrophysiological results.

中文翻译：

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下丘脑深部脑刺激产生的短延迟皮层诱发电位下信号传导的生物物理重建

目标超直接 (HD) 通路的直接激活与丘脑深部脑刺激 (DBS) 治疗帕金森病 (PD) 的治疗益处有关。我们试图量化由丘脑下 DBS 直接刺激的 corticofugal 轴突的轴突传导生物物理学，并将这些发现与短潜伏期皮质诱发电位 (EP) 结果相协调。方法 我们使用人类丘脑底 DBS 的详细计算模型来量化轴突激活和传导。针对与内囊 (IC) 通道或 HD 通路相关的中等 (5.7 µm)、大 (10.0 µm) 和异常大 (15.0 µm) 直径的皮质轴突评估信号传播到皮层。然后，我们将建模结果与人类皮层 EP 测量结果进行了比较，这些测量结果描述了在刺激脉冲后约 1 ms 发生的异常快速分量 (EP0)、在约 3 ms 发生的快速分量 (EP1) 和在~时发生的较慢分量 (EP2)。 5 毫秒。结果 大中径轴突对 HD 通路的下丘脑刺激将动作电位传播到皮层，其时间分别与 EP1 和 EP2 信号一致。只有直接激活 IC 中的超大直径光纤才能生成接近 EP0 时序的信号。然而，动作电位生物物理学通常不支持在 DBS 发作后小于 1.5 ms 的皮质 EP 的存在。结论 EP1 和 EP2 信号在生物物理上与 HD 通路的逆向激活有关。