BACKGROUND Achieving deep brain stimulation (DBS) dose equivalence is challenging, especially with pulse width tuning and directional contacts. Further, the precise effects of pulse width tuning are unknown, and recent reports of the effects of pulse width tuning on neural selectivity are at odds with classic biophysical studies. METHODS We created multicompartment neuron models for two axon diameters and used finite element modeling to determine extracellular influence from standard and segmented electrodes. We analyzed axon activation profiles and calculated volumes of tissue activated. RESULTS We find that long pulse widths focus the stimulation effect on small, nearby fibers, suppressing distant white matter tract activation (responsible for some DBS side effects) and improving battery utilization when equivalent activation is maintained for small axons. Directional leads enable similar benefits to a greater degree. Reexamining previous reports of short pulse stimulation reducing side effects, we explore a possible alternate explanation: non-dose equivalent stimulation may have resulted in reduced spread of neural activation. Finally, using internal capsule avoidance as an example in the context of subthalamic stimulation, we present a patient-specific model to show how long pulse widths could help increase the biophysical therapeutic window. INTERPRETATIONS We find agreement with classic studies and predict that long pulse widths may focus the stimulation effect on small, nearby fibers and improve power consumption. While future pre-clinical and clinical work is necessary regarding pulse width tuning, it is clear that future studies must ensure dose equivalence, noting that energy- and charge-equivalent amplitudes do not result in equivalent spread of neural activation when changing pulse width.

中文翻译：

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通过脉冲宽度调谐和分段电极在深部脑刺激中的神经选择性、效率和剂量等效性

背景实现深部脑刺激（DBS）剂量等效具有挑战性，尤其是在脉冲宽度调谐和定向接触的情况下。此外，脉宽调节的精确效果尚不清楚，最近关于脉宽调节对神经选择性影响的报道与经典的生物物理学研究不一致。方法我们为两个轴突直径创建了多室神经元模型，并使用有限元建模来确定标准电极和分段电极对细胞外的影响。我们分析了轴突激活谱并计算了激活的组织体积。结果我们发现长脉冲宽度将刺激效应集中在附近的小纤维上，抑制远处白质束激活（负责一些 DBS 副作用）并在小轴突保持等效激活时提高电池利用率。定向线索在更大程度上实现了类似的好处。重新检查以前关于短脉冲刺激减少副作用的报告，我们探索了一种可能的替代解释：非剂量等效刺激可能导致神经激活的传播减少。最后，在丘脑底刺激的背景下，以内囊回避为例，我们提出了一个患者特定的模型，以展示多长的脉冲宽度可以帮助增加生物物理治疗窗口。解释我们发现与经典研究一致，并预测长脉冲宽度可能会将刺激效果集中在附近的小纤维上并提高功耗。