University of Utah Department of Neurology, Salt Lake City, UT, USA.
University of Utah Department of Biomedical Engineering, Salt Lake City, UT, USA; University of Utah Department of Neurosurgery, Salt Lake City, UT, USA; University of Utah Scientific Computing and Imaging Institute, Salt Lake City, UT, USA.
Brain Stimul. 2020 Jul-Aug;13(4):1040-1050. doi: 10.1016/j.brs.2020.03.017. Epub 2020 Apr 9.
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.
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.
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.
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.
实现深度脑刺激 (DBS) 剂量等效性具有挑战性，特别是在调节脉冲宽度和使用定向触点时。此外，脉冲宽度调节的确切效果尚不清楚，最近关于脉冲宽度调节对神经选择性影响的报告与经典生物物理研究相矛盾。
我们为两个轴突直径创建了多腔室神经元模型，并使用有限元建模来确定标准和分段电极的细胞外影响。我们分析了轴突激活轮廓并计算了激活的组织体积。
我们发现，长脉冲宽度将刺激效果集中在小而邻近的纤维上，抑制了远距离白质束的激活（这是 DBS 一些副作用的原因），并在维持小轴突等效激活时提高了电池利用率。定向导联可以在更大程度上实现类似的益处。重新审视以前关于短脉冲刺激减少副作用的报告，我们探讨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扩散减少。最后，我们以内囊回避为例，在丘脑下刺激的背景下，提出了一个患者特定的模型，展示了长脉冲宽度如何帮助增加生物物理治疗窗口。
我们与经典研究结果一致，并预测长脉冲宽度可能会将刺激效果集中在小而邻近的纤维上，并提高功耗。虽然未来关于脉冲宽度调节的临床前和临床研究是必要的，但很明显，未来的研究必须确保剂量等效性，注意到在改变脉冲宽度时，能量和电荷量等效的幅度不会导致神经激活的等效扩散。
