Department of Biomedical Engineering, Washington University, St. Louis, MO 63130, United States of America.
J Neural Eng. 2018 Apr;15(2):026009. doi: 10.1088/1741-2552/aa9e96.
Regenerated peripheral nervous tissue possesses different morphometric properties compared to undisrupted nerve. It is poorly understood how these morphometric differences alter the response of the regenerated nerve to electrical stimulation. In this work, we use computational modeling to explore the electrophysiological response of regenerated and undisrupted nerve axons to electrical stimulation delivered by macro-sieve electrodes (MSEs).
A 3D finite element model of a peripheral nerve segment populated with mammalian myelinated axons and implanted with a macro-sieve electrode has been developed. Fiber diameters and morphometric characteristics representative of undisrupted or regenerated peripheral nervous tissue were assigned to core conductor models to simulate the two tissue types. Simulations were carried out to quantify differences in thresholds and chronaxie between undisrupted and regenerated fiber populations. The model was also used to determine the influence of axonal caliber on recruitment thresholds for the two tissue types. Model accuracy was assessed through comparisons with in vivo recruitment data from chronically implanted MSEs.
Recruitment thresholds of individual regenerated fibers with diameters >2 µm were found to be lower compared to same caliber undisrupted fibers at electrode to fiber distances of less than about 90-140 µm but roughly equal or higher for larger distances. Caliber redistributions observed in regenerated nerve resulted in an overall increase in average recruitment thresholds and chronaxie during whole nerve stimulation. Modeling results also suggest that large diameter undisrupted fibers located close to a longitudinally restricted current source such as the MSE have higher average recruitment thresholds compared to small diameter fibers. In contrast, large diameter regenerated nerve fibers located in close proximity of MSE sites have, on average, lower recruitment thresholds compared to small fibers. Utilizing regenerated fiber morphometry and caliber distributions resulted in accurate predictions of in vivo recruitment data.
Our work uses computational modeling to show how morphometric differences between regenerated and undisrupted tissue results in recruitment threshold discrepancies, quantifies these differences, and illustrates how large undisrupted nerve fibers close to longitudinally restricted current sources have higher recruitment thresholds compared to adjacently positioned smaller fibers while the opposite is true for large regenerated fibers.
再生周围神经组织与未受损神经相比具有不同的形态计量学特性。人们对这些形态计量学差异如何改变再生神经对电刺激的反应知之甚少。在这项工作中，我们使用计算建模来探索再生和未受损神经轴突对宏观筛电极（MSE）施加电刺激的电生理反应。
已经开发了一种带有哺乳动物髓鞘轴突的周围神经节段的 3D 有限元模型，并植入了宏观筛电极。将代表未受损或再生周围神经组织的纤维直径和形态计量学特征分配给芯线导体模型，以模拟两种组织类型。进行模拟以量化未受损和再生纤维群体之间阈值和时程差异。该模型还用于确定轴突口径对两种组织类型募集阈值的影响。通过与慢性植入 MSE 的体内募集数据进行比较来评估模型的准确性。
在电极到纤维距离小于约 90-140 µm 时，发现直径>2 µm 的个别再生纤维的募集阈值低于相同口径的未受损纤维，但在较大距离时大致相等或更高。再生神经中观察到的口径分布导致整个神经刺激时平均募集阈值和时程增加。建模结果还表明，与 MSE 等纵向受限电流源靠近的大直径未受损纤维具有比小直径纤维更高的平均募集阈值。相比之下，位于 MSE 附近的大直径再生神经纤维的平均募集阈值低于小纤维。利用再生纤维形态计量学和口径分布可以准确预测体内募集数据。
我们的工作使用计算建模来展示再生和未受损组织之间的形态计量学差异如何导致募集阈值差异，量化这些差异，并说明靠近纵向受限电流源的大直径未受损纤维与相邻定位的较小纤维相比具有较高的募集阈值，而对于大的再生纤维则相反。
