Modeling the response of small myelinated axons in a compound nerve to kilohertz frequency signals.
Modeling the response of small myelinated axons in a compound nerve to kilohertz frequency signals.
复制标题
DOI：
10.1088/1741-2552/aa6a5f
复制
发表时间：
2017-08
影响因子：
4
通讯作者：
Grill WM
中科院分区：
文献类型：
--
作者：
Pelot NA;Behrend CE;Grill WM
对周围神经，特别是自主神经的电神经调节以治疗各种疾病的兴趣越来越大。千赫频率（KHF）范围内的电信号可以产生不同的反应，包括传导阻滞。例如，用于肥胖症的EnteroMedics的vBloc®疗法提供5 kHz刺激以阻断腹部迷走神经，但作用机制尚不清楚。我们开发了一个两部分的计算模型，将人体腹部迷走神经周围的袖带电极的三维有限元模型与生物医学上真实的电路等效（电缆）模型轴突（直径为1，2和5.7 μm）耦合。我们开发了一种自动算法，将传导反应分类为阈下（传输）、KHF诱发活动（兴奋）或阻滞。我们量化了千赫兹频率（5至20 kHz），振幅（1至8 mA）和电极设计的神经反应。我们发现异质性的传导反应在整个建模的神经干，无论是对于一个给定的参数集和跨参数集，虽然大多数阈上反应的兴奋，而不是块。发射模式是不规则的传输和块边界附近，但其他规则，和平均发射率随电极纤维的距离。此外，我们确定了在振幅高于阻断阈值时的兴奋反应，称为“再兴奋”，由虚拟阴极处启动的动作电位引起。兴奋和块阈值下降，较小的电极纤维的距离，较大的纤维直径，和较低的千赫频率。一个点源模型预测了一个更大的部分阻塞的纤维和更大的变化阈值与距离相比，现实的袖口和神经模型。我们广泛的异步KHF诱发活动的研究结果表明，在腹部迷走神经传导阻滞是不可能与目前的临床参数。我们的研究结果表明，复合神经或下游肌肉力量的记录可能是不可靠的定量测量的神经活动的体内研究或作为生物标志物在闭环临床设备。
There is growing interest in electrical neuromodulation of peripheral nerves, particularly autonomic nerves, to treat various diseases. Electrical signals in the kilohertz frequency (KHF) range can produce different responses, including conduction block. For example, EnteroMedics’ vBloc® therapy for obesity delivers 5 kHz stimulation to block the abdominal vagus nerves, but the mechanisms of action are unclear. We developed a two-part computational model, coupling a three-dimensional finite element model of a cuff electrode around the human abdominal vagus nerve with biophysically-realistic electrical circuit equivalent (cable) model axons (1, 2, and 5.7 μm in diameter). We developed an automated algorithm to classify conduction responses as subthreshold (transmission), KHF-evoked activity (excitation), or block. We quantified neural responses across kilohertz frequencies (5 to 20 kHz), amplitudes (1 to 8 mA), and electrode designs. We found heterogeneous conduction responses across the modeled nerve trunk, both for a given parameter set and across parameter sets, although most suprathreshold responses were excitation, rather than block. The firing patterns were irregular near transmission and block boundaries, but otherwise regular, and mean firing rates varied with electrode-fibre distance. Further, we identified excitation responses at amplitudes above block threshold, termed “re-excitation”, arising from action potentials initiated at virtual cathodes. Excitation and block thresholds decreased with smaller electrode-fibre distances, larger fibre diameters, and lower kilohertz frequencies. A point source model predicted a larger fraction of blocked fibres and greater change of threshold with distance as compared to the realistic cuff and nerve model. Our findings of widespread asynchronous KHF-evoked activity suggest that conduction block in the abdominal vagus nerves is unlikely with current clinical parameters. Our results indicate that compound neural or downstream muscle force recordings may be unreliable as quantitative measures of neural activity for in vivo studies or as biomarkers in closed-loop clinical devices.
登录
查看更多内容
影响因子：
4
作者：
Ackermann DM;Bhadra N;Gerges M;Thomas PJ
通讯作者：
Thomas PJ
影响因子：
3.4
作者：
Bhadra, N;Kilgore, KL
通讯作者：
Kilgore, KL
影响因子：
2.5
作者：
Crosby, Nathan D.;Janik, John J.;Grill, Warren M.
通讯作者：
Grill, Warren M.
DOI：
10.1111/pme.12294
发表时间：
2014-03
期刊：
Pain medicine (Malden, Mass.)
影响因子：
--
作者：
Al-Kaisy A;Van Buyten JP;Smet I;Palmisani S;Pang D;Smith T
通讯作者：
Smith T
影响因子：
3.8
作者：
Camilleri, M.;Toouli, J.;Anvari, M.
通讯作者：
Anvari, M.