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基于模型的几何优化及空间选择性迷走神经刺激多电极袖带的体内验证。

Model-based geometrical optimisation and in vivo validation of a spatially selective multielectrode cuff array for vagus nerve neuromodulation.

机构信息

Medical Physics and Biomedical Engineering, University College London, UK.

Neuromodulation, Galvani Bioelectronics, Stevenage, UK.

出版信息

J Neurosci Methods. 2021 Mar 15;352:109079. doi: 10.1016/j.jneumeth.2021.109079. Epub 2021 Jan 28.

Abstract

BACKGROUND

Neuromodulation by electrical stimulation of the human cervical vagus nerve may be limited by adverse side effects due to stimulation of off-target organs. It may be possible to overcome this by spatially selective stimulation of peripheral nerves. Preliminary studies have shown this is possible using a cylindrical multielectrode human-sized nerve cuff in vagus nerve selective neuromodulation.

NEW METHOD

The model-based optimisation method for multi-electrode geometric design is presented. The method was applied for vagus nerve cuff array and suggested two rings of 14 electrodes, 3 mm apart, with 0.4 mm electrode width and separation and length 0.5-3 mm, with stimulation through a pair in the same radial position on the two rings. The electrodes were fabricated using PDMS-embedded stainless steel foil and PEDOT: pTS coating.

RESULTS

In the cervical vagus nerve in anaesthetised sheep, it was possible to selectively reduce the respiratory breath rate (RBR) by 85 ± 5% without affecting heart rate, or selectively reduce heart rate (HR) by 20 ± 7% without affecting respiratory rate. The cardiac- and pulmonary-specific sites on the nerve cross-sectional perimeter were localised with a radial separation of 105 ± 5 degrees (P < 0.01, N = 24 in 12 sheep).

CONCLUSIONS

Results suggest organotopic or function-specific organisation of neural fibres in the cervical vagus nerve. The optimised electrode array demonstrated selective electrical neuromodulation without adverse side effects. It may be possible to translate this to improved treatment by electrical autonomic neuromodulation for currently intractable conditions.

摘要

背景

通过刺激人体颈迷走神经的电刺激进行神经调节可能会由于对非靶器官的刺激而产生不良反应,从而受到限制。通过对周围神经的空间选择性刺激,可能可以克服这一问题。初步研究表明,使用圆柱状多电极人体大小的神经袖套在迷走神经选择性神经调节中可以实现这一点。

新方法

提出了基于模型的多电极几何设计优化方法。该方法应用于迷走神经袖套阵列,并提出了两个间隔 3mm 的 14 电极环,电极宽度和间隔为 0.4mm,长度为 0.5-3mm,通过同一两个环上的径向位置的一对电极进行刺激。电极使用 PDMS 嵌入的不锈钢箔和 PEDOT:pTS 涂层制造。

结果

在麻醉绵羊的颈迷走神经中,通过选择性地将呼吸率(RBR)降低 85%±5%而不影响心率,或者选择性地将心率(HR)降低 20%±7%而不影响呼吸率,是有可能的。神经横截面周长上的心脏和肺特异性部位的径向分离为 105°±5°(P<0.01,12 只羊中的 24 个 N)。

结论

结果表明,在颈迷走神经中存在神经纤维的器官特异性或功能特异性组织。优化后的电极阵列证明了选择性电神经调节而没有不良反应。通过对自主神经的电调节来改善目前难以治疗的疾病,这可能是可行的。

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