Enhanced transcutaneous electrical nerve stimulation achieved by a localized virtual bipole: A computational study of human tibial nerve stimulation.
- 作者列表："Roointan S","Tovbis D","Elder C","Yoo PB
OBJECTIVE:Electrical neuromodulation is a clinically effective therapeutic instrument, currently expanding into newer indications and larger patient populations. Neuromodulation technologies are also moving towards less invasive approaches to nerve stimulation. In this study, we investigated an enhanced transcutaneous electrical nerve stimulation (eTENS) system that electrically couples a conductive nerve cuff with a conventional TENS electrode. The objectives were to better understand how eTENS achieves lower nerve activation thresholds, and to test the feasibility of applying eTENS in a human model of peripheral nerve stimulation. APPROACH:A finite element model (FEM) of the human lower leg was constructed to simulate electrical stimulation of the tibial nerve, comparing TENS and eTENS. Key variables included surface electrode diameter, nerve cuff properties (conductivity, length, thickness), and cuff location. Enhanced neural excitability was predicted by relative excitability (RE > 1), derived using either the activating function (AF) or the nerve activation threshold (MRG model). MAIN RESULTS:Simulations revealed that a localized 'virtual bipole' was created on the target nerve, where the isopotential surface of the cuff resulted in large potential differences with the surrounding tissue. The cathodic part (nerve depolarization) of the bipole enhanced neural excitability, predicted by RE values of up to 2.2 (MRG) and 5.5 (AF) when compared to TENS. The MRG model confirmed that action potentials were initiated at the cathodic edge of the nerve cuff. Factors contributing to eTENS were larger surface electrodes, longer cuffs, cuff conductivity (> 1*103 S/m), and cuff position relative to the cathodic surface electrode. SIGNIFICANCE:This study provides a theoretical basis for designing and testing eTENS applied to various neural targets and data suggesting function of eTENS in large models of nerve stimulation. Although eTENS carries key advantages over existing technologies, further work is needed to translate this approach into effective clinical therapy.
目的: 电神经调节是一种临床有效的治疗仪器，目前正在扩展到新的适应症和更大的患者人群。神经调节技术也在朝着神经刺激的微创方法发展。在这项研究中，我们研究了一种增强型经皮电神经刺激 (eTENS) 系统，它将导电神经袖带与传统的 TENS 电极电耦合。目的是更好地理解 eTENS 如何达到较低的神经激活阈值，并测试在周围神经刺激的人体模型中应用 eTENS 的可行性。 方法: 构建人体小腿有限元模型 (FEM)，模拟电刺激胫神经，比较 TENS 和 eTENS。关键变量包括表面电极直径、神经套囊特性 (电导率、长度、厚度) 和套囊位置。通过相对兴奋性 (RE > 1) 预测增强的神经兴奋性，使用激活功能 (AF) 或神经激活阈值 (MRG 模型) 推导。 主要结果: 模拟显示，在目标神经上创建了一个局部的 “虚拟双极”，其中袖带的等电位表面与周围组织产生了较大的电位差。Bipole 的阴极部分 (神经去极化) 增强了神经兴奋性，与 TENS 相比，通过高达 2.2 (MRG) 和 5.5 (AF) 的 RE 值预测。MRG 模型证实动作电位启动于神经套囊的阴极边缘。影响 eTENS 的因素是较大的表面电极、较长的袖口、袖口电导率 (> 1*103 S/m) 和袖口相对于阴极表面电极的位置。 意义: 本研究为设计和测试应用于各种神经靶点的 eTENS 以及在神经刺激的大型模型中提示 eTENS 功能的数据提供了理论基础。虽然 eTENS 与现有技术相比具有关键优势，但需要进一步的工作将这种方法转化为有效的临床治疗。
METHODS::In recent years, transcranial electrical stimulation (tES) has been used to improve cognitive and perceptual abilities and to boost learning. In the visual domain, transcranial random noise stimulation (tRNS), a type of tES in which electric current is randomly alternating in between two electrodes at high frequency, has shown potential in inducing long lasting perceptual improvements when coupled with tasks such as contrast detection. However, its cortical mechanisms and online effects have not been fully understood yet, and it is still unclear whether these long-term improvements are due to early-stage perceptual enhancements of contrast sensitivity or later stage mechanisms such as learning consolidation. Here we tested tRNS effects on multiple spatial frequencies and orientation, showing that tRNS enhances detection of a low contrast Gabor, but only for oblique orientation and high spatial frequency (12 cycles per degree of visual angle). No improvement was observed for low contrast and vertical stimuli. These results indicate that tRNS can enhance contrast sensitivity already after one training session, however this early onset is dependent on characteristics of the stimulus such as spatial frequency and orientation. In particular, the shallow depth of tRNS is likely to affect superficial layers of the visual cortex where neurons have higher preferred spatial frequencies than cells in further layers, while the lack of effect on vertical stimuli might reflect the optimization of the visual system to see cardinally oriented low contrast stimuli, leaving little room for short-term improvement. Taken together, these results suggest that online tRNS effects on visual perception are the result of a complex interaction between stimulus intensity and cortical anatomy, consistent with previous literature on brain stimulation.
METHODS:OBJECTIVE:There is growing interest in treating diseases by electrical stimulation and block of peripheral autonomic nerves, but a paucity of studies on excitation and block of small diameter autonomic axons. We conducted in vivo quantification of the strength-duration properties, activity-dependent slowing (ADS), and responses to kilohertz frequency (KHF) signals for the rat vagus nerve (VN). APPROACH:We conducted acute in vivo experiments in urethane-anesthetised rats. We placed two cuff electrodes on the left cervical VN and one cuff electrode on the anterior subdiaphragmatic VN. The rostral cervical cuff was used to deliver pulses to quantify recruitment and ADS. The caudal cervical cuff was used to deliver KHF signals. The subdiaphragmatic cuff was used to record compound action potentials (CAPs). MAIN RESULTS:We quantified the input-output recruitment and strength-duration curves. Fits to the data using standard strength-duration equations were qualitatively similar, but the resulting chronaxie and rheobase estimates varied substantially. We measured larger thresholds for the slowest fibres (0.5 to 1 m/s), especially at shorter pulse widths. Using a novel cross-correlation CAP-based analysis, we measured ADS of ~2.3% after 3 min of 2 Hz stimulation, which is comparable to ADS reported for sympathetic efferents in somatic nerves, but much smaller than ADS in cutaneous nociceptors. We found greater ADS with higher stimulation frequency and non-monotonic changes in CV in select cases. We found monotonically increasing block thresholds across frequencies from 10 to 80 kHz for both fast and slow fibres. Further, following 25 s of KHF signal, neural conduction could require tens of seconds to recover. SIGNIFICANCE:The quantification of mammalian autonomic nerve responses to conventional and KHF signals provides essential information for development of peripheral nerve stimulation therapies and for understanding their mechanisms of action.
METHODS:BACKGROUND:Early accounts of forced thought were reported at the onset of a focal seizure, and characterized as vague, repetitive, and involuntary intellectual auras distinct from perceptual or psychic hallucinations or illusions. Here, we examine the neural underpinnings involved in conceptual thought by presenting a series of 3 patients with epilepsy reporting intrusive thoughts during electrical stimulation of the left lateral prefrontal cortex (PFC) during invasive surgical evaluation. We illustrate the widespread networks involved through two independent brain imaging modalities: resting state functional magnetic resonance imaging (fMRI) (rs-fMRI) and task-based meta-analytic connectivity modeling (MACM). METHODS:We report the clinical and stimulation characteristics of three patients with left hemispheric language dominance who demonstrate forced thought with functional mapping. To examine the brain networks underlying this phenomenon, we used the regions of interest (ROI) centered at the active electrode pairs. We modeled functional networks using two approaches: (1) rs-fMRI functional connectivity analysis, representing 81 healthy controls and (2) meta-analytic connectivity modeling (MACM), representing 8260 healthy subjects. We also determined the overlapping regions between these three subjects' rs-fMRI and MACM networks through a conjunction analysis. RESULTS:We identified that left PFC was associated with a large-scale functional network including frontal, temporal, and parietal regions, a network that has been associated with multiple cognitive functions including semantics, speech, attention, working memory, and explicit memory. CONCLUSIONS:We illustrate the neural networks involved in conceptual thought through a unique patient population and argue that PFC supports this function through activation of a widespread network.