Modelling the impact of altered axonal morphometry on the response of regenerative nervous tissue to electrical stimulation through macro-sieve electrodes

Zellmer, Erik R.; MacEwan, Matthew R.; Moran, Daniel W.

doi:10.1088/1741-2552/aa9e96

Cited by 10 publications

(12 citation statements)

References 81 publications

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“…This differential proliferation implies that the distance from a core channel to an average regenerated sensory axon should be less than from a peripheral channel. Previous simulations by our group (Zellmer et al, 2018) have predicted that regenerated axons' thresholds for activation are not inherently higher or lower than those of undisrupted axons, but rather depend on proximity to the stimulating lead. Effectively, thresholds for nearby regenerated axons should be lower than for naïve axons of the same caliber, while thresholds for regenerated axons that are farther away should be higher than for their naïve counterparts.…”

Section: Detection Thresholds For Single-channel Stimulus Configurationsmentioning

confidence: 79%

“…Prior simulation work by our group (Zellmer et al, 2018) suggests that recruitment thresholds for regenerated axons are not inherently higher or lower than for undisrupted axons, but depend on their distance from the stimulating lead and the manner of stimulation. Accordingly, Zellmer et al (2018) predict that regenerated axons located near the stimulating lead should have lower thresholds than undisrupted axons and that those further away should have higher thresholds. MacEwan et al (2016) demonstrated selective recruitment of distal musculature using single-channel stimuli from an MSE implanted in the rat sciatic nerve, indicating its potential use as a chronic implant for the restoration of motor control to a paralyzed limb.…”

Section: Introductionmentioning

confidence: 94%

“…Regenerated axons have thinner myelin sheaths, tend toward smaller calibers, and have shorter internodal separation than their undisrupted counterparts (Beuche and Friede, 1985;Friede and Beuche, 1985;Negredo et al, 2004;Castro et al, 2008), and so can be expected to differ in their electrophysiological response to stimulation by an implanted electrode interface (McNeal, 1976). Prior simulation work by our group (Zellmer et al, 2018) suggests that recruitment thresholds for regenerated axons are not inherently higher or lower than for undisrupted axons, but depend on their distance from the stimulating lead and the manner of stimulation. Accordingly, Zellmer et al (2018) predict that regenerated axons located near the stimulating lead should have lower thresholds than undisrupted axons and that those further away should have higher thresholds.…”

Section: Introductionmentioning

confidence: 99%

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Sensory Percepts Elicited by Chronic Macro-Sieve Electrode Stimulation of the Rat Sciatic Nerve

et al. 2021

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Objective: Intuitive control of conventional prostheses is hampered by their inability to provide the real-time tactile and proprioceptive feedback of natural sensory pathways. The macro-sieve electrode (MSE) is a candidate interface to amputees’ truncated peripheral nerves for introducing sensory feedback from external sensors to facilitate prosthetic control. Its unique geometry enables selective control of the complete nerve cross-section by current steering. Unlike previously studied interfaces that target intact nerve, the MSE’s implantation requires transection and subsequent regeneration of the target nerve. Therefore, a key determinant of the MSE’s suitability for this task is whether it can elicit sensory percepts at low current levels in the face of altered morphology and caliber distribution inherent to axon regeneration. The present in vivo study describes a combined rat sciatic nerve and behavioral model developed to answer this question.Approach: Rats learned a go/no-go detection task using auditory stimuli and then underwent surgery to implant the MSE in the sciatic nerve. After healing, they were trained with monopolar electrical stimuli with one multi-channel and eight single-channel stimulus configurations. Psychometric curves derived by the method of constant stimuli (MCS) were used to calculate 50% detection thresholds and associated psychometric slopes. Thresholds and slopes were calculated at two time points 3 weeks apart.Main Results: For the multi-channel stimulus configuration, the average current required for stimulus detection was 19.37 μA (3.87 nC) per channel. Single-channel thresholds for leads located near the nerve’s center were, on average, half those of leads located near the periphery (54.92 μA vs. 110.71 μA, or 10.98 nC vs. 22.14 nC). Longitudinally, 3 of 5 leads’ thresholds decreased or remained stable over the 3-week span. The remaining two leads’ thresholds increased by 70–74%, possibly due to scarring or device failure.Significance: This work represents an important first step in establishing the MSE’s viability as a sensory feedback interface. It further lays the groundwork for future experiments that will extend this model to the study of other devices, stimulus parameters, and task paradigms.

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Section: Detection Thresholds For Single-channel Stimulus Configurationsmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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Sensory Percepts Elicited by Chronic Macro-Sieve Electrode Stimulation of the Rat Sciatic Nerve

et al. 2021

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“…The higher threshold voltages may have multiple causes. First, newly regenerated nerve fibers crossing the MSEs’ transit zones would have smaller diameters and thinner myelin sheaths than their naïve counterparts [ 22 ]. Smaller diameter and unmyelinated fibers have previously been shown to require greater stimulation to achieve the block compared with myelinated fibers of larger diameter [ 23 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

High-Frequency Alternating Current Block Using Macro-Sieve Electrodes: A Pilot Study

Ray¹,

Javeed²,

Khalifeh³

et al. 2021

Cureus

Self Cite

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Background and objective High-frequency alternating current (HFAC) can yield a rapid-acting and reversible nerve conduction block. The present study aimed to demonstrate the successful implementation of HFAC block delivery via regenerative macro-sieve electrodes (MSEs). Methods Dual-electrode assemblies in two configurations [dual macro-sieve electrode-1 (DMSE-I), DMSE-II] were fabricated from pairs of MSEs and implanted in the transected and subsequently repaired sciatic nerves of two male Lewis rats. After four months of postoperative nerve regeneration through the MSEs' transit zones, the efficacy of acute HFAC block was tested for both configurations. Frequencies ranging from 10 kHz to 42 kHz, and stimulus amplitudes with peak-to-peak voltages ranging from 2 V to 20 V were tested. Evoked muscle force measurement was used to quantify the nerve conduction block. Results HFAC stimulation delivered via DMSE assemblies obtained a complete block at frequencies of 14 to 26 kHz and stimulus amplitudes of 12 to 20 V p-p. The threshold voltage for the complete block showed an approximately linear dependence on frequency. The threshold voltage for the partial conduction block was also approximately linear. For those frequencies that displayed both partial and complete block, the partial block thresholds were consistently lower. Conclusion This study provides a proof of concept that regenerative MSEs can achieve complete and reversible conduction block via HFAC stimulation of regenerated nerve tissue. A chronically interfaced DMSE assembly may thereby facilitate the inactivation of targeted nerves in cases wherein pathologic neuronal hyperactivity is involved.

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“…These voltage profiles as well as the artifact at nearby electrodes on the same device were computed based on a reference stimulation current of 1 µA. Mammalian axon models implemented in NEURON (CRRSS nodal dynamics) (Chiu et al 1979, Sweeney et al 1989 representing regenerated and normal axons (Zellmer et al 2017) were used to determine the electrophysiological response of axons in a given radius around the TIME electrode or within the channel of the micro-channel device. The threshold of stimulation current to generate an action potential was determined for each axon being modeled and was used to construct recruitment curves describing the fraction of interfaced axons activated at a given stimulation amplitude.…”

Section: Methodsmentioning

confidence: 99%

Micro-channel sieve electrode for concurrent bidirectional peripheral nerve interface. Part B: stimulation

Coker¹,

Zellmer²,

Moran³

2019

J. Neural Eng.

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Objective. Successful use of a prosthetic limb by an amputee is facilitated by haptic feedback—both a sense of touch and proprioception. Stimulating afferent fibers within peripheral nerves has been shown to provide somatosensation enabling amputees to modulate the control of prosthetic limbs. Peripheral nerve interfaces (PNIs) have also been used to decode patients’ motor intentions. It seems ideal to use PNIs to record efferent fibers for motor control while stimulating afferent fibers to create concurrent sensory feedback. However, while many PNIs claim to be bi-directional, few can both stimulate and record at the same time due to stimulation artifacts which are orders of magnitude larger than the recorded motor signals. This study uses computational modelling to compare the stimulation artifact at threshold levels of stimulation for thin-film transverse intrafascicular multichannel electrodes (tfTIMEs) with micro-channel sieve electrodes. Approach. Finite element models of micro-channel sieves and tfTIMESs were used to solve for electric fields generated during peripheral nerve stimulation. Electrophysiological responses were simulated using axon models. Stimulation artifacts were calculated for stimuli eliciting axonal action potentials. Simulations were carried out for multiple micro-channel geometries and electrode configurations. Main results. Stimulation artifacts generated for threshold stimulation currents are lower for micro-channel devices compared to tfTIMEs. Consequently, stimulus artifacts at threshold currents were substantially higher for the tfTIME. Micro-channel width has a moderate impact on recruitment thresholds and stimulus artifacts. Using the micro-channel sieve in bipolar and tripolar stimulation configurations greatly decreases stimulation artifacts particularly for optimized contact placements (CPs). Electroneurogram (ENG) signals from the companion paper were incorporated showing a great improvement in signal-to-artifact ratio for the micro-channel electrode compared to tfTIMEs. Significance. Stimulating regenerated nerve tissue using micro-channel sieve electrodes can decrease stimulation artifacts and elicit neuronal responses at low stimulation amplitudes. Further analysis provides clues to optimal implementations of micro-channel devices. Finally, stimulation artifacts for simulated tfTIME devices were 2–3 orders of magnitude larger than ENG levels. In contrast, for some micro-channel configurations stimulation artifacts were 3–4 orders of magnitude smaller than ENG levels.

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Modelling the impact of altered axonal morphometry on the response of regenerative nervous tissue to electrical stimulation through macro-sieve electrodes

Cited by 10 publications

References 81 publications

Sensory Percepts Elicited by Chronic Macro-Sieve Electrode Stimulation of the Rat Sciatic Nerve

Sensory Percepts Elicited by Chronic Macro-Sieve Electrode Stimulation of the Rat Sciatic Nerve

High-Frequency Alternating Current Block Using Macro-Sieve Electrodes: A Pilot Study

Micro-channel sieve electrode for concurrent bidirectional peripheral nerve interface. Part B: stimulation

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