Anodal block permits directional vagus nerve stimulation

Ahmed, Umair; Chang, Yao-Chuan; Cracchiolo, Marina; López, María Fernanda; Tomaio, Jacquelyn N.; Datta-Chaudhuri, Timir; Zanos, Theodoros P.; Rieth, Loren; Al‐Abed, Yousef; Zanos, Stavros

doi:10.1038/s41598-020-66332-y

Cited by 40 publications

(64 citation statements)

References 66 publications

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“…It is worth noting that A-fiber amplitude in these experiments reflects activation of both efferent and afferent A-fibers, which convey sensory information from the lungs. In our experiments, the recording electrode was placed caudally to the stimulating electrode and the stimuli were delivered in the cathodecaudad polarity, promoting the activation of efferent fibers [43]. Using this configuration, it is likely that a significant part of the Afiber component corresponds to activation of efferent A-fibers, as some of the afferent A-fiber activity is blocked by the hyperpolarizing anode [43].…”

Section: Vns Evoked Fiber Activity and Physiological Responsesmentioning

confidence: 99%

“…In our experiments, the recording electrode was placed caudally to the stimulating electrode and the stimuli were delivered in the cathodecaudad polarity, promoting the activation of efferent fibers [43]. Using this configuration, it is likely that a significant part of the Afiber component corresponds to activation of efferent A-fibers, as some of the afferent A-fiber activity is blocked by the hyperpolarizing anode [43]. This would explain the relatively strong linear relationship between A-fiber amplitude and EMG activity, and the weaker relationship with changes in breathing (Fig.…”

Section: Vns Evoked Fiber Activity and Physiological Responsesmentioning

confidence: 99%

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Quantitative estimation of nerve fiber engagement by vagus nerve stimulation using physiological markers

et al. 2020

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Background: Cervical vagus nerve stimulation (VNS) is an emerging bioelectronic treatment for brain, metabolic, cardiovascular and immune disorders. Its desired and off-target effects are mediated by different nerve fiber populations and knowledge of their engagement could guide calibration and monitoring of VNS therapies. Objective: Stimulus-evoked compound action potentials (eCAPs) directly provide fiber engagement information but are currently not feasible in humans. A method to estimate fiber engagement through common, noninvasive physiological readouts could be used in place of eCAP measurements. Methods: In anesthetized rats, we recorded eCAPs while registering acute physiological response markers to VNS: cervical electromyography (EMG), changes in heart rate (DHR) and breathing interval (DBI). Quantitative models were established to capture the relationship between A-, Band C-fiber type activation and those markers, and to quantitatively estimate fiber activation from physiological markers and stimulation parameters. Results: In bivariate analyses, we found that EMG correlates with A-fiber, DHR with B-fiber and DBI with C-fiber activation, in agreement with known physiological functions of the vagus. We compiled multivariate models for quantitative estimation of fiber engagement from these markers and stimulation parameters. Finally, we compiled frequency gain models that allow estimation of fiber engagement at a wide range of VNS frequencies. Our models, after calibration in humans, could provide noninvasive estimation of fiber engagement in current and future therapeutic applications of VNS.

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Section: Vns Evoked Fiber Activity and Physiological Responsesmentioning

confidence: 99%

Section: Vns Evoked Fiber Activity and Physiological Responsesmentioning

confidence: 99%

Quantitative estimation of nerve fiber engagement by vagus nerve stimulation using physiological markers

et al. 2020

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“…By recording evoked compound action potentials through a second implanted nanoclip on the same nerve, they showed that current-steered stimulation modulated songbird vocalizations more precisely than bulk stimulation, and that different spatial patterns of stimulation reliably activated different subsets of nerve fibers. This is important because many peripheral nerves, such as the vagus nerve, contain several different calibers and types of fibers, each associated with different physiological functions (Ahmed et al 2020 ). Therefore, the ability to achieve fiber-specificity through patterned neurostimulation works to maximize desired end-organ specific changes, while minimizing potential off-target side effects.…”

Section: Main Textmentioning

confidence: 99%

Changing the tune using bioelectronics

Chang

2021

Bioelectron Med

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The desire to harness electricity for improving human health dates back at least two millennia. As electrical signals form the basis of communication within our nervous system, the ability to monitor, control, and precisely deliver electricity within our bodies holds great promise for treating disease. The nascent field of bioelectronic medicine capitalizes on this approach to improve human health, however, challenges remain in relating electrical nerve activity to physiological function. To overcome these challenges, we need more long-term studies on neural circuits where the nerve activity and physiological output is well-established. In this Letter, I highlight a recent study that takes just such an approach.

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“…Knowledge of threshold intensities is essential in neuromodulation studies and therapies. The threshold for a given stimulation modality varies widely across subjects 16, 17 . Mechanisms that determine threshold can be grouped into 3 categories: those related to the neural interface, those related to the generated electrical field, and those related to the physiological status of the end-organ.…”

Section: Introductionmentioning

confidence: 99%

“…Factors that determine the neural interface include surgical technique 2, 11 , foreign body response to a long-term implanted electrode 1, 8 19 , and degradation of the electrode itself 20 . Factors influencing the generated electrical field include electrode geometry 21 22 , electrode orientation relative to the stimulated neural elements 17, 21, 23 , and stimulation parameters 11, 21 . Finally, the state of a subject or the end-organ at the time of stimulation affects the stimulation threshold 24 .…”

Section: Introductionmentioning

confidence: 99%

Implant- and anesthesia-related factors affecting threshold intensities for vagus nerve stimulation

Ahmed

Chang

López

et al. 2021

Preprint

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Vagus nerve stimulation (VNS) is used as therapy in epilepsy and depression and is tested as a potential treatment for several chronic disorders. Typically, VNS is delivered at increasing stimulus intensity until a response is observed (threshold intensity). Factors that affect threshold intensities for engagement of different fiber types and concomitant physiological responses have not been studied. We determined neural and physiological responses to increasing stimulus intensities of VNS in anesthetized and awake animals, and examined the effect of implant- and anesthesia-related factors on threshold intensities in a rodent model of VNS. In acute and long-term cervical vagus nerve implants (53 and 14 rats, respectively) VNS was delivered under isoflurane, ketamine-xylazine, or awake at different intensities. Stimulus-evoked compound action potentials (eCAPs) were recorded, elicited physiological responses were registered, including changes heart rate (HR), breathing, and blood pressure (BP), and threshold intensities were determined. The intensity that elicits eCAPs (“neural threshold”) is significantly lower than what elicits a physiological response (“physiological threshold”, PT) (25 μA ±1.8 vs. 70 μA ±5.2, respectively; Mean ±SEM). Changes in BP occur at the lowest stimulus intensities (80 μA ±7), followed by changes in HR (105 μA ±8.4) and finally in breathing (310 μA ±32.5). PT is lower with than without electrode insulation (60 μA ±12, vs. 700 μA ±123). PT and electrode impedance are correlated in long-term (r=0.47; p<0.001) but not in acute implants (r=-0.34; p NS); both PT and impedance increase with implant age (Pearson correlation r=0.44; p<0.001 and r=0.64; p<0.001, respectively). PT is lowest when animals are awake (210 μA ±33; Mean ±SEM), followed by ketamine-xylazine (630 μA ±154), and isoflurane (1075 μA ±131). The sequence of physiological responses with increasing VNS intensity is similar in both anesthetized and awake states. Implant age, electrical impedance and the type of anesthesia affect VNS threshold and should be accounted for when determining stimulation dose.

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Anodal block permits directional vagus nerve stimulation

Abstract: Threshold-intensity (122 trains) Supra-threshold intensity (75 trains) C. caud. C. ceph. Pol. diff. C. caud. C. ceph. Pol. diff.

Cited by 40 publications

References 66 publications

Quantitative estimation of nerve fiber engagement by vagus nerve stimulation using physiological markers

Quantitative estimation of nerve fiber engagement by vagus nerve stimulation using physiological markers

Changing the tune using bioelectronics

Implant- and anesthesia-related factors affecting threshold intensities for vagus nerve stimulation

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