A Clinical Feasibility Study of Spinal Evoked Compound Action Potential Estimation Methods

Chakravarthy, Krishnan; FitzGerald, James J.; Will, Andrew; Trutnau, Karen; Corey, Robert M.; Dinsmoor, David; Litvak, Leonid M.

doi:10.1111/ner.13510

Cited by 17 publications

(20 citation statements)

References 23 publications

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“…This software was previously developed to isolate the stimulation artifact from the neural response in clinically acquired ECAP recordings. 24 For both stimulation paradigms, we first removed any stimulation artifact using an exponential modeling method, and then averaged the resulting responses acquired at each stimulation amplitude step (typically 250 responses/step) in the sweep. We determined the amplitude of the ECAP elicited with the LRP by calculating the difference between the N1 and P2 features of the averaged polyphasic ECAPs.…”

Section: Discussionmentioning

confidence: 99%

“…The windows were set given the spacing between the stimulating and recording electrodes and the expected conduction velocity and morphological features of the ECAP in rats. 18,24 For the first stimulation paradigm-50-Hz stimulation with 50-, 100-, 150-, or 200-μs PWs-we generated growth curves for each stimulation amplitude sweep by plotting the measured ECAPs vs the delivered stimulation current. Growth curves are a common graphical means for depicting neural activation, ECAP amplitudes, and the relationship between ECAPs and psychometric measures such as the PT.…”

Section: Discussionmentioning

confidence: 99%

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Spinal Evoked Compound Action Potentials in Rats With Clinically Relevant Stimulation Modalities

Cedeño¹,

Vallejo²,

Kelley³

et al. 2023

Neuromodulation: Technology at the Neural Interface

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Spinal Evoked Compound Action Potentials in Rats With Clinically Relevant Stimulation Modalities

Cedeño¹,

Vallejo²,

Kelley³

et al. 2023

Neuromodulation: Technology at the Neural Interface

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“…The ECAP signal had to be separated from the baseline offset of the stimulation artifact to quantify its RMS magnitude accurately. Neural signal was detrended from stimulation artifact using an exponential based ‘fit and subtract’ approach (Harding, 1991; Chakravarthy et al, 2022; Drebitz et al, 2020). A simple method was used as only ECAPs from Subject 6 microneurography electrode recordings during the cVN dose-response experiment were contaminated by stimulation artifacts.…”

Section: Methodsmentioning

confidence: 99%

Microneurography as a Minimally Invasive Method to Assess Target Engagement During Neuromodulation

Verma

Knudsen

Gholston

et al. 2022

Preprint

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Objective: Peripheral neural signals recorded during neuromodulation therapies provide insights into local neural target engagement and serve as a sensitive biomarker of physiological effect. Although these applications make peripheral recordings important for furthering neuromodulation therapies, the invasive nature of conventional nerve cuffs and longitudinal intrafascicular electrodes (LIFE) limit their clinical utility. Furthermore, cuff electrodes typically record clear asynchronous neural activity in small animal models but not in human-scaled models. Microneurography, a minimally invasive technique, is already used routinely in humans to record asynchronous neural activity in the periphery. However, the relative performance of microneurography microelectrodes, compared to cuff and LIFE electrodes, in measuring neural signals relevant to neuromodulation therapies is not well understood. Approach: To address this gap, we performed cervical vagus nerve evoked compound action potential (ECAP) and spontaneous activity recordings in a human-scaled large animal model - the pig. Additionally, we recorded sensory evoked activity and both invasively and non-invasively evoked CAPs from the great auricular nerve (GAN). In aggregate, this study assesses the potential of microneurography microelectrodes to measure neural activity during neuromodulation therapies with statistically powered and pre-registered outcomes (https://osf.io/y9k6j). Main results: The cuff recorded the largest ECAP signal (p<0.01) and had the lowest noise floor amongst the evaluated electrodes. Despite the lower signal to noise ratio, microneurography microelectrodes were able to detect the threshold for neural activation with similar sensitivity to cuff and LIFE electrodes once a dose-response curve was constructed. Furthermore, the microneurography microelectrode was the only electrode to record distinct sensory evoked neural activity (p<0.01). Significance: The results suggest that microneurography microelectrodes could enable minimally invasive assessment of neural activity for individual subjects. This will further neuromodulation therapies by providing a real-time biomarker to adjust electrode placement and stimulation parameters to optimize the on- to off-target neural fiber engagement and study mechanisms of action.

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“…We analyzed the recorded data offline using custom software developed previously to isolate stimulation artifact from the neural response. 5 For both stimulation configurations, we first removed the stimulation artifact—concurrent with the passive charge recovery phase for the SCS—using an exponential modeling method and then averaged the resulting responses acquired at each stimulation amplitude step in the sweep. We determined the ECAP amplitude by calculating the difference between the N1 and P2 features of the averaged ECAPs.…”

Section: Methodsmentioning

confidence: 99%

Using evoked compound action potentials to quantify differential neural activation with burst and conventional, 40 Hz spinal cord stimulation in ovines

Dinsmoor

Usoro

Barka

et al. 2022

PR9

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Introduction and Objectives: Unlike conventional dorsal spinal cord stimulation (SCS)-which uses single pulses at a fixed rate-burst SCS uses a fixed-rate, five-pulse stimuli cluster as a treatment for chronic pain; mechanistic explanations suggest burst SCS differentially modulate the medial and lateral pain pathways vs conventional SCS. Neural activation differences between burst and conventional SCS are quantifiable with the spinal-evoked compound action potential (ECAP), an electrical measure of synchronous neural activation. Methods: We implanted 7 sheep with a dorsal stimulation lead at T9/T10, a dorsal ECAP sensing lead at T6/T7, and a lead also at T9/T10 but adjacent to the anterolateral system (ALS). Both burst and conventional SCS with stimulation amplitudes up to the visual motor threshold (vMT) were delivered to 3 different dorsal spinal locations, and ECAP thresholds (ECAPTs) were calculated for all combinations. Then, changes in ALS activation were assessed with both types of SCS.Results: Evoked compound action potential thresholds and vMTs were significantly higher (P , 0.05) with conventional vs burst SCS, with no statistical difference (P . 0.05) among stimulation sites. However, the vMT2ECAPT window (a proxy for the useable therapeutic dosing range) was significantly wider (P , 0.05) with conventional vs burst SCS. No significant difference (P . 0.05) in ALS activation was noted between conventional and burst SCS. Conclusion: When dosed equivalently, no differentially unique change in ALS activation results with burst SCS vs conventional SCS; in addition, sub-ECAPT burst SCS results in no discernable excitability changes in the neural pathways feeding pain relevant supraspinal sites.

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A Clinical Feasibility Study of Spinal Evoked Compound Action Potential Estimation Methods

Cited by 17 publications

References 23 publications

Spinal Evoked Compound Action Potentials in Rats With Clinically Relevant Stimulation Modalities

Spinal Evoked Compound Action Potentials in Rats With Clinically Relevant Stimulation Modalities

Microneurography as a Minimally Invasive Method to Assess Target Engagement During Neuromodulation

Using evoked compound action potentials to quantify differential neural activation with burst and conventional, 40 Hz spinal cord stimulation in ovines

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