Comparisons of electrophysiological and psychophysical fitting methods for cochlear implants.

OBJECTIVE: This study compared two different versions of an electrophysiology-based software-guided cochlear implant fitting method with a procedure employing standard clinical software. The two versions used electrically evoked compound action potential (ECAP) thresholds for either five or all twenty-two electrodes to determine sound processor stimulation level profiles. Objective and subjective performance results were compared between software-guided and clinical fittings. DESIGN: Prospective, double-blind, single-subject repeated-measures with permuted ABCA sequences. STUDY SAMPLE: 48 post linguistically deafened adults with ≤15 years of severe-to-profound deafness who were newly unilaterally implanted with a Nucleus device. RESULTS: Speech recognition in noise and quiet was not significantly different between software- guided and standard methods, but there was a visit/learning-effect. However, the 5-electrode method gave scores on the SSQ speech subscale 0.5 points lower than the standard method. Clinicians judged usability for all methods as acceptable, as did subjects for comfort. Analysis of stimulation levels and ECAP thresholds suggested that the 5-electrode method could be refined. CONCLUSIONS: Speech recognition was not inferior using either version of the electrophysiology-based software-guided fitting method compared with the standard method. Subject-reported speech perception was slightly inferior with the five-electrode method. Software-guided methods saved about 10 min of clinician's time versus standard fittings.

Impact of Long-Term Evoked Compound Action Potential Controlled Closed-Loop Spinal Cord Stimulation on Sleep Quality in Patients With Chronic Pain: An EVOKE Randomized Controlled Trial Study Subanalysis.

OBJECTIVE: Spinal cord stimulation (SCS) is considered an effective interventional nonpharmacologic treatment option for several chronic pain conditions. Here we present the effects of the novel evoked compound action potential (ECAP) controlled closed-loop (ECAP-CL) SCS system on long-term sleep quality outcomes from the EVOKE study. MATERIALS AND METHODS: The EVOKE study is a double-blind, randomized, controlled clinical trial conducted at 13 sites in the United States (N = 134 patients). The clinical trial utilized SCS to manage chronic pain and compared novel ECAP-CL technology to open-loop SCS. Additionally, sleep quality data was collected using the Pittsburgh Sleep Quality Index (PSQI) at baseline and all study visits. RESULTS: The mean PSQI global score for ECAP-CL patients at baseline was 14.0 (n = 62; ± 0.5, SD 3.8), indicating poor sleep quality. Clinically meaningful and statistically significant reductions (p < 0.001) in the global PSQI scores were noted at 12 months (n = 55; 5.7 ± 0.6, SD 4.2). A total of 76.4% of ECAP-CL patients met or exceeded Minimal Clinically Important Difference from baseline in PSQI at 12 months. Additionally, 30.9% of ECAP-CL patients achieved "good sleep quality" scores (PSQI ≤ 5), and 29.1% achieved sleep quality remission. "Normative" sleep scores were observed in 29.6% of ECAP-CL patients at 12 months, and these scores were better than the US general population. Additionally, ECAP-CL patients achieved statistically significant changes from baseline (p < 0.01) across all seven subcomponent scores of PSQI at 12 months. CONCLUSIONS: ECAP-CL SCS elicits consistent neural activation of the target leading to less variability in long-term therapy delivery. In the EVOKE study, this resulted in ECAP-CL patients demonstrating clinically superior and sustained pain relief. Results from this study provide new evidence of long-term improvement in sleep quality and quantity in patients with chronic pain resulting from the use of this novel ECAP-CL SCS technology. CLINICAL TRAIL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02924129.

Effect of Proximity to the Modiolus for the Cochlear CI532 Slim Modiolar Electrode Array on Evoked Compound Action Potentials and Programming Levels.

BACKGROUND: The first surgeries with CI532 showed an effect of the proximity of the electrode to the modiolus on the Evoked Compound Action Potentials (ECAPs). OBJECTIVES: Objectives of the study were to investigate the effect of the "pullback" procedure on intraoperative ECAP responses in three different electrode array positions and additionally to compare behavioral thresholds with the thresholds obtained in a group of patients using the standard insertion. The hypothesis of this study is that pullback will cause lower ECAPs and behavioral thresholds. PATIENTS: The study included 40 patients, 20 in the pullback insertion group and 20 in the standard insertion group (without pullback). METHOD: During insertion of the CI532 electrode array, ECAP was performed in three different positions for the pullback group: at initial insertion, at over-insertion, and after pullback. Insertion was monitored by fluoroscopy. In the standard group, ECAP was performed at the initial position, which is also the final position. ECAP thresholds (T-ECAPs) were compared within subjects at the initial and the final position in the pullback group and between groups in the final positions of the pullback and standard groups. Programming levels (C- and T-levels) were compared between the two groups 1 year after switch-on. RESULTS: Intraoperative measurements pullback shows lower average T-ECAPs after pullback compared to thresholds in initial position. Comparison of intraoperative T-ECAPs at the final positions showed no statistically significant difference between the pullback group and the standard insertion group. Furthermore, 1 year after switch-on there was no statistically significant difference in C- and T-levels between the two groups. CONCLUSION: The pullback maneuver of the CI532 electrode array after an over-insertion gave significantly lower T-ECAPs compared to the thresholds at the initial position. However, the between-groups analysis of pullback and standard insertion showed neither significantly different T-ECAPs nor different programming levels. Because T-ECAPs and programming levels vary considerably between subjects, large groups are required to detect differences between groups. Additionally, the effect pullback technique to preserving the residual hearing is not known yet.

Electrically Evoked Compound Action Potentials in Spinal Cord Stimulation: Implications for Preclinical Research Models.

OBJECTIVES: The study aimed to assess the feasibility of recording electrically evoked compound action potentials (ECAPs) from the rat spinal cord. To achieve this, we characterized electrophysiological responses of dorsal column (DC) axons from electrical stimulation and quantified the relationship between ECAP and motor thresholds (ECAPTs and MTs). MATERIAL AND METHODS: Naïve, anesthetized, and freely behaving rats were implanted with a custom-made epidural spinal cord stimulation (SCS) lead. Epidural stimulation and recordings were performed on the same lead using specifically designed equipment. RESULTS: The ECAPs recorded from the rat spinal cord demonstrated the expected triphasic morphology. Using 20 µsec pulse duration and 2 Hz frequency rate, the current required in anesthetized rats to generate ECAPs was 0.13 ± 0.02 mA, while the average current required to observe MT was 1.49 ± 0.14 mA. In unanesthetized rats, the average current required to generate ECAPs was 0.09 ± 0.02 mA, while the average current required to observe MT was 0.27 ± 0.04 mA. Thus, there was a significant difference between the ECAPT and MT in both anesthetized and unanesthetized rats (MT was 13.39 ± 2.40 and 2.84 ± 0.33 times higher than ECAPT, respectively). Signal analysis revealed average conduction velocities (CVs) suggesting that predominantly large, myelinated fibers were activated. In addition, a morphometric evaluation of spinal cord slices indicated that the custom-made lead may preferentially activate DC axons. CONCLUSIONS: This is the first evidence demonstrating the feasibility of recording ECAPs from the rat spinal cord, which may be more useful in determining parameters of SCS in preclinical SCS models than MTs. Thus, this approach may allow for the development of a novel model of SCS in rats with chronic pain that will translate better between animals and humans.

ECAP-Controlled Closed-Loop Spinal Cord Stimulation Efficacy and Opioid Reduction Over 24-Months: Final Results of the Prospective, Multicenter, Open-Label Avalon Study.

INTRODUCTION: Chronic pain is a major public health concern, as is the associated use of opioid medications, highlighting the importance of alternative treatments, such as spinal cord stimulation (SCS). Here, we present the final 24-month results of the Avalon study, which investigated the use of the first closed-loop SCS system in patients with chronic pain. The system measures the evoked compound action potentials (ECAPs) elicited by each stimulus pulse and drives a feedback loop to maintain the ECAP amplitude near constant. METHODS: Fifty patients were implanted with the Evoke system (Saluda Medical) and followed over 24-months. Pain, quality of life (QOL), function, sleep, and medication use were collected at baseline and each scheduled visit. ECAP amplitudes and programming adjustments were also monitored. RESULTS: At 24 months, responder rates (≥ 50% pain reduction) and high responder rates (≥ 80% pain reduction) for overall pain were 89.5% and 68.4%, respectively, the latter up from 42.2% at 3 months. Significant improvements from baseline were observed in QOL, function, and sleep over the 24 months, including ≥ 80% experiencing a minimally important difference in QOL and > 50% experiencing a clinically significant improvement in sleep. At 24 months, 82.8% of patients with baseline opioid use eliminated or reduced their opioid intake. Over the course of the study, reprogramming need fell to an average of less than once a year. CONCLUSION: Over a 24-month period, the Evoke closed-loop SCS maintained its therapeutic efficacy despite a marked reduction in opioid use and steady decrease in the need for reprogramming.

[Simulation study of spinal cord stimulation evoked compound action potential].

Spinal cord stimulation (SCS) for pain is usually implanted as an open loop system using unchanged parameters. To avoid the under and over stimulation caused by lead migration, evoked compound action potentials (ECAP) is used as feedback signal to change the stimulating parameters. This study established a simulation model of ECAP recording to investigate the relationship between ECAP component and dorsal column (DC) fiber recruitment. Finite element model of SCS and multi-compartment model of sensory fiber were coupled to calculate the single fiber action potential (SFAP) caused by single fiber in different spinal cord regions. The synthetized ECAP, superimposition of SFAP, could be considered as an index of DC fiber excitation degree, because the position of crests and amplitude of ECAP corresponds to different fiber diameters. When 10% or less DC fibers were excited, the crests corresponded to fibers with large diameters. When 20% or more DC fibers were excited, ECAP showed a slow conduction crest, which corresponded to fibers with small diameters. The amplitude of this slow conduction crest increased as the stimulating intensity increased while the amplitude of the fast conduction crest almost remained unchanged. Therefore, the simulated ECAP signal in this paper could be used to evaluate the degree of excitation of DC fibers. This SCS-ECAP model may provide theoretical basis for future clinical application of close loop SCS base on ECAP.

The sensitivity of different methods for detecting abnormalities in auditory nerve function.

BACKGROUND: Cochlear implants (CIs) have become important for the treatment of severe-to-profound sensorineural hearing loss (SNHL). Meanwhile, electrically evoked compound action potentials (ECAPs) and electrically evoked auditory brainstem responses (EABRs), which can be examined and evaluated with minimal patient cooperation, have become more reliable for tone measurement and speech recognition postoperatively. However, few studies have compared the electrophysiological characteristics of the auditory nerve using ECAPs and EABRs under different functional states of the auditory nerve (FSANs). We used guinea pig models in which six electrodes were implanted unilaterally with continuous electrical stimulation (ES) for 4 h. The amplitude growth functions (AGFs) of the alternating polarity ECAP (AP-ECAP) and forward-masking subtraction ECAP (FM-ECAP), as well as the EABR waves under "normal" and "abnormal" FSANs, were obtained. RESULTS: Both the AP-ECAP and FM-ECAP thresholds were significantly higher than those measured by EABR under both "normal" FSAN and "abnormal" FSANs (p < 0.05). There was a significant difference in the slope values between electrodes 1 and 2 and electrodes 3 and 4 in terms of the AP-ECAP under the "abnormal" FSAN (p < 0.05). The threshold gaps between the AP-ECAP and FM-ECAP were significantly larger under the "abnormal" FSAN than under the "normal" FSAN (p < 0.05). CONCLUSIONS: Both of the ECAP thresholds were higher than the EABR thresholds. The AP-ECAP was more sensitive than the FM-ECAP under the "abnormal" FSAN.

Evoked Compound Action Potentials Reveal Spinal Cord Dorsal Column Neuroanatomy.

INTRODUCTION: The electrically evoked compound action potential (ECAP) is a measure of the response from a population of fibers to an electrical stimulus. ECAPs can be assessed during spinal cord stimulation (SCS) to elucidate the relationship between stimulation, electrophysiological response, and neuromodulation. This has consequences for the design and programming of SCS devices. METHODS: Sheep were implanted with linear epidural SCS leads. After a stimulating pulse, electrodes recorded ECAPs sequentially as they propagated orthodromically or antidromically. After filtering, amplification, and signal processing, ECAP amplitude and dispersion (width) was measured, and conduction velocity was calculated. Similar clinical data was also collected. A single-neuron computer model that simulated large-diameter sensory axons was used to explore and explain the observations. RESULTS: ECAPs, both animal and human, have a triphasic structure, with P1, N1, and P2 peaks. Conduction velocity in sheep was 109 ms-1 , which indicates that the underlying neural population includes fibers of up to 20 µm in diameter. For travel in both directions, propagation distance was associated with decrease in amplitude and increase in dispersion. Importantly, characteristics of these changes shifted abruptly at various positions along the cord. DISCUSSION: ECAP dispersion increases with propagation distance due to the contribution of slow-conducting small-diameter fibers as the signal propagates away from the source. An analysis of the discontinuities in ECAP dispersion changes with propagation revealed that these are due to the termination of smaller-diameter, slower-conducting fibers at corresponding segmental levels. The implications regarding SCS lead placement, toward the goal of maximizing clinical benefit while minimizing side-effects, are discussed. CONFLICT OF INTEREST: John Parker is the founder and CEO of Saluda Medical and holds stock options. Milan Obradovic, Nastaran Hesam Shariati, Dean M. Karantonis, Peter Single, James Laird-Wah, Robert Gorman and Mark Bickerstaff are employees of Saluda Medical with stock options. At the time the data was collected for the study, Prof. Cousins was a paid consultant for Saluda Medical. John Parker, Milan Obradovic, Dean Karantonis, James Laird-Wah, Robert Gorman and Peter Single are co-inventors in one or more patents related to the topics discussed in this work.

Fine-grain recordings of the electrically evoked compound action potential amplitude growth function in cochlear implant recipients.

BACKGROUND: In cochlear implants (CI) measuring the electrically evoked compound action potential (ECAP) has become an important tool for verifying the electrode-nerve interface as well as establishing a basis for a map to program the speech processor. In a standard clinical setup recordings are averaged over 25-100 repetitions to allow for the detection of ECAPs within the noise floor. To obtain an amplitude growth function, these measurements are normally performed for 5-10 different stimulation levels. We evaluate a recording paradigm where the stimulation intensity is increased in quasi-continuous steps and instead of averaging repeated recordings with identical stimulation parameters, running averages over small intervals of stimulation levels are computed. The first visible nerve response was manually identified by two experts. RESULTS: Both recording paradigms were evaluated in 39 cochlear implants, showing an on average lower threshold of the first nerve response for the quasi-continuous measurement paradigm (Wilcoxon signed-rank test, p = 6.2e-08) compared to the clinical standard paradigm. The mean maximal loudness over all implants and stimulation electrodes was 13% lower at the 80 pulses/s quasi-continuous paradigm compared to the 44 pulses/s clinical standard paradigm. CONCLUSIONS: Beside a more robust determination of the ECAP threshold, the proposed quasi-continuous stimulation paradigm results in a more robust behavioral feedback of the CI user upon the maximal acceptable loudness percept. Furthermore this paradigm can also reveal the fine-structure in the amplitude growth function.

Effective Relief of Pain and Associated Symptoms With Closed-Loop Spinal Cord Stimulation System: Preliminary Results of the Avalon Study.

OBJECTIVES: Conventional spinal cord stimulation (SCS) delivers a fixed-input of energy into the dorsal column. Physiologic effects such as heartbeat, respiration, spinal cord movement, and history of stimulation can cause both the perceived intensity and recruitment of stimulation to increase or decrease, with clinical consequences. A new SCS system controls stimulation dose by measuring the recruitment of fibers in the dorsal column and by using the amplitude of the evoked compound action potentials (ECAPs) to maintain stimulation within an individualized therapeutic range. Safety and efficacy of this closed-loop system was evaluated through six-month postimplantation. MATERIALS AND METHODS: Chronic pain subjects with back and/or leg pain who were successfully trialed received a permanent system (Evoke; Saluda Medical, Sydney, Australia). Ratings of pain (100-mm visual analogue scale [VAS] and Brief Pain Instrument [BPI]), quality of life (EuroQol instrument [EQ-5D-5L]), function (Oswestry Disability Index [ODI]), and sleep (Pittsburgh Sleep Quality Index [PSQI]) were collected at baseline and repeated three and six months after implantation. RESULTS: Fifty-one subjects underwent a trial procedure; permanent implants were placed in 36 subjects. The proportion of subjects with ≥50% relief was 92.6% (back) and 91.3% (leg) at three months, and 85.7% (back) and 82.6% (leg) at six months. The proportion with ≥80% pain relief was 70.4% (back) and 56.5% (leg) at three months, and 64.3% (back) and 60.9% (leg) at six months. Statistically significant improvements in mean BPI, EQ-5D-5L, ODI, and PSQI were also observed at both time points. CONCLUSIONS: The majority of subjects experienced profound pain relief at three and six months, providing preliminary evidence for the effectiveness of the closed-loop SCS system. The exact mechanism of action for these outcomes is still being explored, although one likely hypothesis holds that ECAP feedback control may minimize recruitment of Aß nociceptors and Aδ fibers during daily use of SCS.

[Evoked potentials in the rehabilitation of the patients after cochlear implantation]. / Vyzvannye potentsialy v reabilitatsii patsientov posle kokhlearnoi implantatsii.

The objective methods for the hearing examination of the patients after cochlear implantation provide an important tool for the speech processor fitting. The aim of the present study was to evaluate the possibilities and the informative value of the electrically evoked compound action potential (ECAP) and electrically evoked auditory brainstem response (EABR) combined recording technique. For this reason, the comparison of the ECAP and EABR thresholds with comfortable levels of stimulation, obtained on the basis of subjective response and psychophysical testing of the patients with good results after cochlear implantation was performed. 19 patients with the CI experience from 1 to 5 years were included in our study. The combined registration of ECAP and EABR can be used to evaluate the functional capacity of the central auditory pathways and for the fitting of the complicated patients, especially those in whom the registration proved impossible with the use of other objective techniques. The ECAP and EABR threshold values were well correlated with the individual stimulation map profiles in the patients with the CI experience of less than two years (p<0.05). The results obtained in the present study allow us to conclude that combined registration of ECAP and EABR could be used for the determination of stimulation comfort level parameters and individual stimulation map profiles, especially in combination with the minimum amount of psychoacoustic information received from the patient.

Intraoperative findings on ECAP-measurement: normal or special case?

OBJECTIVE: This study aimed to investigate the measurability and threshold level of electrically evoked compound action potentials (ECAPs) in order to provide a baseline for the development of diagnostic references to support aftercare procedures. DESIGN: In this retrospective study, cochlear implant patients were grouped according to the electrode array type and preoperative diagnostic findings from radiological imaging. ECAP measurements were performed intraoperatively on 22 electrodes for each patient resulting in two comparisons: (1) normal vs. pathological findings based on imaging with same electrode array, (2) perimodiolar electrode vs. straight electrode array within the normal group. STUDY SAMPLE: The study sample consisted of 218 ears with a Nucleus(®) implant. RESULTS: In the group with normal radiological imaging, the percentage of measurable ECAPs was higher than in the pathological group. The ECAP thresholds on 21 electrodes were significantly different between the two groups. Furthermore the thresholds were significantly lower for basal electrodes mainly for the two different electrode types. CONCLUSION: The pathological changes in the inner ear, the type of electrode array, and the electrode position affect the ECAP threshold. Further consideration suggests that a receiver operating characteristic curve can be derived from the results.

A new method for removing artifacts from recordings of the electrically evoked compound action potential: Single-pulse stimulation.

This report presents a new method for removing electrical artifact contamination from the electrically evoked compound action potential (eCAP) evoked by single cathodic-leading, biphasic-pulse stimulation. The development of the new method is motivated by results recorded in human cochlear implant (CI) users showing that the fundamental assumption of the classic forward masking artifact rejection technique is violated in up to 45% of cases tested at high stimulation levels when using default stimulation parameters. Subsequently, the new method developed based on the discovery that a hyperbola best characterizes the artifacts created during stimulation and recording is described. The eCAP waveforms obtained using the new method are compared to those recorded using the classic forward masking technique. The results show that eCAP waveforms obtained using both methods are comparable when the fundamental assumption of the classic forward masking technique is met. In contrast, eCAP amplitudes obtained using the two methods are significantly different when the fundamental assumption of the classic forward masking technique is violated, with greater differences in the eCAP amplitude for greater assumption violations. The new method also has excellent test-retest reliability (Intraclass correlation > 0.98). Overall, the new method is a viable alternative to the classic forward masking technique for obtaining artifact-free eCAPs evoked by single-pulse stimulation in CI users.

Influence of Cochlear Anatomy on Intraoperative Electrically Evoked Compound Action Potentials.

Objective: The electrically evoked compound action potential (ECAP) is an objective measure to indirectly assess spiral ganglion neurons. The ECAP provides inputs about the prognoses of cochlear implant (CI) recipients. Several factors such as cochlear morphology can affect ECAP measurements. This study aims to investigate the variation effect of cochlear parameters on intraoperative ECAP thresholds. Methods: This is a retrospective study on patients who underwent CI surgery with normal inner ear morphology at our center between 2017 and 2023. Cochlear anatomical parameters, including diameter (A value), width (B value), and height (H value), as well as cochlear duct length (CDL), were measured pre-operatively using OTOPLAN software (Version 3.0). Cochlear implant intraoperative objective measures were also collected. The correlation between the cochlear parameters and intraoperative objective measures was studied. Results: A total of 45 patients underwent cochlear implantation. The mean age was 2.4 ± 0.9 years. The mean CDL and cochlear coverage values were 33.2 ± 2.0 mm and 76.0 ± 5.7%, respectively. The ECAP threshold increased toward basal electrodes, with ECAP values as follows: apical 13.1 ± 3.8; middle 14.3 ± 3.7; and basal 15.6 ± 4.8. Additionally, the A, B, and H values showed a positive correlation with ECAP thresholds in different cochlear regions. The B value showed a significant moderate correlation with ECAP thresholds in the middle and basal electrodes but not in the apical electrodes. Conclusions: Cochlear anatomical parameters correlate with intraoperative ECAP thresholds. The B value showed a significant association with ECAP thresholds in the middle and basal electrodes. These findings could delineate the impact of the B value in CI and optimize electrode selection. Further research is required to study this correlation and its impact on postoperative outcomes.

Identifying SCS Trial Responders Immediately After Postoperative Programming with ECAP Dose-Controlled Closed-Loop Therapy.

INTRODUCTION: Drawbacks of fixed-output spinal cord stimulation (SCS) screening trials may lead to compromised trial outcomes and poor predictability of long-term success. Evoked compound action potential (ECAP) dose-controlled closed-loop (CL) SCS allows objective confirmation of therapeutic neural activation and pulse-to-pulse stimulation adjustment. We report on the immediate patient-reported and neurophysiologic treatment response post-physiologic CL-SCS and feasibility of early SCS trial responder prediction. METHODS: Patient-reported pain relief, functional improvement, and willingness to proceed to permanent implant were compared between the day of the trial procedure (Day 0) and end of trial (EOT) for 132 participants in the ECAP Study undergoing a trial stimulation period. ECAP-based neurophysiologic measurements from Day 0 and EOT were compared between responder groups. RESULTS: A high positive predictive value (PPV) was achieved with 98.4% (60/61) of patients successful on the Day 0 evaluation also responding at EOT. The false-positive rate (FPR) was 5.6% (1/18). ECAP-based neurophysiologic measures were not different between patients who passed all Day 0 success criteria ("Day 0 successes") and those who did not ("needed longer to evaluate the therapy"). However, at EOT, responders had higher therapeutic usage and dose levels compared to non-responders. CONCLUSIONS: The high PPV and low FPR of the Day 0 evaluation provide confidence in predicting trial outcomes as early as the day of the procedure. Day 0 trials may be beneficial for reducing patient burden and complication rates associated with extended trials. ECAP dose-controlled CL-SCS therapy may provide objective data and rapid-onset pain relief to improve prognostic ability of SCS trials in predicting outcomes. TRIAL REGISTRATION: The ECAP Study is registered with ClinicalTrials.gov (NCT04319887).

Investigating the Effect of Blurring and Focusing Current in Cochlear Implant Users with the Panoramic ECAP Method.

PURPOSE: For some cochlear implants (CIs), it is possible to focus electrical stimulation by partially returning current from the active electrode to nearby, intra-cochlear electrodes (partial tripolar (pTP) stimulation). Another method achieves the opposite: "blurring" by stimulating multiple electrodes simultaneously. The Panoramic ECAP (PECAP) method provides a platform to investigate their effects in detail by measuring electrically evoked compound action potentials and estimating current spread and neural responsiveness along the length of the CI electrode array. We investigate how sharpening and broadening the electrical current spread are reflected in PECAP estimates. METHODS: PECAP measurements were recorded at most comfortable level in 12 ears of Advanced Bionics CI users. Focused thresholds were also determined. For the electrodes with the highest and lowest focused thresholds, additional PECAP measurements were recorded while stimulating in pTP mode and in "blurred" mode with 3 or 5 adjacent electrodes simultaneously stimulated. Current spread and neural responsiveness were then estimated along the electrode array using PECAP. RESULTS: PECAP revealed increased current spread estimates across participants for blurred stimulation of the targeted electrodes towards the apex of the cochlea. Variable results for pTP stimulation were found, with two of eight ears appearing to drive a small group-level effect of increased current spread. CONCLUSION: When stimulating multiple electrodes simultaneously, PECAP detected localized increases in current spread towards the apex (but not the base) of the cochlea. pTP stimulation showed mixed effects on PECAP current spread estimates. These findings are in line with behavioral speech perception studies and have implications for cochlear implant optimization.

Association Between Intracochlear Electrode Design and Electrically-Evoked Compound Action Potential Measures in Cochlear Implant Users.

OBJECTIVE: Cochlear implant (CI) electrode design has changed over time. Changes in intracochlear electrode design might influence the spread of neural activation along the auditory nerve and the number of independent channels. This study aimed to investigate the impact of intracochlear electrode design on the electrode-neuron interface using electrophysiological measures. STUDY DESIGN: Prospective cohort study. SETTING: A single tertiary hospital. METHODS: Fifty-two ears who were implanted with CI divided into 3 groups based on the design of intracochlear electrode arrays. Twenty-three ears were implanted with lateral wall straight electrodes. Eighteen ears were implanted with the slim perimodiolar electrode, and 11 ears were implanted with the old perimodiolar electrode. Various electrically-evoked compound action potential (ECAP) metrics were measured to quantify spread of excitation and channel interaction. RESULTS: ECAP threshold and slope were not significantly different among groups. ECAP spread of excitation (SOE) half-width and channel interaction index (CII) were significantly larger in subjects implanted with the lateral wall straight electrodes, indicating a wider spread of excitation compared to those with perimodiolar electrodes. Electrode impedance was significantly lower in subjects implanted with perimodiolar electrodes than those with lateral wall electrodes. CONCLUSION: Perimodiolar electrode groups yielded significantly narrower SOE half-widths and smaller CII than the lateral wall straight electrode group. This may indicate that the electrode array that hugged the modiolus had less overlap in neural excitation between adjacent electrodes, resulting in reduced channel interaction and potentially better spectral resolution than the electrode array positioned more laterally.

The role of spinal cord neuroanatomy and the variances of epidurally evoked spinal responses.

BACKGROUND: Spinal cord stimulation (SCS) has demonstrated multiple benefits in treating chronic pain and other clinical disorders related to sensorimotor dysfunctions. However, the underlying mechanisms are still not fully understood, including how electrode placement in relation to the spinal cord neuroanatomy influences epidural spinal recordings (ESRs). To characterize this relationship, this study utilized stimulation applied at various anatomical sections of the spinal column, including at levels of the intervertebral disc and regions correlating to the dorsal root entry zone. METHOD: Two electrode arrays were surgically implanted into the dorsal epidural space of the swine. The stimulation leads were positioned such that the caudal-most electrode contact was at the level of a thoracic intervertebral segment. Intraoperative cone beam computed tomography (CBCT) images were utilized to precisely determine the location of the epidural leads relative to the spinal column. High-resolution microCT imaging and 3D-model reconstructions of the explanted spinal cord illustrated precise positioning and dimensions of the epidural leads in relation to the surrounding neuroanatomy, including the spinal rootlets of the dorsal and ventral columns of the spinal cord. In a separate swine cohort, implanted epidural leads were used for SCS and recording evoked ESRs. RESULTS: Reconstructed 3D-models of the swine spinal cord with epidural lead implants demonstrated considerable distinctions in the dimensions of a single electrode contact on a standard industry epidural stimulation lead compared to dorsal rootlets at the dorsal root entry zone (DREZ). At the intervertebral segment, it was observed that a single electrode contact may cover 20-25% of the DREZ if positioned laterally. Electrode contacts were estimated to be ~0.75 mm from the margins of the DREZ when placed at the midline. Furthermore, ventral rootlets were observed to travel in proximity and parallel to dorsal rootlets at this level prior to separation into their respective sides of the spinal cord. Cathodic stimulation at the level of the intervertebral disc, compared to an 'off-disc' stimulation (7 mm rostral), demonstrated considerable variations in the features of recorded ESRs, such as amplitude and shape, and evoked unintended motor activation at lower stimulation thresholds. This substantial change may be due to the influence of nearby ventral roots. To further illustrate the influence of rootlet activation vs. dorsal column activation, the stimulation lead was displaced laterally at ~2.88 mm from the midline, resulting in variances in both evoked compound action potential (ECAP) components and electromyography (EMG) components in ESRs at lower stimulation thresholds. CONCLUSION: The results of this study suggest that the ECAP and EMG components of recorded ESRs can vary depending on small differences in the location of the stimulating electrodes within the spinal anatomy, such as at the level of the intervertebral segment. Furthermore, the effects of sub-centimeter lateral displacement of the stimulation lead from the midline, leading to significant changes in electrophysiological metrics. The results of this pilot study reveal the importance of the small displacement of the electrodes that can cause significant changes to evoked responses SCS. These results may provide further valuable insights into the underlying mechanisms and assist in optimizing future SCS-related applications.

Evoked compound action potential (ECAP)-controlled closed-loop spinal cord stimulation in an experimental model of neuropathic pain in rats.

BACKGROUND: Preclinical models of spinal cord stimulation (SCS) are lacking objective measurements to inform translationally applicable SCS parameters. The evoked compound action potential (ECAP) represents a measure of dorsal column fiber activation. This measure approximates the onset of SCS-induced sensations in humans and provides effective analgesia when used with ECAP-controlled closed-loop (CL)-SCS systems. Therefore, ECAPs may provide an objective surrogate for SCS dose in preclinical models that may support better understanding of SCS mechanisms and further translations to the clinics. This study assessed, for the first time, the feasibility of recording ECAPs and applying ECAP-controlled CL-SCS in freely behaving rats subjected to an experimental model of neuropathic pain. METHODS: Adult male Sprague-Dawley rats (200-300 g) were subjected to spared nerve injury (SNI). A custom-made six-contact lead was implanted epidurally covering T11-L3, as confirmed by computed tomography or X-ray. A specially designed multi-channel system was used to record ECAPs and to apply ECAP-controlled CL-SCS for 30 min at 50 Hz 200 µs. The responses of dorsal column fibers to SCS were characterized and sensitivity towards mechanical and cold stimuli were assessed to determine analgesic effects from ECAP-controlled CL-SCS. Comparisons between SNI rats and their controls as well as between stimulation parameters were made using omnibus analysis of variance (ANOVA) tests and t-tests. RESULTS: The recorded ECAPs showed the characteristic triphasic morphology and the ECAP amplitude (mV) increased as higher currents (mA) were applied in both SNI animals and controls (SNI SCS-ON and sham SCS-ON). Importantly, the use of ECAP-based SCS dose, implemented in ECAP-controlled CL-SCS, significantly reduced mechanical and cold hypersensitivity in SNI SCS-ON animals through the constant and controlled activation of dorsal column fibers. An analysis of conduction velocities of the evoked signals confirmed the involvement of large, myelinated fibers. CONCLUSIONS: The use of ECAP-based SCS dose implemented in ECAP-controlled CL-SCS produced analgesia in animals subjected to an experimental model of neuropathic pain. This approach may offer a better method for translating SCS parameters between species that will improve understanding of the mechanisms of SCS action to further advance future clinical applications.

Durability of Evoked Compound Action Potential (ECAP)-Controlled, Closed-Loop Spinal Cord Stimulation (SCS) in a Real-World European Chronic Pain Population.

INTRODUCTION: Closed-loop spinal cord stimulation (CL-SCS) is a recently introduced system that records evoked compound action potentials (ECAPs) from the spinal cord elicited by each stimulation pulse and uses this information to automatically adjust the stimulation strength in real time, known as ECAP-controlled SCS. This innovative system compensates for fluctuations in the distance between the epidural leads and the spinal cord by maintaining the neural response (ECAP) at a predetermined target level. This data collection study was designed to assess the performance of the first CL-SCS system in a real-world setting under normal conditions of use in multiple European centers. The study analyzes and presents clinical outcomes and electrophysiological and device data and compares these findings with those reported in earlier pre-market studies of the same system. METHODS: This prospective, multicenter, observational study was conducted in 13 European centers and aimed to gather electrophysiological and device data. The study focused on the real-world application of this system in treating chronic pain affecting the trunk and/or limbs, adhering to standard conditions of use. In addition to collecting and analyzing basic demographic information, the study presents data from the inaugural patient cohort permanently implanted at multiple European centers. RESULTS: A significant decrease in pain intensity was observed for overall back or leg pain scores (verbal numerical rating score [VNRS]) between baseline (mean ± standard error of the mean [SEM]; n = 135; 8.2 ± 0.1), 3 months (n = 93; 2.3 ± 0.2), 6 months (n = 82; 2.5 ± 0.3), and 12 months (n = 76; 2.5 ± 0.3). Comparison of overall pain relief (%) to the AVALON and EVOKE studies showed no significant differences at 3 and 12 months between the real-world data release (RWE; 71.3%; 69.6%) and the AVALON (71.2%; 73.6%) and EVOKE (78.1%; 76.7%) studies. Further investigation was undertaken to objectively characterize the physiological parameters of SCS therapy in this cohort using the metrics of percent time above ECAP threshold (%), dose ratio, and dose accuracy (µV), according to previously described methods. Results showed that a median of 90% (40.7-99.2) of stimuli were above the ECAP threshold, with a dose ratio of 1.3 (1.1-1.4) and dose accuracy of 4.4 µV (0.0-7.1), based on data from 236, 230, and 254 patients, respectively. Thus, across all three metrics, the majority of patients had objective therapy metrics corresponding to the highest levels of pain relief in previously reported studies (usage over threshold > 80%, dose ratio > 1.2, and error < 10 µV). CONCLUSIONS: In conclusion, this study provides valuable insights into the real-world application of the ECAP-controlled CL-SCS system, highlighting its potential for maintaining effective pain relief and objective neurophysiological therapy metrics at levels seen in randomized control trials, and potential for quantifying patient burden associated with SCS system use via patient-device interaction metrics. CLINICAL TRIAL REGISTRATION: In the Netherlands, the study is duly registered on the International Clinical Trials Registry Platform (Trial NL7889). In Germany, the study is duly registered as NCT05272137 and in the United Kingdom as ISCRTN27710516 and has been reviewed by the ethics committee in both countries.