Binaural Cue Sensitivity in Children and Adults With Combined Electric and Acoustic Stimulation
Phase: NA
Conditions: Cochlear Implant, Hearing Loss
Sponsor: Hearts for Hearing

Principal Investigator: Jourdan Holder, AuD PhD 
 
Date: 02/27/2025 
Study Title: Binaural cue sensitivity in children and adults with combined electric and acoustic stimulation 
Institution/Hospital: VUMC 
NCT 
 
Protocol Version #: 3 
 
1 
Protocol Date: 02/27/2025 
 
 
 
 
 
 
 
 
Binaural cue sensitivity in children and adults with combined 
electric and acoustic stimulation 
 
NIH NIDCD R01 DC020194 
 
 
 
 
 
 
 
 
 
 
 
 
 
PI: Jourdan Holder, AuD PhD 
Department Chair: Anne Marie Tharpe, PhD 
Department of Hearing and Speech Sciences 
Vanderbilt University Medical Center 
 
 
 
 
 
 
 
 
 
 
 
 

Principal Investigator: Jourdan Holder, AuD PhD 
 
Date: 02/27/2025 
Study Title: Binaural cue sensitivity in children and adults with combined electric and acoustic stimulation 
Institution/Hospital: VUMC 
NCT 
 
Protocol Version #: 3 
 
2 
Protocol Date: 02/27/2025 
 
 
Table of Contents: 
 
Study Schema 
1.0 
Background 
2.0 
Rationale and Specific Aims 
3.0 
Animal Studies and Previous Human Studies 
4.0 
Inclusion/Exclusion Criteria 
5.0 
Enrollment/Randomization 
6.0 
Study Procedures 
7.0 
Risks of Investigational Agents/Devices (side effects) 
8.0 
Reporting of Adverse Events or Unanticipated Problems involving Risk to 
Participants or Others 
9.0 
Study Withdrawal/Discontinuation 
10.0 Statistical Considerations 
11.0 Privacy/Confidentiality Issues 
12.0 Follow-up and Record Retention 

Principal Investigator: Jourdan Holder, AuD PhD 
 
Date: 02/27/2025 
Study Title: Binaural cue sensitivity in children and adults with combined electric and acoustic stimulation 
Institution/Hospital: VUMC 
NCT 
 
Protocol Version #: 3 
 
3 
Protocol Date: 02/27/2025 
1.0 
Background 
Combined Electric and binaural Acoustic Stimulation (EAS), achieved via hearing 
preservation cochlear implantation, has become increasingly prevalent. Two cochlear implant 
(CI) systems have specific FDA labeling for EAS allowing for normal low-frequency (LF) hearing 
with precipitously sloping high-frequency (HF) hearing loss, and all three FDA-approved systems 
have integrated hearing aid (HA) circuitry in ear-level sound processors. Despite wide 
availability of EAS technology and an abundance of studies reporting high rates of long-term 
hearing preservation11–13, only 50-69% of adult CI users with acoustic hearing preservation are 
utilizing EAS technology14,15; however, we found that from 2013-2018, adult EAS technology 
utilization increased from 36% to 69% and our hearing preservation rates improved from 57% 
to 95% over that same period15. Thus, there is evidence that hearing preservation and EAS 
utilization will continue to increase. In addition to the availability of EAS technology, the 
combination of bilateral HAs with CI (CI+HAbilat) provides significant additional benefit beyond 
that offered by bimodal hearing (CI+HAcontra) for speech understanding in noise3–7,16, 
reverberation4, music listening17, and localization3,7,8. However, there is considerable variability 
in EAS benefit across listeners and different listening environments. This variability in EAS 
benefit is not reliably related to low-frequency audibility in the CI ear(s)8,9—a finding also 
observed in the bimodal literature. That is, despite a correlation (r=0.25-0.35) between bimodal 
benefit and audiometric thresholds in the non-CI ear, bimodal benefit for individuals with 
unaided thresholds from 40-100 dB HL ranges from a negative impact (bimodal interference) to 
over 60-percentage points of benefit for speech in noise18,19. Given the increased emphasis on 
hearing preservation cochlear implantation and accompanying EAS technology available for all 
CI recipients, there is a clear impetus for us to understand the underlying auditory mechanisms 
and to extract the relevant clinical applications to assist clinical management of EAS users today 
and tomorrow.  
 
 
Low-frequency ITDs & ILDs for spatial hearing: EAS users have binaural acoustic 
hearing in the low-to-mid frequencies offering access to ITDs—which are most prominent for 
frequencies below 1500 Hz20–22. In contrast, ILDs are largest above 1500 Hz23, but still present 
for LF stimuli in the range of ~2-6 dB23. Adult EAS users demonstrate ITD thresholds for 
acoustic stimuli in the ecologically relevant range4,8,9,24, with some EAS users exhibiting near-
normal ITD sensitivity. Because most EAS users have a unilateral CI with precipitously sloping 
HF hearing losses, HF ILDs are generally not available; rather, bilateral acoustic audibility for 
most adult EAS users is limited above ~750 Hz due to audiometric configuration and 
severity2,4,8,25–27.  
Adult EAS users also show significantly better localization in listening conditions including 
bilateral HAs and EAS (CI+HAbilat) as compared to the within-subjects bimodal condition 
(CI+HAcontra)3,7,8. EAS users can also access ITDs4,8,9,24 and said ITD thresholds are significantly 
correlated with localization8 and speech recognition in diffuse noise4,8,9. We have also shown 
that acoustic hearing in the CI ear offers significant benefit for spatial hearing tasks involving 
static cues such as minimal audible angle (MAA) as well as dynamic cues such as the minimal 
audible movement angle (MAMA) (see Preliminary Studies). In fact, we show that localization 
(rms error), MAA (degrees), MAMA (degrees), and speech recognition in diffuse noise in the 
EAS condition are all related to LF ITD and ILD sensitivity9; however, only the correlation for 
ITDs reached statistical significance9. These data provide evidence that at least some individuals 
with hearing preservation can use LF ITDs and ILDs, despite the fact that ITD and ILD 
sensitivity is generally poorer than what would be expected for age-matched listeners with NH9. 

Principal Investigator: Jourdan Holder, AuD PhD 
 
Date: 02/27/2025 
Study Title: Binaural cue sensitivity in children and adults with combined electric and acoustic stimulation 
Institution/Hospital: VUMC 
NCT 
 
Protocol Version #: 3 
 
4 
Protocol Date: 02/27/2025 
Additionally, these data demonstrate that EAS users can take advantage of underlying binaural 
cues—most notably LF ITDs—using their clinical EAS technology in free-field environments 
despite the lack of interaural synchronization3–5,7,8.  
 
Contributions of ITDs and ILDs to EAS benefit: Though adult EAS listeners appear 
to use both ITDs and ILDs to obtain significant EAS benefit for tasks of spatial hearing tasks 
and speech understanding, we do not know how these listeners weight LF ITD and ILD cues, 
particularly as related to degree of interaural asymmetry and absolute audibility differences 
across the acoustic-hearing spectrum. It is well known that interaural asymmetry in audibility 
can disrupt binaural cue sensitivity subsequently resulting in spatial hearing deficits28. In fact, 
interaural asymmetry is known to drive changes in the weighting of ITD/ILD cues29 resulting in 
poor binaural cue integration30; however, adult humans31–33 and animals34 have demonstrated 
adaptation to asymmetry over time with evidence of at least partial restoration of binaural 
function. This holds high clinical relevance for the technological design and clinical programming 
of HAs and CIs. Though loudness balancing across ears via frequency-specific amplification is 
critical for access to both ITDs and ILDs, there are other clinical considerations for HA and CI 
parametric manipulation. To make such data-driven decisions regarding development, 
programming, and management of HA and CI technology, we must have a thorough 
understanding of the underlying mechanisms driving EAS benefit (or lack thereof) for both 
adults and children. 
Pediatric EAS and binaural development: Binaural hearing is central to several 
critical auditory phenomena including localization, speech recognition in complex environments, 
speech/music perception and appreciation, as well as quality of life. The role of binaural 
stimulation for auditory development is critical as inhibitory synapses in the central auditory 
system are refined throughout infancy and early childhood. The effectiveness of developmental 
synaptic pruning is dependent upon typical activation of excitatory auditory pathways, or 
consistent binaural input35. For children with hearing loss, binaural development can be 
significantly impacted as auditory deprivation degrades both 
ITD and ILD coding36,37. Figure 1 displays an anatomical 
schematic of cochlear, auditory brainstem, midbrain, and 
brain structures including cochlear nucleus (CN), lateral 
superior olive (LSO), medial superior olive (MSO), inferior 
colliculus (IC), medial geniculate nucleus (MGN), and 
auditory cortex (AC). In Figure 1A, unilateral CI with 
acoustic hearing preservation (CI+HAbilat) preserves ITDs and 
LF ILDs via LF acoustic hearing; LSO shading is transparent 
here (Fig. 1A) indicating only partial ILD availability via LF 
acoustic hearing. In Figure 1B, bilateral CIs with bilateral 
HAs (CIbilat+HAbilat), preserves ITDs and LF ILDs via acoustic 
hearing, but also transmits more robust HF ILDs via bilateral 
CIs38. In both scenarios, resolution of binaural cues is possible, but the hearing configuration in 
Figure 1B, offers maximum availability of ITDs and ILDs. As displayed here, chronic EAS use in 
children could drive developmental changes in binaural excitatory and inhibitory pathways as 
well as the perceptual weighting of ITD and ILD cues. Indeed, greater EAS utilization across all 
populations, could significantly improve spatial hearing abilities for both adults and children. 
There is limited research on hearing preservation for pediatric CI users, particularly 
related to functional outcomes and EAS benefit. All but one recent study39 has focused on 

Principal Investigator: Jourdan Holder, AuD PhD 
 
Date: 02/27/2025 
Study Title: Binaural cue sensitivity in children and adults with combined electric and acoustic stimulation 
Institution/Hospital: VUMC 
NCT 
 
Protocol Version #: 3 
 
5 
Protocol Date: 02/27/2025 
pediatric hearing preservation describing whether it was achieved, rather than describing EAS 
benefit for speech recognition or spatial hearing40–48. For studies reporting speech 
recognition45,49–53, none investigated whether acoustic hearing from the CI ear provided 
significant additional advantage over that afforded by acoustic hearing from the non-CI ear 
(CI+HAbilat vs. CI+HAcontra). We must understand how children use binaural acoustic hearing 
with CI, what constitutes realistic and expected EAS outcomes for speech recognition and 
spatial hearing, and what device configurations yield maximum outcomes; these are critical 
concerns for children developing binaural hearing, speech and language, as well as social and 
emotional skills, musical abilities, and academic proficiency.  
 
Deprivation-driven neuroplasticity: Animal and human research demonstrates 
remarkable neuroplastic changes in response to binaural deprivation, particularly when 
deprivation coincides with critical periods of auditory development28,30,31,35,54–56. Deprivation-
driven remapping of the binaural hearing system persists long after asymmetries in binaural 
hearing have been corrected. The implication of this research is that optimizing EAS as early as 
possible and within critical periods of development will most potently shape binaural hearing 
and support basic processes that we know to be important for spatial hearing abilities. 
However, we know little about the impact of bilateral hearing loss—particularly asymmetric LF 
hearing loss resulting from threshold elevation following CI surgery—on binaural development 
in humans. While some tasks of binaural hearing—such as mean MAA and localization in quiet—
are adult-like in early childhood57–60, other aspects of binaural hearing continue to develop 
through adolescence10. Children with NH also exhibit considerable variability in rms error59 as 
well as significant uncertainty and immature decision-masking strategies on tasks of binaural 
cue sensitivity61. In addition to these binaural developmental effects for children with NH, little 
is known about the trajectory of binaural development in children with hearing loss who have 
access to binaural acoustic hearing. Specifically, we do not know what additional effects hearing 
loss, interaural asymmetry in acoustic hearing, and the addition of unilateral electrical 
stimulation may have on the developing binaural system. Gorodensky and colleagues29 showed 
lateralization was significantly affected by hearing loss severity for 32 children and that 
interaural asymmetry negatively influenced ITD- and ILD-based lateralization. It may be the 
case that younger children experience limited utilization of the binaural cues that likely subserve 
adult EAS benefit in complex listening environments, as described in Preliminary Studies. In 
fact, our pilot data suggest that children who are experienced bimodal listeners (CI+HAcontra) do 
not demonstrate acute EAS benefits (CI+HAbilat) when initially fitted with acoustic amplification 
in the implanted ear(s); however, we show data for three children with chronic EAS use (3+ 
years) who exhibit significant EAS benefit comparable to adults; 1 of these 3 children was 
followed longitudinally and demonstrated emergence of EAS benefit and binaural sensitivity 
following a 4-year period of chronic EAS use. Thus, there is a critical gap in the literature 
regarding the typical trajectory for binaural development for both children with NH as well as 
children with bilateral hearing loss, with or without CI.  
As mentioned above, binaural development could be influenced by a unilateral CI, which 
is the typical intervention for individuals with EAS-like audiograms. For NH listeners, across-
frequency incongruencies in binaural cues result in elevated ITD and ILD thresholds62–65. 
Similarly, a unilateral CI could cause binaural interference resulting in disruption of LF acoustic 
cues as shown in our recent study with EAS simulations66. However, in contrast to our binaural 
interference data with EAS simulations, few adult EAS listeners exhibit binaural interference for 
ITD and/or ILD targets when using a unilateral CI9. For the few adult EAS listeners who did 

Principal Investigator: Jourdan Holder, AuD PhD 
 
Date: 02/27/2025 
Study Title: Binaural cue sensitivity in children and adults with combined electric and acoustic stimulation 
Institution/Hospital: VUMC 
NCT 
 
Protocol Version #: 3 
 
6 
Protocol Date: 02/27/2025 
exhibit binaural interference, the effect was variable and not related to binaural cue sensitivity 
in the acoustic-alone condition, absolute target audibility, or degree of interaural asymmetry in 
audibility9. Thus, it is possible that chronic EAS use with unilateral CI (CI+HAbilat) allows for 
adaptation to the presence of a constant, but binaurally incongruous CI stimulus, as shown in 
Figure 1A. It is also plausible that bilateral CI with bilateral hearing preservation (CIbilat+HAbilat) 
(Figure 1B), results in better preservation of binaural cue sensitivity and spatial hearing 
abilities given access to LF ITDs as well as both LF and HF ILDs. Investigation of these effects is 
warranted in both adults and children as these data could significantly impact clinical 
recommendations and audiological management of EAS patients. As more adults and children 
with EAS-qualifying audiograms pursue bilateral CIs and have bilateral hearing 
preservation44,48,67,68, sequential bilateral implantation occurring within our enrolled study 
participants would allow a naturalistic investigation of these effects in both groups. This 
investigation can inform clinical practice regarding recommendations for EAS or bilateral CI for 
children with bilateral sloping sensorineural hearing loss (SNHL); this project will provide the 
necessary data to help guide these critical clinical decisions. 
To understand the contributions of LF binaural cues to EAS, we will assess the relative 
weighting of ITD and ILD cues as well as compare this weighting to spatial hearing tasks 
completed in the free field, where cues naturally co-vary. This comparison will be of particular 
importance to pediatric EAS listeners whose head size and central nervous system maturation 
both continue to change through adolescence. With the physical growth in head size69 and the 
known developmental maturation of neural synchrony or phase locking70,71—a critical 
component for resolution of fine-structure ITDs—we expect children with NH and EAS to exhibit 
immature spatial hearing abilities in conditions involving roving level58,59,72, and children using 
EAS to have poor ITD sensitivity resulting from bilateral SNHL and interaural asymmetry for LF 
audibility39 (also see Figure 4—Preliminary Studies). Though ITD sensitivity for infants with NH 
rapidly improves from birth to approximately 50 weeks of age73–75, adult-like ITD thresholds10 
and decision-making strategies61 may not be achieved until adolescence. Though there is 
research demonstrating adult-like lateralization and resolution based on both ITD and ILD 
cues71,76 and adult-like spatial discrimination for some tasks57, we know little about perceptual 
weighting, and developmental trajectories of binaural hearing even for children with NH. 
 
 Sensory and non-sensory factors: There is likely a difference between sensory-
based maturation, as evidenced by infant studies, and some combination of sensory and non-
sensory maturation influencing a child’s ability to complete behavioral tasks of spatial 
discrimination and spatial release from masking (SRM). This gap in our knowledge about the 
developmental trajectory of binaural cue sensitivity, perceptual weighting of said cues, and 
underlying neural synchrony influencing LF ITD access complicates interpretation of the current 
literature regarding sensory- and non-sensory factors. As little as we know about development 
of binaural cue sensitivity in children with NH, we know even less for children with bilateral 
SNHL. Our proposed research will describe the developmental nature of binaural sensitivity and 
spatial hearing abilities in children with NH and EAS. Further we will characterize the influence 
of bilateral SNHL as well as interaural hearing asymmetry on binaural cue sensitivity providing 
theoretical value to the field regarding binaural development. This information will inform 
hearing technology development and have the potential to improve clinical EAS fittings, thereby 
holding high public health relevance for CI recipients with bilateral LF acoustic hearing.  
 

Principal Investigator: Jourdan Holder, AuD PhD 
 
Date: 02/27/2025 
Study Title: Binaural cue sensitivity in children and adults with combined electric and acoustic stimulation 
Institution/Hospital: VUMC 
NCT 
 
Protocol Version #: 3 
 
7 
Protocol Date: 02/27/2025 
Clinically applicable measure identifying EAS benefit: Despite significant EAS 
benefit for speech recognition in noise, reverberation, and spatial hearing, utilization of EAS 
technology for CI users with hearing preservation is just 50-69% for adults14,15 and there are no 
published reports for children. As previously mentioned, though EAS benefit is significant, it is 
variable across listeners and not well predicted by the audiogram. This poses a clinical quandary 
for audiologists who are unsure who to fit with EAS technology, particularly given that many 
adult CI recipients reject the use of an earmold or non-custom dome in the CI ear. One cited 
reason is that the CI alone yields significant auditory benefit and CI users already obtain 
adjunctive benefit from bimodal hearing (CI+HAcontra). Clinicians need a measure capable of 
identifying individuals who are most likely to derive significant EAS benefit (CI+HAbilat) from 
availability of LF acoustic ITDs and/or ILDs. Such a measure would inform clinical decisions 
regarding EAS fitting and would provide a springboard for counseling patients who may be 
reluctant to add another piece of hearing technology. 
We have demonstrated a significant correlation between adult EAS benefit for speech in 
noise, spatial discrimination, auditory motion perception, and EAS listeners’ sensitivity to 
ITDs4,8,9 and ILDs in the acoustic-hearing domain9. However, psychophysical estimates of ITD 
and ILD sensitivity can take hours and require a period of listener training for accurate 
estimation. Although research-proven tasks can inform us regarding potential for EAS benefit, 
use of said tasks is just not clinically feasible. Rather, audiologists need a quick and sensitive 
measure indicative of binaural cue utilization. Such a measure could be integrated into the pre- 
and/or post-operative test battery informing us about which listeners are most likely to derive 
benefit from bilateral acoustic amplification in an EAS configuration (CI+HAbilat) and could also 
help inform implant electrode array selection, surgical approach, and medical management to 
maximize hearing preservation.  
 
Behavioral measures: The binaural masking level difference (BMLD) and binaural 
intelligibility level difference (BILD) tasks have the potential to serve as clinically feasible, 
functional assessments of binaural cue utilization for EAS patients. BMLD is the phenomenon in 
which a lower threshold is observed in conditions for which the signal and masker differ in 
interaural phase77–79 and the BILD is a similar phenomenon using speech stimuli as the target. 
We currently have pilot data for BMLD with 250- and 500-Hz tones in the presence of a LF noise 
(100 to 800 Hz) and spondee BILD in the presence of a broad-band noise (BBN). As described 
in Preliminary Studies, we found that both BMLD and BILD magnitude was significantly 
correlated with EAS benefit obtained for speech recognition in diffuse noise (S0N45-315) as well as 
for tasks of spatial hearing—including MAA and MAMA; this relationship is key to understanding 
binaural mechanisms. There has also been increased attention on the translation of research-
proven tasks of psychophysical auditory perception to clinically feasible assessments with a 
quick behavioral ITD task being particularly relevant here80–83.  
 
Objective measures: In addition to behavioral measures of binaural sensitivity or 
binaural cue utilization, there are relevant objective measures which may prove useful for 
clinical application. These objective measures can be categorized based on the approximate 
“level” of the binaural auditory system that they test from brainstem to cortex. While binaural 
hearing undoubtedly begins in the brainstem, brainstem-based metrics may be confounded by 
methodological issues that make them difficult to interpret [see So and Smith84 for discussion]. 
This has led many researchers to favor cortical assays of binaural hearing, which reflect 
brainstem-initiated processes inherited by higher-order auditory structures. Research in listeners 
with NH has demonstrated that sensitivity to interaural phase differences (IPDs85,86), ITDs87,88, 

Principal Investigator: Jourdan Holder, AuD PhD 
 
Date: 02/27/2025 
Study Title: Binaural cue sensitivity in children and adults with combined electric and acoustic stimulation 
Institution/Hospital: VUMC 
NCT 
 
Protocol Version #: 3 
 
8 
Protocol Date: 02/27/2025 
and ILDs88 are indexed in cortically evoked acoustic change complexes (ACC). ACCs in response 
to the introduction of a binaural shift in phase (ACCIPD), time (ACCITD), or level (ACCILD) indicate 
that the listener has the neural capacity to discriminate the imposed change; however, the 
binaurally elicited ACC does not necessarily translate to behavioral sensitivity of said cue. 
Figure 6 in Preliminary Studies displays representative ACCIPD waveforms and correlations with 
behavioral ITDs. Because research has shown significant relationships between ACC86 or 
interaural phase modulation following response (IPM-FR85) and spatial listening and/or BMLD 
tasks in adult listeners with NH, there is evidence that these objective measures are reasonable 
surrogates for binaural perceptual abilities.  
The possibility of using an objective measure of binaural processing holds promise for 
determining which CI users with hearing preservation are equipped to derive benefit from 
bilateral LF amplification via EAS (CI+HAbilat). This work will allow us to 1) investigate the 
relationship between IPD- and ILD-evoked ACC in adult and pediatric EAS users, 2) complete a 
parametric and longitudinal investigation into the emergence of this response in children with 
NH89,90 and children with bilateral SNHL, and 3) compare electrophysiologic measures to 
behavioral estimates of binaural cue sensitivity and ITD/ILD cue weighting. Characterizing 
neural synchrony via phase coherence (see Approach) from these objective measures will 
provide the field with information regarding the potential differences between underlying 
physiological sensitivity (sensory factors) and a child’s ability to complete tasks of spatial 
hearing (sensory and non-sensory factors). Though rapid technological and surgical advances 
have made it possible for many patients to utilize EAS, individual and mechanistic factors 
contributing to EAS benefit are still unclear. Our proposed research activities will help close the 
gap between what is technologically possible and what is clinically implemented by investigating 
development of binaural sensitivity and spatial hearing. The resultant data can be used to 
exploit developmentally driven timing and level cues to maximize EAS technology and related 
hearing outcomes. 
 
INNOVATION: This innovative proposal will significantly impact the field by providing the first 
dataset explaining: 1) degree and time course of EAS benefit in pediatric and adult CI users 
following EAS fitting; 2) developmental trajectory of binaural auditory sensitivity in children with 
NH and EAS; 3) perceptual weighting of binaural cues in adult and pediatric EAS users including 
a description of weighting over time for children and adults initially fit with EAS technology; 4) 
development of clinically relevant behavioral and objective assessments that can inform clinical-
decision making for EAS application. We will use data from Aims 1 and 2 to help describe the 
time course of binaural development using behavioral and objective responses to interaural 
differences in timing (phase) and level. New insight into the developmental trajectory of the 
binaural system for children with NH will provide a benchmark for interpreting effects of SNHL, 
LF asymmetry in audibility, and presence of electrical stimulation on said trajectory. The 
theoretical framework of our primary outcome measures—EAS benefit for speech recognition 
and spatial hearing—is outlined in Figure 2.  
In Aim 2, we will gain an understanding of the expected 
magnitude of EAS benefit across a wide range of CI-recipient 
ages and hearing configurations as well an understanding of 
which measures may aid clinical decision making regarding 
successful application of EAS technology. Use of an accelerated 
longitudinal design will allow us to investigate natural factor 
variations following a clinical intervention—the EAS fitting—that 

Principal Investigator: Jourdan Holder, AuD PhD 
 
Date: 02/27/2025 
Study Title: Binaural cue sensitivity in children and adults with combined electric and acoustic stimulation 
Institution/Hospital: VUMC 
NCT 
 
Protocol Version #: 3 
 
9 
Protocol Date: 02/27/2025 
can be harnessed via mediation analysis (Figure 2). This will allow us to study mechanisms of 
binaural development in children with SNHL using EAS (CI+HAbilat and CIbilat+HAbilat). Finally, the 
data obtained from this proposal hold high impact for identification of measures that may be 
used in a clinical environment to identify patients best suited for EAS benefit. This latter point is 
critical given that EAS fittings are underutilized. 
Finally, this proposal has great innovation in the investigative team which brings 
together a psychoacoustician and clinical audiologist with experience working with EAS patients 
(Holder), a psychoacoustician and developmental auditory scientist with over 20 years’ 
experience working with adults and children with NH and bilateral CIs (Litovsky), and an 
electrophysiologist and clinical audiologist who has been focused on objective estimates of 
binaural function in listeners with NH (Smith). The expertise of this team brings tremendous 
synergy to the proposed investigation of theoretical and clinical questions for this rapidly 
growing EAS population. This team will be able to provide the first comprehensive description of 
behavioral and electrophysiologic measures of binaural hearing in adults and children with NH 
and EAS and will uncover information about our EAS clinical population holding high potential 
for clinical application in device fittings as well as audiologic and otologic clinical 
recommendations regarding cochlear implantation.  
 
 
PRELIMINARY STUDIES 
EAS benefit for adult and pediatric listeners: We recruited 6 CI recipients (5-16 
years) with acoustic hearing preservation in the CI ears39. Speech recognition was tested in the 
CI-only, bimodal (CI+HAcontra), and EAS (CI+HAbilat) conditions. Only 2 of 6 participants had 
chronic EAS experience; the others were fitted and 
tested acutely. CI-only and bimodal conditions used 
a full electric bandwidth, typical for non-EAS fittings. 
Sentence recognition in noise was assessed with the 
R-SPACETM system including 8 loudspeakers in a 
circular pattern (S0N45-315). Sentence recognition was 
assessed via adaptive speech reception threshold 
(SRT) for Hearing In Noise Test (HINT91) sentences 
as well as for a fixed signal-to-noise ratio (SNR) 
ranging from +2 to +15 dB for Pediatric AzBio 
sentences (commonly referred to as BabyBio92). The 
pediatric EAS data reported in Roberts et al.39 are 
displayed in the right-hand column of Figure 3 with 
BabyBio scores transformed to rationalized arcsine 
units (RAU)93. The left-hand column displays a 
similar dataset for 31 adult EAS users for AzBio sentences at +5 dB SNR (RAU) and adaptive 
HINT SRT—portions of this adult dataset appear in our preliminary studies5,19. For BabyBio in 
noise, none of the children exhibited significant EAS benefit considering the 95% confidence 
interval for sentence test-retest variability92,94; however, 
ceiling effects likely played a role for half the sample. For 
adult EAS, 12 of 31 (39%) demonstrated significant EAS 
benefit with mean benefit of 13.0-percentage points 
(averaged across the 31 subjects). For adaptive HINT, just 
1 child in our paper39 exhibited significant EAS benefit 
whereas adult EAS users demonstrated a mean 3.2-dB 

Principal Investigator: Jourdan Holder, AuD PhD 
 
Date: 02/27/2025 
Study Title: Binaural cue sensitivity in children and adults with combined electric and acoustic stimulation 
Institution/Hospital: VUMC 
NCT 
 
Protocol Version #: 3 
 
10 
Protocol Date: 02/27/2025 
benefit (range 0-6 dB4,5). Since the original submission, we have collected additional data from 
3 pediatric EAS users as follows: 1) 8.3-year old who was one of the original 6 participants in 
our pediatric EAS paper39 but who now has 2 additional years of EAS experience, 2) 7.2-year 
old with 6 years’ EAS experience, and 3) 6.5-year old fitted with EAS and tested acutely. Newly 
collected data are displayed in green (Fig. 3) with dashed lines representing all children with 
3+ years of EAS experience. For adaptive HINT, all children with 3+ years EAS use exhibited 
EAS benefit ranging from 2.8 to 4.2 dB (mean: 3.3 dB)—which is comparable to our observed 
adult EAS benefit5.  
Figure 4 highlights the developmental effect on behavioral ITD thresholds for a 250-Hz 
tone. For 20 children with NH (circles), the mean ITD threshold was 361.3 ms and there was an 
inverse correlation between ITD threshold and age (r=-0.61, p=0.0026). For EAS users, an ITD 
threshold could not be tracked for 3 of 5 children as reported in our paper39. For the 3 EAS 
users with 3+ years EAS use (7.2, 8.3, and 16.2 years—represented by stars and bold square), 
ITD thresholds were comparable to NH children in the same age range (Fig. 4). The bilateral 
chronic EAS user (green star) followed over time, showed emergence of ITD sensitivity at 8.3 
years (Fig. 4). ITD thresholds for the 2 additional EAS listeners recruited since the last 
submission (7.2 and 6.5 years) are displayed as purple and pink stars, respectively.  
Emergence of EAS benefit and binaural cue sensitivity: We now have extensive 
data for 3 children with chronic EAS experience (3+ years). One is an 8.3-year old bilateral EAS 
user (CIbilat+HAbilat) followed in the lab annually since CI activation (green star in Figs. 4 & 5). 
At the first 2 study visits, she exhibited no binaural cue sensitivity with ITD thresholds > 1000 
ms (Fig. 4) and no EAS benefit for speech recognition in diffuse noise. However, after 4 years 
of chronic EAS use, her ITD threshold at 250 Hz was 765 ms (Fig. 4) and she showed EAS 
benefit of 3.5 dB (HINT) and a 6-dB BILD. While her behavioral ITD threshold does not reflect 
ecologically relevant sensitivity, she demonstrated emergence of this skill which translated to 
functional EAS benefit. The 2 additional new EAS recruits (6.5- and 7.2-years old) were also 
tested on tasks of ITD threshold (Fig. 4) and BILD. Only the 7.2-year old with 6 years’ EAS 
experience tracked an ITD threshold (720 ms) and also had 3.0-dB EAS benefit for HINT SRT; 
however, both newly recruited children exhibited a significant BILD (mean: 4.0 dB)—even the 
6.5-year old tested immediately following EAS fitting. This is a critical finding as we show 
evidence that pediatric EAS benefit resulting from binaural cue sensitivity and binaural cue 
utilization likely emerges over time following chronic EAS use. 
Figure 5 displays speech recognition for BKB-SIN95 
in co-located (S0N0) and spatially separated symmetric 
noise (S0N90,180,270) for 8 bilateral CI (5-12 years), 10 
bimodal (6-15 years), and 2 children with chronic EAS use 
(7.2- and 8.3-years old, also see Figs. 3-4). Though all 
groups demonstrated similar SRM, the EAS listeners 
outperformed the other groups and the bilateral EAS 
listener (green star) approached NH performance, even in 
symmetrical noise which does not offer head shadow.  
Tasks of spatial hearing and BMLD/BILD: We 
have data for adult EAS listeners in the bimodal 
(CI+HAcontra) and EAS (CI+HAbilat) conditions on tasks of horizontal plane localization (n=14)8, 
MAA (n = 12), and MAMA (20 deg/sec; n = 20) for a BBN (100-8000 Hz) and LF noise (LFN; 
100-800 Hz). We found that adding acoustic hearing in the CI ear yielded a significant 

Principal Investigator: Jourdan Holder, AuD PhD 
 
Date: 02/27/2025 
Study Title: Binaural cue sensitivity in children and adults with combined electric and acoustic stimulation 
Institution/Hospital: VUMC 
NCT 
 
Protocol Version #: 3 
 
11 
Protocol Date: 02/27/2025 
improvement in spatial hearing abilities. We also observed a significant correlation between 
spatial hearing abilities in the EAS condition for both stimuli (LFN & BBN) and ITD thresholds for 
localization (r=0.89 & 0.27), MAA (r=0.35 & 0.25), and MAMA (r=0.57 & 0.60). Our MAA and 
MAMA manuscripts are currently in preparation.  
BMLD and BILD tasks are functional measures of binaural cue utilization as a lower (i.e., 
better) threshold is observed in conditions for which the signal and masker differ in interaural 
phase79. BMLD data were collected for acoustic-alone hearing via insert earphones. The signal 
was either a 250- or 500-Hz tone and adaptive procedure tracked 70.7% correct96. BILD was 
measured with spondees via single interval, also tracking 70.7% correct96. The tonal or spondee 
signal was presented as phase correlated (N0S0) and phase inverted (N0S
), relative to the 
masker. Our adult pilot data (n=7) showed lower masked thresholds for the phase-inverted 
signal (N0S
) for 5 of 7 adult EAS users at 250 Hz and for all 4 adult EAS users tested at 500 
Hz. Though preliminary, those deriving the greatest EAS benefit for speech recognition in noise 
(S0N45-315) also exhibited the greatest BMLD (r=0.5-0.6). We also obtained BILD thresholds for 8 
adult EAS and 3 pediatric EAS users. For adult EAS, there was a strong correlation between 
BILD and EAS benefit (r=0.91, p=0.0002). For pediatric EAS, all 3 children exhibited significant 
BILD (mean = 4.0), but only the 2 children with chronic EAS use (7.2 and 8.3 years) exhibited 
EAS benefit for speech recognition. For the 6.5-year old fitted and tested acutely, she exhibited 
a 3.5-dB BILD, but no EAS benefit for speech recognition and no viable ITD threshold (> 1000 
ms). Given that this acutely fitted child exhibited a significant BILD, it is quite possible we will 
observe an emergence of EAS benefit and ITD sensitivity following a period of chronic EAS use. 
These pilot data suggest that a relatively simple and quick BMLD/BILD task could be used 
clinically to determine which CI recipients with hearing preservation would most likely obtain 
significant EAS benefit. 
CAEPs (ACCIPD): To date, we have tested 5 adult EAS listeners on measures of 
behavioral ITD sensitivity, speech understanding in diffuse noise, spatial hearing (MAA), and 
ACCIPD. To validate test protocols and verify feasibility, CAEPs were also obtained for a group of 
7 younger (23 to 35 years) and 2 older (46 to 62 
years) listeners with NH. Pilot data were collected 
using the IHS DUET with a 2-channel recording 
with 4 Ag-AgCl scalp electrodes at Cz (+), A1/A2 
(-), and Fz (gnd). The stimulus was a 1.6-sec, 
250-Hz tone that was sinusoidally amplitude 
modulated at 40 Hz. The SAM tone was 
presented either diotically for the entire 1.6-
second duration or had a 180-degree IPD applied 
at the SAM null at 0.8 sec (in one ear) to elicit 
the ACCIPD. The presentation level was 90 dB SPL 
for EAS listeners and 70 dB SPL for NH listeners. 
Two runs of 128 sweeps were averaged for each 
condition. Preliminary data demonstrate that the 
ACCIPD was measurable in the 0.8- to 1.2-sec 
range, for all NH listeners and measurable for our EAS listeners with the best psychophysical 
ITD thresholds. Figure 6 displays mean CAEP waveforms for the diotic and dichotic stimuli—
with IPD change in right (red) or left (blue) ear—for the 7 younger and 2 older listeners with 
NH, as well as representative data for an EAS listener with good ITD sensitivity (103 ms for 

Principal Investigator: Jourdan Holder, AuD PhD 
 
Date: 02/27/2025 
Study Title: Binaural cue sensitivity in children and adults with combined electric and acoustic stimulation 
Institution/Hospital: VUMC 
NCT 
 
Protocol Version #: 3 
 
12 
Protocol Date: 02/27/2025 
250-Hz tone) and an EAS listener with poor ITD sensitivity (>1600 ms at 250 Hz). In addition to 
obtaining feasibility data, we also observed a trending correlation between ACCIPD magnitude 
and behavioral ITDs (r=-0.82) as well as with EAS speech recognition in diffuse noise (r=0.71), 
and EAS MAA (r=0.81). These pilot data suggest that the use of ACCIPD could help identify CI 
users with bilateral acoustic hearing who might benefit from EAS and could potentially even be 
administered in the preoperative period to gauge binaural cue sensitivity. Such a measure could 
even be useful for surgeons who might select electrode arrays, steroid dosing, and surgical 
approaches to maximize hearing preservation for those with greatest potential for EAS benefit. 
 
2.0 
Rationale and Specific Aims 
 
Approximately 83-92% of adult cochlear implant (CI) recipients with aidable low-
frequency (LF) hearing have acoustic hearing preservation1,2 affording Electric and binaural 
Acoustic Stimulation (EAS). Numerous studies have shown EAS benefit for adult CI users using 
bilateral hearing aids (HA; CI+HAbilat) for speech understanding in complex environments3–7 as 
well as spatial hearing in static and dynamic conditions3,7,8. We have shown that adult EAS 
users’ sensitivity to interaural time difference (ITD) and interaural level difference (ILD) cues is 
correlated with EAS benefit for both speech recognition and spatial hearing, and that binaural 
cue sensitivity may predict EAS benefit even for clinical EAS technology which lacks interaural 
synchronization4,8,9. Despite this active phase of discovery, much about EAS is poorly 
understood, yet critically important for maximizing outcomes via clinical management of HAs 
and CIs. We are also seeing growing numbers of pediatric CI users with hearing preservation; 
however, due to limited research on pediatric EAS outcomes, we do not know the expected 
trajectory of EAS benefit, underlying mechanisms driving binaural hearing and EAS benefit in 
this population, as well as the impact of a CI paired with bilateral HAs on binaural development. 
These knowledge gaps are critical given that adult EAS listeners are known to use both ITDs 
and ILDs for improved speech recognition in diffuse noise and spatial hearing9. Thus, it is 
important to know what is driving binaural development in pediatric EAS users—in the presence 
of bilateral LF hearing loss and central auditory immaturities in binaural processing—particularly 
given evidence that some aspects of binaural hearing continue to develop through adolescence, 
even for children with normal hearing (NH)10. 
Technological advances are outpacing scientific discovery impacting our ability to deliver 
evidence-based recommendations and audiologic management for a growing EAS population. 
Our pilot data show EAS benefit immediately following activation for adults, but no acute EAS 
benefit for children; however, we also provide evidence for emergence of EAS benefit and 
binaural sensitivity in children following a period of chronic EAS use. Given the protracted 
maturation of the binaural system, we must understand what additional effects hearing loss, 
acoustic LF interaural asymmetry, and electrical stimulation may have on the developing 
binaural system for both scientific and clinical applications. Thus, we propose two independent 
aims using behavioral and objective measures in adult and pediatric EAS users as well as age- 
and hearing-matched children and adults with NH. The proposed accelerated longitudinal design 
allows for a natural factor investigation of a clinical intervention (EAS fitting) via mediation 
analysis. In this clinical trial, we will define acute and chronic EAS outcomes for speech 
recognition and spatial hearing as related to binaural cue sensitivity, developmental binaural 
cue weighting, and underlying neural synchrony necessary for ITD resolution.  
 

Principal Investigator: Jourdan Holder, AuD PhD 
 
Date: 02/27/2025 
Study Title: Binaural cue sensitivity in children and adults with combined electric and acoustic stimulation 
Institution/Hospital: VUMC 
NCT 
 
Protocol Version #: 3 
 
13 
Protocol Date: 02/27/2025 
AIM 1: Emergence of binaural cue sensitivity in EAS users. We will investigate 
emergence of binaural sensitivity for ITD and ILD cues as well as ITD/ILD cue weighting, which 
is critical for children with developing binaural function and underlying neural synchronization. 
Hypotheses: 1a) Pediatric EAS users will demonstrate an emergence of binaural cue sensitivity 
following a period of chronic EAS use incorporating bilateral LF acoustic amplification, 1b) there 
will be a relationship between listener age and ITD/ILD weighting for lateralization with the 
youngest EAS candidates assigning greater weight to ILDs due to immaturities in neural 
synchronization, and 1c) the time course of pediatric acoustic ITD/ILD development will be 
correlated with absolute and interaural auditory sensitivity for LF acoustic hearing.  
 
 
AIM 2: Degree and time course of EAS benefit for speech and spatial 
discrimination informed by behavioral and objective estimates of binaural cue 
utilization. We will describe EAS listener performance (CI+HAbilat) and EAS benefit (CI+HAbilat - 
CI+HAcontra) for (1) tasks of speech recognition in co-located, diffuse, and spatially separated 
noise, and (2) tasks of spatial discrimination. We will relate these to ITD/ILD sensitivity 
measured both behaviorally (Aim 1) and electrophysiologically (Aim 2) via cortical auditory 
evoked potentials (CAEPs) reflecting brainstem-initiated processes inherited by the central 
auditory system. Hypotheses: 2a) EAS benefit will be observed for speech recognition and 
spatial discrimination with chronic EAS use, which will be mediated by access to LF ITD cues 
estimated via both behavioral and objective measures, and 2b) there will be a relationship 
between behavioral and objective measures of binaural cue utilization and EAS benefit for 
speech recognition and spatial hearing. 
 
IMPACT: Integration of HA and CI technology has resulted in a rapidly growing EAS 
population. While some may question long-term EAS benefit, we are in a unique position to 
study this intervention which offers what neither bilateral CIs nor bimodal hearing can provide—
access to LF ITDs. This project offers an exciting opportunity to study the emergence of 
binaural cue sensitivity in children with EAS compared with adult EAS users. We will formulate a 
novel understanding of auditory factors influencing sensitivity to binaural cues and perceptual 
factors influencing said sensitivity. Our diverse and collaborative team of psychoacousticians 
(Holder, Litovsky), audiologists (Holder, Smith), a binaural developmental scientist (Litovsky), 
and an electrophysiologist (Smith) is what makes this innovative and clinically translational 
proposal possible." 
 
 
3.0 
Animal Studies and Previous Human Studies 
 
N/a 
 
4.0 
Inclusion/Exclusion Criteria 
 
We anticipate enrollment of up to 200 study participants (50 recruited for each group) to 
account for 25% attrition and achieve our target goal of 160 completed participants with 40 in 
each of the following groups: pediatric EAS, adult EAS, pediatric NH, adult NH. Note that the 
adult NH listeners will be recruited and tested at a single study visit. The majority of our EAS 
study participants will be enrolled at Vanderbilt with a smaller number enrolled at UW Madison. 
Testing of EAS participants will be done at both Vanderbilt and UW-Madison. Pediatric NH 
participants will be recruited and enrolled at Vanderbilt, UW-Madison, and UT-Austin. Adult NH 

Principal Investigator: Jourdan Holder, AuD PhD 
 
Date: 02/27/2025 
Study Title: Binaural cue sensitivity in children and adults with combined electric and acoustic stimulation 
Institution/Hospital: VUMC 
NCT 
 
Protocol Version #: 3 
 
14 
Protocol Date: 02/27/2025 
participants will be recruited and enrolled at Vanderbilt and UT Austin. All research participants 
will be paid for their participation.  
 
Inclusion criteria for EAS participants: 
• 
Pediatric EAS: aged 5 to 17 years, at enrollment; Adult EAS: aged 18+ years 
(NOTE: there is no upper age limit provided that the individual demonstrates a 
passing score on the MoCA or HI-MoCA cognitive screener) 
o Pediatric EAS participants will be recruited evenly across the following 
enrollment ages expressed in years:months as follows: 5:0 to 6:11, 7:0 
to 8:11, 9:0 to 10:11, 11:0 to 12:11, and 13:0 to 17:11. 
• 
Accounting for attrition, we plan to recruit 48 participants across the five age 
ranges to achieve a complete set of 40 participants.  
• 
At least one CI or a CI candidate in at least 1 ear and bilateral mild to 
profound sensorineural hearing loss with unaided audiometric thresholds  80 
dB HL at 125 and 250 Hz, in both ears. 
• 
Willingness to use EAS technology in the implanted ear(s) to be verified via 
data logging 
• 
Nonverbal cognitive abilities within the typical range 
• 
No co-morbid diagnoses such as autism, auditory neuropathy, neurological 
disorder, or general cognitive impairment 
• 
Use of spoken English as main mode of communication 
 
Exclusion criteria for EAS participants: 
• 
Single-sided deafness (SSD) 
• 
Nonverbal intelligence standard score < 85 (KBIT-2) 
o Should a participant score < 85 on KBIT-2, we will recommend that 
the participant be seen by their primary care provider to obtain an 
appropriate referral. 
• 
HI-MoCA score < 26 (for adult EAS participants) 
o Should a participant score < 26 on HI-MoCA, we will recommend that 
the participant be seen by their primary care provider to obtain an 
appropriate referral. 
 
Inclusion criteria for NH participants: 
• 
Pediatric NH: aged 5 to 17 years, at enrollment; Adult NH: aged 18+ years 
(NOTE: there is no upper age limit provided that the individual demonstrates a 
passing score of MoCA or HI-MoCA cognitive screener) 
• 
Adult NH listeners will be recruited to match the age range of the adult EAS 
participants and assessed at a single study visit. 
• 
Pediatric NH listeners will be recruited evenly across the following enrollment 
ages expressed in years:months as follows: 5:0 to 6:11, 7:0 to 8:11, 9:0 to 
10:11, 11:0 to 12:11, and 13:0 to 17:11. 
• 
Accounting for attrition, we plant to recruit 48 participants across the five age 
ranges to achieve a complete set of 40 participants. 
• 
Pediatric NH participants will have audiometric thresholds  20 dB HL from 
125 through 8000 Hz, in octave steps. 

Principal Investigator: Jourdan Holder, AuD PhD 
 
Date: 02/27/2025 
Study Title: Binaural cue sensitivity in children and adults with combined electric and acoustic stimulation 
Institution/Hospital: VUMC 
NCT 
 
Protocol Version #: 3 
 
15 
Protocol Date: 02/27/2025 
• 
Adult NH participants will have audiometric thresholds  25 dB HL from 125 to 
4000 Hz, though higher frequency thresholds will also be obtained and 
recorded.  
• 
nonverbal cognitive abilities within the typical range 
• 
no confounding diagnosis such as autism, auditory neuropathy, neurological 
disorder, or general cognitive impairment 
• 
Use of spoken English as main mode of communication 
 
Exclusion criteria for NH participants: 
• 
nonverbal intelligence standard score < 85 (KBIT-2) 
o Should a participant score < 85 on KBIT-2, we will recommend that 
the participant be seen by their primary care provider to obtain an 
appropriate referral. 
• 
MoCA score < 26 (adult NH participants) 
o Should a participant score < 26 on MoCA, we will recommend that 
the participant be seen by their primary care provider to obtain an 
appropriate referral. 
 
5.0 
Enrollment/Randomization 
 
Participants will be identified via electronic medical record chart review and discussion amongst 
our clinical cochlear implant team regarding newly scheduled cochlear implant candidates. All 
participants will complete the proposed research activities and thus there will be no 
randomization or blinding/masking. Potential study participants will be approached via 
telephone or email prior to a scheduled clinic visit or in the audiology clinic at their 
appointment. Contact will be completed by the clinical coordinator or research personnel. 
Participants will be made aware that participation is optional and will not impact the clinical care 
they receive at VUMC.   
 
6.0 
Study Procedures 
 
APPROACH 
Participants: We are proposing a clinical trial including 4 groups—2 experimental 
(pediatric & adult EAS) and 2 control (pediatric & adult NH); we will focus on within-subjects 
analyses given the longitudinal nature of the design and the inherent differences between the 
pediatric and adult populations. NH participants are included for normative benchmarking. We 
will recruit 40 pediatric EAS users aged 5-17 years (~70% followed longitudinally at VUMC and 
30% at UW-Madison, reflecting differential size of clinical CI programs, budgeted effort across 
sites, and air travel accessibility). This age range was chosen to be representative of most 
children receiving CIs with acoustic hearing preservation who are generally older at 
implantation as they exceed the conventional audiometric profile for cochlear implantation47. 
Also, all children in our preliminary and pilot studies were in this range and were able to 
complete the proposed test battery. We will also recruit 40 NH children in the same 
chronologic- and hearing-age range, with 1/3 recruited and followed at each of 3 sites (VUMC, 
UW Madison, UT Austin). None of the children will have confounding diagnoses such as autism, 
auditory neuropathy, or cognitive impairment. EAS participants must have at least 1 CI and 

Principal Investigator: Jourdan Holder, AuD PhD 
 
Date: 02/27/2025 
Study Title: Binaural cue sensitivity in children and adults with combined electric and acoustic stimulation 
Institution/Hospital: VUMC 
NCT 
 
Protocol Version #: 3 
 
16 
Protocol Date: 02/27/2025 
acoustic hearing in the implanted ear(s). We will also recruit 40 adult EAS users (~80% 
followed at VUMC, 20% at UW-Madison, based on the respective sizes of our clinical CI 
programs and air travel accessibility) as well as 40 age-matched NH adults. The adult NH group 
will be seen for a single experimental time point to establish normative data with ½ enrolled 
and followed by VUMC and the other ½ at UT Austin. 
Both adult and pediatric EAS users will be recruited beginning at or very close to 
implantation allowing for an assessment of the impact of the electric stimulation on ITD and ILD 
sensitivity longitudinally following surgery and activation. This will allow us to investigate 
whether EAS users adapt to a unilateral “distracter” stimulus over time, or in other words, 
overcome the effects of binaural interference demonstrated by listeners with NH66. Enrolling at 
or close to CI activation within this longitudinal design will allow us to complete a natural factor 
investigation of a clinical intervention, the EAS fitting, via mediation analysis as displayed in 
Figure 2. Relatedly, we will also collect and store child/family variables known to influence 
hearing, speech, and language outcomes for children with SNHL including age at assessment, 
age at CI, age at identification, etiology, CI wear time (via datalogging), nonverbal IQ, maternal 
level of education, socioeconomic status, family size, and preschool educational environment 
(i.e., mainstream preschool, parent-infant program, etc.) These variables may be used in data 
analysis as covariates or to subdivide groups for descriptive analyses. 
Experimental design: Children will be recruited based on age at enrollment via 
accelerated longitudinal design, allowing us to study binaural development longitudinally over a 
5-year period for children aged 5-17 years. To ensure an even distribution of chronological age, 
we will recruit evenly across the following 5 age ranges expressed in years:months as follows: 
5:0 to 6:11, 7:0 to 8:11, 9:0 to 10:11, 11:0 to 12:11, and 13:0 to 17:11. We plan to complete 
4-postoperative visits for each child over 2 years, spaced in 6-month intervals in the 1st  year 
and a 1-year interval thereafter. Adult EAS users will be seen over 3 time points following 
activation beginning at or within 1 month of CI activation with 2 additional visits spaced in 6-
month intervals. See Table 1 in Human Subjects for a visual timeline of research activities. All 
EAS users will ideally be recruited prior to implantation allowing for the investigation of pre- and 
post-operative binaural sensitivity—though the pre-operative session is not reflected in Table 1 
as it is not a requirement for study inclusion.  
Clinical battery: Clinical testing will be completed for all CI users including unaided 
pure-tone audiometry and aided speech recognition via CNC97 words, AzBio94 or BabyBio92 
sentences at +5 dB SNR, and BKB-SIN95. Listening conditions include bilateral HAs, CI-alone, 
bimodal (CI+HAcontra), and EAS (CI+HAbilat). To assess functional communication and spatial 
hearing, we will administer the Speech, Spatial, and Qualities (SSQ98) questionnaire to adults 
and the parent or child SSQ99 for pediatric participants aged 5-10 and 11+ years, respectively. 
Adults will be required to pass a cognitive screener via the Montreal Cognitive Assessment 
(MoCA100) or the MoCA hearing-impaired version (HI-MoCA101) for EAS users. For all 
participants, we will also assess non-verbal intelligence using the KBIT-2102 as well as auditory 
working memory over time via the Numbers Reversed from the Woodcock-Johnson IV (WJ-
IV103). We will also assess receptive language for all children (NH and EAS) annually using the 
Receptive One-Word Picture Vocabulary Test-4 (ROWPVT-4104) and the Clinical Evaluation of 
Language Fundamentals (CELF-5105). A certified SLP at VUMC will train investigators and 
administer audio- and video-recorded assessments.  
Programming & verification of HA & CI: Acoustic amplification will be applied for LF 
stimuli with audiometric thresholds up to 90 dB HL—as specified by the software for all EAS 

Principal Investigator: Jourdan Holder, AuD PhD 
 
Date: 02/27/2025 
Study Title: Binaural cue sensitivity in children and adults with combined electric and acoustic stimulation 
Institution/Hospital: VUMC 
NCT 
 
Protocol Version #: 3 
 
17 
Protocol Date: 02/27/2025 
Standard 
ITD = 0 µsec
Center
ITD = 0 µsec
Target
ITD ¹ 0 µsec
Correct answer
feedback
Figure 7: Panels A & B are displayed as the penguin’s hops are synchronized with 
binaurally presented stimuli at ITD = 0 µs (penguin in center). When penguin disappears 
(panel C), the third “target” tone is presented with a left or right-leading ITD. After the 
listener selects the moving direction of the target tone (i.e., left or right iceberg), correct 
answer feedback is provided (panel D).
systems. Regardless of one’s unaided thresholds above 1000 Hz, we will limit the HA response 
to 1000 Hz thereby restricting acoustic amplification to the frequency region over which ITDs 
are most robust106. HA settings will be verified via real-ear measures verifying target audibility 
for DSL v5.0 Child107 for children and NAL-NL2108 for adults. We will also obtain CI-aided 
thresholds requiring aided thresholds to be in the range of 20-30 dB HL from 250 through 6000 
Hz. CI and HA equipment will be verified at all visits prior to experimentation. For participants 
with LF thresholds > 45 dB HL in CI ear(s), custom earmolds will be fitted for LF acoustic 
amplification. EAS crossover frequency will be manipulated for all EAS users using 3 LF CI 
cutoffs corresponding to 1) full electrical bandwidth (full EAS overlap), 2) audiometric frequency 
corresponding to a 70-dB-HL threshold (minimal EAS overlap—largely consistent with clinical 
EAS programming software), and 3) the audiometric frequency corresponding to 90 dB HL (no 
EAS overlap). These 3 conditions will afford comparison to existing adult EAS data5,109 for 
speech recognition in Aim 2 and will build our sample for experimental populations and will 
inform clinical practice guidelines. 
 
AIM 1: ITD/ILD sensitivity and cue weighting: ITD and ILD thresholds will be 
measured using tonal and noise-band carriers. Pure tones will be 250 and 500 Hz and noise 
stimuli will include BBN (100-8000 Hz) and LF noise (100-800 Hz). BBN will be a Gaussian noise 
burst, band-pass filtered from 100 to 
8000 Hz to encompass the frequency 
range transmitted by CI processors. LF 
noise will be filtered from 100-800 Hz 
including attenuation of 48 dB/oct. 
Stimulus duration will be 300 ms with 
10-ms cos2 ramping. Stimuli will be 
delivered acoustically via ER-3A 
earphones at a fixed level (EAS: 90 dB 
SPL; NH: 70 dB SPL) and fixed sensation level (SL; 20 dB SL) across ears. We will complete this 
task using both acoustic only and EAS stimulation with the latter via direct connection to the CI 
sound processor allowing for investigation of binaural interference and comparison to adult data 
from our previous studies9. Fixed-SL testing will be determined from the audiogram using 
frequency specific HL-to-SPL corrections at octave and inter-octave frequencies within the noise 
band. Equal SL will be applied to the acoustic stimuli via inserts; the stimulus delivered to the CI 
processor will be presented unprocessed at a level of 65 dB SPL. A cued 3-interval, 2-alternative 
forced-choice procedure will be used as described by Peng and colleagues61. Figure 7 displays 
the video game interface we will use for this task for pediatric participants; note that we will not 
utilize eye tracking as 20 children have successfully completed this task behaviorally61. Figures 
7 A & B prompt “get ready to listen” as the penguin dives in the water (Figure 7C). The child 
is asked to indicate which iceberg the penguin is hiding behind and correct answer feedback is 
shown in Figure 7D. Level will be roved to help avoid monaural level cues. A method of 
constant stimuli will be used to estimate ITD and ILD sensitivity over a range of ITDs and ILDs: 
ITDs: 0, ±50, ±100, ±200, ±400, and ±800 msec; and ILDs: 0, ±1.5, ±3, ±6, ±9, ±15, and 
±20 dB. For adult participants, we will also use a method of constant stimuli with the same 
ranges of ITDs and ILDs; however, we will use a standard visual interface displaying illuminated 
squares on a screen representing the cued 3-interval, 2-alternative forced-choice paradigm. For 
all listeners, thresholds will be estimated at 70% correct on a standard logit function using the 
MATLAB function glmfit.  

Principal Investigator: Jourdan Holder, AuD PhD 
 
Date: 02/27/2025 
Study Title: Binaural cue sensitivity in children and adults with combined electric and acoustic stimulation 
Institution/Hospital: VUMC 
NCT 
 
Protocol Version #: 3 
 
18 
Protocol Date: 02/27/2025 
ITD/ILD cue weighting—lateralization paradigm: We will investigate ITD and ILD cue 
weighting within a lateralization task in which we will independently vary ITD and ILD for the 
same stimuli described above (BBN & LF noise). ITDs and ILDs will vary over the same ranges 
described above. These ITD and ILD ranges were chosen to incorporate the physiologically 
relevant range for adult listeners and has also been used in past pediatric studies, including our 
pilot data. Stimuli will be delivered acoustically via ER-3A insert earphones at both a fixed level 
and fixed sensation level across ears, as described above. We will also complete this task using 
both acoustic and electric stimulation with the latter achieved via direct connection to the CI 
sound processor. The lateralization task will gauge intracranial perception of sound location 
allowing us to quantify the full extent of lateralization. This task will utilize a touchscreen tablet 
on which a cartoon image of a head and face is displayed. The participant will touch along a 
visual scale corresponding to the perceptual location of each sound. This procedure has been 
extensively used in both adult and pediatric listeners71,110,111 documenting feasibility of this task 
for our target populations. Each participant will be provided with a period of training to ensure 
familiarization and understanding of the task. We will use the approach of Stecker112 to fit 
psychometric functions relating intracranial position to ITD and ILD via non-linear least squares 
fitting. The relative ITD and ILD slopes will be used to determine the perceptual weighting of 
ITD and ILD cues for each participant. In addition, response-ITD and response-ILD functions 
will be generated to estimate the extent of laterality with one cue fixed (e.g., zero) and with 
coherent ITD and ILD cues.  
AIM 1 expected outcomes and alternative hypotheses: Aim 1 hypotheses are: 1) 
Pediatric CI users will demonstrate an emergence of binaural cue sensitivity following chronic 
EAS use, 2) There will be a relationship between age and cue weighting for lateralization with 
the youngest EAS users assigning greater weight to ILDs—due to immaturities in neural 
synchronization—resulting in a restricted range of laterality, and; 3) The time course of 
pediatric acoustic ITD and ILD development will be correlated with LF acoustic audibility and 
interaural asymmetry. Our hypotheses were built upon the binaural development literature 
showing altered maturation due to both poor audibility and significant interaural 
asymmetry29,113. Alternative hypotheses were based on the notion that EAS creates a 
“problem” introducing interaural differences in neural synchrony due to highly synchronized 
firing in electrically stimulated neurons114 and/or binaurally incongruent cues resulting in 
overrepresentation of laterality to the implanted side. This alternative hypothesis has been 
referred to as “aural preference syndrome” which is well-documented in children with unilateral 
CI115, though never investigated in EAS users. A second alternative hypothesis is that over 
the course of study, both adult and pediatric EAS users will exhibit adaptation to the presence 
of the binaurally incongruous stimulation demonstrating an initial over-representation of the CI 
side, that is ultimately corrected following a period of chronic EAS use—the latter interpretation 
is supported by our preliminary work in adult EAS users9. 
 
AIM 2: Developmental EAS benefit; objective & behavioral measures of binaural 
sensitivity 
Speech recognition in diffuse noise: Speech recognition in diffuse noise will be obtained using 
developmentally appropriate sentence stimuli (AzBio adults, BabyBio children) presented at 67 
dBA with uncorrelated restaurant noise at 62 dB SPL (S0N45-315). Listening conditions tested for 
all participants will include bilateral HA (HA+HA), CI alone (acoustic ears occluded), bimodal 
(CI+HAcontra), as well as EAS (CI+HAbilat). We will assess speech recognition for Aim 2 using the 
3 LF CI cutoffs described in Programming & verification of HA & CI. 

Principal Investigator: Jourdan Holder, AuD PhD 
 
Date: 02/27/2025 
Study Title: Binaural cue sensitivity in children and adults with combined electric and acoustic stimulation 
Institution/Hospital: VUMC 
NCT 
 
Protocol Version #: 3 
 
19 
Protocol Date: 02/27/2025 
Figure 8. Example waveforms 
for the 3 ACC conditions.
time (sec)
amplitude
Spatial release from masking (SRM): SRM will be assessed using laboratory- and clinical-
based measures. Laboratory measures include the Basic English Lexicon (BEL116) sentences 
using one female talker. Maskers will be two different male or female talkers taken from the 
IEEE corpus whose speech samples will either be presented from separate speakers (S0N90&270) 
or concatenated to provide a continuous stream that will be rms-normalized prior to combining 
in a single channel (S0N0, S0N90, S0N270). BEL sentence recognition will be assessed at 0 dB SNR 
for 4 target-masker configurations: S0N0, S0N90, S0N270 and S0N90&270 Clinical measures will use 
the BKB-SIN95 test in a co-located (S0N0) and 3 spatially separated conditions (S0N90, S0N270 and 
S0N90&270)—Figure 5 shows representative data for S0N0 and S0N90,180,270. These configurations 
will reveal SRM due to head shadow (asymmetric masker) or binaural integration (symmetric 
maskers). Speakers are distanced 1 meter from the listener’s head and target speech will be 
fixed at 70 dB SPL. BEL sentences were chosen as this corpus has been used in previous CI 
studies for children of the same age range and 0 dB SNR was based on a previous study 
showing ceiling effects for some children at +5 dB SNR117. BKB-SIN was chosen for its 
normative data to 5 years of age and its pseudoadaptive design which avoids ceiling effects. 
Further, BKB-SIN is commonly used in clinic as it takes just 3 minutes per paired list. We will 
assess performance for CI+HAcontra and CI+HAbilat. Should time allow, we will also obtain a CI-
alone score. 
Spatial discrimination: MAA thresholds will be obtained in an anechoic chamber by 
presenting 2 successive stimuli from different positions in the horizontal plane. The listener will 
indicate whether the 2nd stimulus was to the left or right of the standard. Spatial separation 
between the 70-dB-SPL stimuli will be varied from trial to trial to track 70.7% performance96. 
Noise stimuli will include a BBN and LF noise as described for Aim 1. For the MAA task, 3 
listening conditions will be tested: 1) bilateral HA (HA+HA), 2) bimodal (CI+HAcontra), and EAS 
(CI+HAbilat). Level roving will be applied.  
BMLD & BILD: BMLD and BILD data will be collected via ER-3A earphones for delivery of 
acoustic stimuli. Noise levels will be fixed at equal SPL (EAS: 90 dB SPL; NH: 70 dB SPL). BBN 
and LF noise maskers will be used as described for Aim 1. For BMLD and BILD, the signal will be 
phase correlated (N0S0) or phase inverted (N0S ) relative to the masker. 
The BMLD task will use a 3-interval, forced-choice paradigm with a 2-
down, 1-up adaptive procedure to estimate 70.7% correct performance96. 
BMLD signal frequencies will be 250 and 500 Hz. As described in 
Preliminary Studies, our BILD task uses pediatric-friendly spondees within 
a single interval, 2-down, 1-up adaptive procedure to determine the SNR 
yielding 70.7% correct96.  
ACCIPD, ACCILD, and interaural modulation following response (IM-
FR): CAEPs will be obtained for a 250-Hz carrier that is sinusoidally 
amplitude modulated (SAM), with 100% modulation, at an 83-Hz rate; 
carrier tones are amplitude modulated only so that the change can be 
applied at stimulus nulls, thus avoiding spectral splatter from an 
immediate change to acoustic parameters of an ongoing sound.  The 83-Hz rate allows for 
subcortical envelope following responses (EFRs) to be obtained without significantly impacting 
ACC characteristics118. While the EFR is a secondary interest, the stimuli allow for cortical (ACC) 
and brainstem (EFR) responses to dichotic stimuli to be simultaneously acquired. The SAM tone 
will be 1.6 sec followed by 1.4 sec silence. Stimuli will be presented using electrically shielded 
ER-3A earphones at a level of 90 dB SPL for the EAS listeners and 70 dB SPL for the NH 

Principal Investigator: Jourdan Holder, AuD PhD 
 
Date: 02/27/2025 
Study Title: Binaural cue sensitivity in children and adults with combined electric and acoustic stimulation 
Institution/Hospital: VUMC 
NCT 
 
Protocol Version #: 3 
 
20 
Protocol Date: 02/27/2025 
listeners. Three conditions (Fig. 8) will be tested: 1) Diotic SAM tones, 2) Dichotic-Right SAM 
tones for which the carrier IPD (45, 90, and 180) or ILD (5 dB and 10 dB) will be adjusted 
at 0.8 sec for the stimulus presented to the right ear, 3) Dichotic-Left SAM tones for which the 
carrier phase (IPD) or level (ILD) will be adjusted at 0.8 sec for the stimulus presented to the 
left ear. We recognize that the 90- and 180-degree IPD exceeds the “ecologic range”; however, 
“super ITDs” are important for evaluating coarse ITD sensitivity if fine-grained thresholds are 
not observed. This information will be useful for estimating listener ability to potentially acquire 
and subsequently exploit more fine-grained, ecologically relevant IPD cues. Each condition will 
be presented in a random and counterbalanced order. All AEP testing will be completed within 
approximately 90 minutes in a single-walled, shielded sound booth with a minimum of two 
recording channels: Cz-right ear lobe and Cz-left ear lobe.  
As shown in Figure 6 (Preliminary Studies), robust ACCIPD responses were evoked when 
an IPD change was applied at the midpoint of an ongoing stimulus for NH and EAS listeners 
with physiologically relevant ITD thresholds. As with other objective tests of auditory function, 
time domain analysis may become challenging when responses are absent or have poor 
morphology. This has motivated others85 to adapt the ACC paradigm to make CAEP analysis 
possible in the frequency domain, allowing for more objective and noise-resilient measurements 
(e.g., auditory steady state response). In the interaural modulation following response (IM-FR) 
paradigm, multiple ACCs are evoked in succession by a stimulus that dichotically alternates in 
either IPD (from left-leading or right-leading) or ILD (from left-higher or right-higher) at a fixed 
rate (e.g., 7 Hz). The IM-FR waveform is converted to the frequency domain, and response 
magnitude is assessed at the interaural modulation rate (e.g., 7 Hz). Thus, a sub-aim of this 
work is to parametrically compare time domain ACCs and frequency domain IM-FRs across 
development in NH and EAS groups to assess which tool holds more promise for the primary 
research aims and potentially for clinical application. We plan to use the same IPD and ILD 
manipulations as the ACC method for the IM-FR method. Stimulus length differs between each 
measurement type, but overall testing time will be the same.  
CAEPs will be post-processed and filtered in MATLAB to 
remove eyeblinks and other artifacts. Cleaned responses will be 
analyzed to extract 3 key pieces of information: 1) Normalized 
ACCIPD and ACCILD power: EEG power will be calculated in the 4-
16 Hz frequency band of the 0.8- to 1.2-sec epoch of diotic and 
dichotic conditions (Fig. 9, top). Normalized ACC power will be 
quantified as the ACC power for dichotic conditions divided by the 
power within the same epoch for the diotic (control) condition. 2) 
IM-FR magnitude: IM-FR waveforms will be transformed into the 
frequency domain using fast Fourier transform over the steady-
state portion of the response (0.5-4.5 sec). Spectral magnitude at 
the interaural modulation rate (7 Hz, denoted by asterisk in Fig. 
9) will be used to quantify IPD and ILD sensitivity, respectively. 
3) Neural synchrony: Phase locking values (PLVs119,120) will be extracted from ACC and IM-FR 
waveforms at 83 Hz and 7 Hz, respectively. PLV is a number between 0 and 1 reflecting trial-
by-trial phase coherence of neural activity within specified time-frequency bins. A PLV of 0 
indicates no phase coherence within a bin, whereas a value of 1 indicates complete phase 
coherence. PLV is calculated by epoching continuous EEG trials corresponding to each stimulus 
presentation, creating spectrograms of each trial, and extracting the normalized phase vector at 
DIOTIC (Control)
DICHOTIC
64
32
16
8
4
2
200    600    1000  1400  1800
200    600    1000  1400  1800
Time (ms)
64
32
16
8
4
2
Frequency (Hz)
ACC method
Figure 9: EEG data displayed in the freq-time 
domain via wavelet transform (top); component
spectral magnitude displayed via FFT (bottom).

Principal Investigator: Jourdan Holder, AuD PhD 
 
Date: 02/27/2025 
Study Title: Binaural cue sensitivity in children and adults with combined electric and acoustic stimulation 
Institution/Hospital: VUMC 
NCT 
 
Protocol Version #: 3 
 
21 
Protocol Date: 02/27/2025 
each time-frequency point of the spectrogram. Averaging normalized phase vectors at each 
time-frequency point across all stimulus presentation trials results in the PLV, a proxy for neural 
synchrony. Specifically, 83-Hz PLV provide an index of subcortical neural synchrony, whereas 7-
Hz PLV from IM-FRs provide an index of cortical neural synchrony during IPD or ILD 
manipulations. 
Aim 2 expected outcomes and alternative hypotheses: Aim 2 hypotheses are: 1) 
Children will derive EAS benefit from binaural acoustic hearing for speech in noise, SRM, and 
spatial discrimination, 2) EAS benefit will develop over time for children following a period of 
chronic EAS use (EAS benefit will be mediated by binaural LF information), and 3) there will be 
a relationship between objective estimates of binaural sensitivity and EAS benefit for speech 
recognition and spatial hearing. These hypotheses are built upon a wealth of literature 
demonstrating the importance of access to LF ITD cues for spatial hearing121,122 and the role of 
neural synchrony—estimated electrophysiologically—for ITD coding and perception20,36. An 
alternative hypothesis is that having access to LF ITD cues may not accurately predict EAS 
benefit for spatial hearing tasks, particularly for pediatric EAS users, given the peripheral 
acoustic delays inherent in electric and acoustic hearing123,124; however, we have considerable 
evidence from both the adult EAS literature3–9,16 and from 3 pediatric chronic EAS users 
discussed in Preliminary Studies demonstrating EAS benefit—indicative of binaural cue 
sensitivity—in the free field using clinical HAs and CIs. Thus, it is reasonable to anticipate 
interaural delays imposed for LF binaural acoustic amplification can be overcome with EAS 
experience despite lack of CI/HA synchronization, as evidenced in our preliminary work9. 
 
7.0 
Risks 
 
There are no more than minimal risks for the audiometric testing completed for this study in 
relation to the standard audiometric test battery. There is a risk of loss of confidentiality while 
participating in the research study. All tests will use acoustic stimuli presented in the sound field 
or direct connection to the subject’s cochlear implant sound processor at comfortable levels 
experienced in everyday life. Auditory evoked potentials are also minimal risk and routinely 
completed in both clinical and research environments. There may be unknown or unanticipated 
adverse effects which would be reported to the VUMC IRB within 7 calendar days as described 
below. 
 
8.0 
Reporting of Adverse Events or Unanticipated Problems involving Risk to 
Participants or Others 
 
Review of any unanticipated problems will occur throughout the study. Adverse events will be 
reported to the VUMC Institutional Review Board within 7 calendar days. 
 
 
9.0 
Study Withdrawal/Discontinuation 
 
Participants can withdraw from the study at any time by contacting study personnel.  
 
10.0 Statistical Considerations 
 

Principal Investigator: Jourdan Holder, AuD PhD 
 
Date: 02/27/2025 
Study Title: Binaural cue sensitivity in children and adults with combined electric and acoustic stimulation 
Institution/Hospital: VUMC 
NCT 
 
Protocol Version #: 3 
 
22 
Protocol Date: 02/27/2025 
Statistical analysis will be completed using collected auditory perception data using mixed model 
design (within- and between-subjects analyses). Biostatistician, Dr. Mary Dietrich, is a co-
investigator and will guide preparation and execution of statistical analyses. 
 
 
11.0 Privacy/Confidentiality Issues 
 
All reasonable efforts will be made to keep information collected private and confidential. Each 
individual will be assigned a unique study identifier and the collected information will be de-
identified. Information may be shared with institutional and/or governmental authorities, such 
as the Vanderbilt University Medical Center Institutional Review Board as indicated. 
 
12.0 Follow-up and Record Retention 
 
The duration of the study will be 6 years.  
 
13.0   Summarized study protocol 
 
 
Summary of assessment battery defined by current clinical 
practice:  
 
Tasks to be administered at baseline visit only 
• 
KBIT-2 
• 
MoCA 
 
Tasks to be administered at each study visit 
CNC monosyllabic word recognition 
• 
CI ear (in EAS condition—CI + ipsilateral acoustic component) 
• 
Bilateral best-aided (CI + bilateral HAs) 
AzBio or BabyBio sentence recognition at +5 dB SNR S0N0 
• 
CI ear (in EAS condition—CI + ipsilateral acoustic component) 
• 
Bilateral best-aided (CI + bilateral HAs) 
BKB-SIN S0N0 
• 
CI ear (in EAS condition—CI + ipsilateral acoustic component) 
• 
Bilateral best-aided (CI + bilateral HAs) 
SSQ or SSQ-parent  
 
Unaided, pure-tone audiometry in implanted ear via insert earphone 
• 
125-8000 Hz 
• 
AC & BC 
 
CI-aided, pure-tone audiometry in sound field with FM tones and acoustic ears occluded via EAR 
foam plug 
• 
If CI-aided thresholds are in the range of 20-30 dB HL, no further programming is 
needed. 

Principal Investigator: Jourdan Holder, AuD PhD 
 
Date: 02/27/2025 
Study Title: Binaural cue sensitivity in children and adults with combined electric and acoustic stimulation 
Institution/Hospital: VUMC 
NCT 
 
Protocol Version #: 3 
 
23 
Protocol Date: 02/27/2025 
• 
If CI-aided thresholds are lower or higher than this range, CI programming is required.  
 
HA/acoustic component verification using audioscan verifit to DSL-Child or NAL-NL1 for pediatric 
and adult EAS participants, respectively.  
• 
SII at 50, 60, and 70 dB SPL 
• 
If targets are poorly met, re-program HA(s) and re-verify. 
 
Tasks to be administered at baseline and in 1-year increments 
• 
Numbers reversed subtest on Woodcock-Johnson IV (WJ-IV) 
• 
Receptive One-Word Picture Vocabulary Test-4 (ROWPVT-4104)  
• 
Clinical Evaluation of Language Fundamentals (CELF-5) 
• 
Unaided audiometry for non-implanted ear (EAS group only) 
 
 
AIM 1: Summary of assessment battery  
 
ITD & ILD thresholds and cue weighting tasks—completed at baseline and all 
subsequent study visits 
• Acoustic only hearing using insert earphones 
• Acoustic plus electric using insert earphones and direct audio input to CI 
o For participants without a CI, acoustic-only ITD & ILD thresholds will be 
assessed 
 
 
AIM 2: Summary of assessment battery  
 
Spatial release from masking (SRM)—baseline and all subsequent visits 
 
BEL sentence recognition  
Test conditions include: 1) CI ear (CI+acoustic component—optional), 2) bimodal 
(CI+contralateral HA), and 3) best-aided EAS (CI + bilateral HAs) 
• 
BEL sentences presented at 70 dB SPL (A weighting) at 0 dB SNR for the following 4 
target-masker configurations:  
o S0N0 
o S0N90 
o S0N270 
o S0N90&270 
 
BKB-SIN  
Test conditions include: 1) CI ear (CI+acoustic component—optional), 2) bimodal 
(CI+contralateral HA), and 3) best-aided EAS (CI + bilateral HAs) 
• 
BEL sentences presented at 70 dB SPL (A weighting) at 0 dB SNR for the following 4 
target-masker configurations:  

Principal Investigator: Jourdan Holder, AuD PhD 
 
Date: 02/27/2025 
Study Title: Binaural cue sensitivity in children and adults with combined electric and acoustic stimulation 
Institution/Hospital: VUMC 
NCT 
 
Protocol Version #: 3 
 
24 
Protocol Date: 02/27/2025 
o S0N0 
o S0N90 
o S0N270 
o S0N90&270 
 
 
Minimum audible angle (MAA) in the anechoic chamber—baseline and all 
subsequent visits 
BBN and LF noise bursts will be presented at 70 dB SPL (A weighted) with level roving (+/-7 
dB) using the anechoic chamber. The following listening conditions will be tested:  
• 
bilateral HA (HA+HA) 
• 
bimodal (CI+HAcontra) 
• 
EAS (CI+HAbilat) 
 
Binaural masking level difference (BMLD) and binaural intelligibility level difference 
(BILD) (baseline and all subsequent visits) 
BMLD and BILD data will be measured via ER-3A earphones for delivery of acoustic stimuli. BBN 
and LF noise will be presented as follows:  
EAS participants:  
• 
90 dB SPL 
• 
phase correlated (N0S0) or phase inverted (N0S) 
NH participants:  
• 
70 dB SPL 
• 
phase correlated (N0S0) or phase inverted (N0S) 
 
Auditory evoked potentials (AEPs) including ACCIPD, ACCILD, and interaural 
modulation following response (IM-FR) (baseline and all subsequent visits) 
 
A 250-Hz tone (1.6 sec) will be sinusoidally amplitude modulated at 83 Hz and presented using 
electrically shielded ER-3A earphones at the following levels: 
 
EAS participants 
• 
90 dB SPL in both ears 
NH participants 
• 
70 dB SPL in both ears 
 
The following AEP conditions will be completed at each study visits:  
• 
Diotic SAM tone 
• 
Dichotic-Right SAM tones for which the carrier IPD (45, 90, and 180) or ILD (5 dB 
and 10 dB) will be adjusted at 0.8 sec for the stimulus presented to the right ear 
• 
Dichotic-Left SAM tones for which the carrier phase (IPD) or level (ILD) will be adjusted 
at 0.8 sec for the stimulus presented to the left ear.