Evaluation of Two Spectro-Temporal Ripple Tests and Their Relation to the Matrix Speech-in-Noise Sentence Test in Cochlear Implant Recipients.

OBJECTIVES: Spectro-temporal ripple tests are commonly used in cochlear implant (CI) research as language-independent indicators of speech recognition (in noise) or as stand-alone tests. Test-retest reliability of these tests has been scarcely documented. We evaluated the test-retest reliability of spectral-temporally modulated ripple test (SMRT) and spectro-temporal ripple for investigating processor effectiveness (STRIPES) and correlated their findings to the Dutch/Flemish Matrix speech-in-noise sentence test (MST) in CI recipients. This is the first time spectro-temporal ripple tests are correlated to an MST. DESIGN: Take-home data from 15 participants over 2 test days were analyzed. Participants were fitted with their clinical speech encoding strategy (Advanced Bionics HiRes Optima) or a 14-channel non-steered monopolar strategy. Test-retest reliability was calculated through intraclass correlation coefficients and visualized through Bland Altman plots. Association of the spectro-temporal ripple tests with the MST was evaluated through linear regression analysis. RESULTS: The SMRT and STRIPES possessed a similarly rated "good" test-retest reliability (SMRT: ICC = 0.81, confidence interval = 0.67 to 0.92; STRIPES: ICC = 0.87, confidence interval = 0.76 to 0.95) and an identical linear relationship to speech recognition in noise (SMRT: R2 = 0.28, p = 0.04; STRIPES: R2 = 0.28, p = 0.04). Both tests revealed a stable variability between session 1 and 2 outcome scores on Bland Altman plots. CONCLUSION: On the basis of our data, both spectro-temporal ripple tests possess similar test-retest reliability and a similar association with the MST. The SMRT and STRIPES can therefore both be used equally well as a quick indicator of across-listener differences in speech recognition in noise in CI recipients.

Benefit of sequential bilateral cochlear implantation in children between 5 to 18 years old: A prospective cohort study.

OBJECTIVE: To determine the benefit of sequential cochlear implantation after a long inter-implantation interval in children with bilateral deafness receiving their second implant between 5 and 18 years of age. STUDY DESIGN: Prospective cohort-study. SETTING: Tertiary multicenter. PATIENTS: 85 children with bilateral deafness and unilateral implantation receiving a contralateral cochlear implant at the age of 5 to 18 years. METHOD: The primary outcomes were speech recognition in quiet and noise (CVC) scores. The secondary outcomes were language outcomes and subjective hearing abilities, all measured before and 12 months after sequential bilateral cochlear implantation. Medians of the paired data were compared using the Wilcoxon signed-rank test. Univariable linear regression analyses was used to analyze associations between variables and performance outcomes. RESULTS: A significant benefit was found for speech recognition in quiet (96% [89-98] vs 91% [85-96]; p < 0.01) and noise (65% [57-75] vs 54% [47-71]; p = 0.01) in the bilateral CI condition compared to unilateral (n = 75, excluded 10 non-users). No benefit was seen for language outcomes. The subjective sound quality score was statistically significant higher in bilateral compared to the unilateral CI condition. Pre-operative residual hearing level in the ear of the second implant, the inter-implant interval and age at time of second implantation was not significantly associated with performance scores. CONCLUSION: After 12 months of use, sequential bilateral cochlear implantation showed improved speech perception in quiet and noise and improved subjective sound quality outcomes in children despite a great inter-implantation interval (median of 8 years [range 1-16 years]).

Short and long-term adaptation in the auditory nerve stimulated with high-rate electrical pulse trains are better described by a power law.

Despite the introduction of many new sound-coding strategies speech perception outcomes in cochlear implant listeners have leveled off. Computer models may help speed up the evaluation of new sound-coding strategies, but most existing models of auditory nerve responses to electrical stimulation include limited temporal detail, as the effects of longer stimulation, such as adaptation, are not well-studied. Measured neural responses to stimulation with both short (400 ms) and long (10 min) duration high-rate (5kpps) pulse trains were compared in terms of spike rate and vector strength (VS) with model outcomes obtained with different forms of adaptation. A previously published model combining biophysical and phenomenological approaches was adjusted with adaptation modeled as a single decaying exponent, multiple exponents and a power law. For long duration data, power law adaptation by far outperforms the single exponent model, especially when it is optimized per fiber. For short duration data, all tested models performed comparably well, with slightly better performance of the single exponent model for VS and of the power law model for the spike rates. The power law parameter sets obtained when fitted to the long duration data also yielded adequate predictions for short duration stimulation, and vice versa. The power law function can be approximated with multiple exponents, which is physiologically more viable. The number of required exponents depends on the duration of simulation; the 400 ms data was well-replicated by two exponents (23 and 212 ms), whereas the 10-minute data required at least seven exponents (ranging from 4 ms to 600 s). Adaptation of the auditory nerve to high-rate electrical stimulation can best be described by a power-law or a sum of exponents. This gives an adequate fit for both short and long duration stimuli, such as CI speech segments.

The Temporal Fine Structure of Background Noise Determines the Benefit of Bimodal Hearing for Recognizing Speech.

Cochlear implant (CI) users have more difficulty understanding speech in temporally modulated noise than in steady-state (SS) noise. This is thought to be caused by the limited low-frequency information that CIs provide, as well as by the envelope coding in CIs that discards the temporal fine structure (TFS). Contralateral amplification with a hearing aid, referred to as bimodal hearing, can potentially provide CI users with TFS cues to complement the envelope cues provided by the CI signal. In this study, we investigated whether the use of a CI alone provides access to only envelope cues and whether acoustic amplification can provide additional access to TFS cues. To this end, we evaluated speech recognition in bimodal listeners, using SS noise and two amplitude-modulated noise types, namely babble noise and amplitude-modulated steady-state (AMSS) noise. We hypothesized that speech recognition in noise depends on the envelope of the noise, but not on its TFS when listening with a CI. Secondly, we hypothesized that the amount of benefit gained by the addition of a contralateral hearing aid depends on both the envelope and TFS of the noise. The two amplitude-modulated noise types decreased speech recognition more effectively than SS noise. Against expectations, however, we found that babble noise decreased speech recognition more effectively than AMSS noise in the CI-only condition. Therefore, we rejected our hypothesis that TFS is not available to CI users. In line with expectations, we found that the bimodal benefit was highest in babble noise. However, there was no significant difference between the bimodal benefit obtained in SS and AMSS noise. Our results suggest that a CI alone can provide TFS cues and that bimodal benefits in noise depend on TFS, but not on the envelope of the noise.

Effect of neural adaptation and degeneration on pulse-train ECAPs: A model study.

Electrically evoked compound action potentials (eCAPs) are measurements of the auditory nerve's response to electrical stimulation. ECAP amplitudes during pulse trains can exhibit temporal alternations. The magnitude of this alternation tends to diminish over time during the stimulus. How this pattern relates to the temporal behavior of nerve fibers is not known. We hypothesized that the stochasticity, refractoriness, adaptation of the threshold and spike-times influence pulse-train eCAP responses. Thirty thousand auditory nerve fibers were modeled in a three-dimensional cochlear model incorporating pulse-shape effects, pulse-history effects, and stochasticity in the individual neural responses. ECAPs in response to pulse trains of different rates and amplitudes were modeled for fibers with different stochastic properties (by variation of the relative spread) and different temporal properties (by variation of the refractory periods, adaptation and latency). The model predicts alternation of peak amplitudes similar to available human data. In addition, the peak alternation was affected by changing the refractoriness, adaptation, and relative spread of auditory nerve fibers. As these parameters are related to factors such as the duration of deafness and neural survival, this study suggests that the eCAP pattern in response to pulse trains could be used to assess the underlying temporal and stochastic behavior of the auditory nerve. As these properties affect the nerve's response to pulse trains, they are of uttermost importance to sound perception with cochlear implants.

Modeled auditory nerve responses to amplitude modulated cochlear implant stimulation.

Cochlear implants encode speech information by stimulating the auditory nerve with amplitude-modulated pulse trains. A computer model of the auditory nerve's response to electrical stimulation can be used to evaluate different approaches to improving CI patients' perception. In this paper a computationally efficient stochastic and adaptive auditory nerve model was used to investigate full nerve responses to amplitude-modulated electrical pulse trains. The model was validated for nerve responses to AM pulse trains via comparison with animal data. The influence of different parameters, such as adaptation and stochasticity, on long-term adaptation and modulation-following behavior was investigated. Responses to pulse trains with different pulse amplitudes, amplitude modulation frequencies, and modulation depths were modeled. Rate responses as well as period histograms, Vector Strength and the fundamental frequency were characterized in different time bins. The response alterations, including frequency following behavior, observed over the stimulus duration were similar to those seen in animal experiments. The tested model can be used to predict complete nerve responses to arbitrary input, and thus to different sound coding strategies.

A fast, stochastic, and adaptive model of auditory nerve responses to cochlear implant stimulation.

Cochlear implants (CIs) rehabilitate hearing impairment through direct electrical stimulation of the auditory nerve. New stimulation strategies can be evaluated using computational models. In this study, a computationally efficient model that accurately predicts auditory nerve responses to CI pulse train input was developed. A three-dimensional volume conduction and active nerve model developed at Leiden University Medical Center was extended with stochasticity, adaptation, and accommodation. This complete model includes spatial and temporal characteristics of both the cochlea and the auditory nerve. The model was validated by comparison with experimentally measured single fiber action potential responses to pulse trains published in the literature. The effects of pulse rate and pulse amplitude on spiking patterns were investigated. The modeled neural responses to CI stimulation were very similar to the single fiber action potential measurements in animal experiments. The model's responses to pulse train stimulation with respect to spatial location were also investigated. Adaptation was stronger at the borders of the stimulated area than in the center. By combining spatial details with long-term temporal components and a broad implementation of stochasticity a comprehensive model was developed that was validated for long duration electric stimulation of a wide range of pulse rates and amplitudes. The model can be used to evaluate auditory nerve responses to cochlear implant sound coding strategies.

Benefit of contralateral routing of signals for unilateral cochlear implant users.

One way to improve speech understanding in noise for HI with a unilateral hearing loss is by contralateral routing of signals (CROS). Such a CROS-system captures sounds with an additional microphone at the worst hearing ear and transmits these to the better one. The better ear is then provided with a mix of signals originating from both ears. The goal of this study is to quantify the effect of a CROS-system on speech reception thresholds (SRTs) with unilaterally implanted CI-users in diffuse and directional noise as a function of speaker location. Listening tests are performed and an accurate directional intelligibly model is proposed used for further analysis. In diffuse noise it is concluded that the use of a CROS system results in a maximum gain in SRT of 7.9 dB when speech comes from the CROS side compared to a maximum loss in SRT of 2.1 dB when speech comes from the implanted side. In the case of directional noise, the effect of the CROS is symmetric and the maximum loss or gain in SRT was around 9 dB. The study therefore shows a clear potential of using the CROS system in diffuse noise.

Human Dermal Fibroblasts Demonstrate Positive Immunostaining for Neuron- and Glia- Specific Proteins.

In stem cell cultures from adult human tissue, undesirable contamination with fibroblasts is frequently present. The presence of fibroblasts obscures the actual number of stem cells and may result in extracellular matrix production after transplantation. Identification of fibroblasts is difficult because of the lack of specific fibroblast markers. In our laboratory, we isolate and expand neural-crest-derived stem cells from human hair follicle bulges and investigate their potential to differentiate into neural cells. To establish cellular identities, we perform immunohistochemistry with antibodies specific for glial and neuronal markers, and use fibroblasts as negative control. We frequently observe that human adult dermal fibroblasts also express some glial and neuronal markers. In this study, we have sought to determine whether our observations represent actual expression of these markers or result from cross-reactivity. Immunohistochemistry was performed on human adult dermal fibroblasts using acknowledged glial and neuronal antibodies followed by verification of the data using RT-qPCR. Human adult dermal fibroblasts showed expression of the glia-specific markers SOX9, glial fibrillary acidic protein and EGR2 (KROX20) as well as for the neuron-specific marker class III ß-tubulin, both at the protein and mRNA level. Furthermore, human adult dermal fibroblasts showed false-positive immunostaining for S100ß and GAP43 and to a lower extent for OCT6. Our results indicate that immunophenotyping as a tool to determine cellular identity is not as reliable as generally assumed, especially since human adult dermal fibroblasts may be mistaken for neural cells, indicating that the ultimate proof of glial or neuronal identity can only be provided by their functionality.

Hair follicle bulge cultures yield class III ß-tubulin-positive melanoglial cells.

Class III ß-tubulin (TUBB3)-positive cells from the hair follicle bulge are thought to be neuronal cells derived from a local neural crest stem cell. However, TUBB3 has recently been shown to be expressed in the melanocytic lineage. To evaluate the neural-crest-associated immunophenotype of TUBB3-positive cells from hair follicle bulge explants, we dissected hair follicle bulges out from mouse whisker pads and cultured for 1 month and assessed outgrowing cells by means of immunocytochemistry using the biomarkers TUBB3, nestin, NGFR, SOX9, TYRP1 and laminin. Large amounts of TUBB3-positive cells could be cultured that co-expressed nestin, NGFR, SOX9 and, to a lesser degree, TYRP1, matching a melanoglial phenotype. In addition, a small population of TUBB3-negative but laminin-positive cells was found, which presumably are of glial origin. It can be concluded that cells of melanoglial origin can easily be obtained from hair follicle bulge explants. These cells may be of use in experimental animal or human disease and wound healing models. Notably, the TUBB3-positive cells are of melanoglial rather than neuronal origin.

Visualization of human inner ear anatomy with high-resolution MR imaging at 7T: initial clinical assessment.

BACKGROUND AND PURPOSE: In many centers, MR imaging of the inner ear and auditory pathway performed on 1.5T or 3T systems is part of the preoperative work-up of cochlear implants. We investigated the applicability of clinical inner ear MR imaging at 7T and compared the visibility of inner ear structures and nerves within the internal auditory canal with images acquired at 3T. MATERIALS AND METHODS: Thirteen patients with sensorineural hearing loss eligible for cochlear implantation underwent examinations on 3T and 7T scanners. Two experienced head and neck radiologists evaluated the 52 inner ear datasets. Twenty-four anatomic structures of the inner ear and 1 overall score for image quality were assessed by using a 4-point grading scale for the degree of visibility. RESULTS: The visibility of 11 of the 24 anatomic structures was rated higher on the 7T images. There was no significant difference in the visibility of 13 anatomic structures and the overall quality rating. A higher incidence of artifacts was observed in the 7T images. CONCLUSIONS: The gain in SNR at 7T yielded a more detailed visualization of many anatomic structures, especially delicate ones, despite the challenges accompanying MR imaging at a high magnetic field.

An improved system approach towards future cochlear implants.

Cochlear implants (CIs) have been used for many years to restore hearing for deaf patients. Unfortunately, today's CIs are still bulky devices and uncomfortable to wear. In this paper we present three innovations that ultimately should pave the way to a fully implantable bionic ear. First a microfabrication process used to fabricate the polymer metal microelectrode array for auditory nerve stimulation is discussed. Subsequently, a compact biphasic programmable stimulator chip to be used along with this electrode array is presented. By using a double loop feedback circuit topology, the circuit provides a precise stimulation current while requiring only little voltage headroom. The resulting low power consumption and reduced chip area allow for integration of the electronic circuitry onto the electrode array. Finally, as reliability and data transmission rate are two of the most critical issues in CI devices, we propose a software method to improve both data rate and reliability of transmitting digital data from the external part of the CI to the internal part with negligible power consumption.

National study of newborn hearing screening: programme sensitivity and characteristics of undetected children.

UNLABELLED: The success of universal newborn hearing screening (UNHS) programmes is usually evaluated by determining the effect of the early detection of hearing loss on developmental outcome. However, in practice, these programmes do not detect all children with permanent childhood hearing impairment. In this study we determine the sensitivity of the current UNHS programme and analyse the characteristics of the children not detected by UNHS. We performed a nationwide, population-based, retrospective follow-up study in The Netherlands. All children born in 2003-05 and screened in a hearing screening programme (well babies and neonatal intensive care (NICU) graduates) were included for study. The main outcome measure was the sensitivity of the UNHS programme (based on the proportion of children known to have a permanent childhood hearing impairment in 2008 who were identified by UNHS). We also evaluated age at diagnosis, severity, and aetiology of hearing impairment in the children not detected by UNHS. We found that the sensitivity of the current UNHS programme was 0.83 (0.79 for well babies and 0.96 for NICU graduates). Permanent childhood hearing impairment was confirmed before 36 months of age in 96% of the study cohort. Of the children unidentified by the UNHS, > 50% had moderate hearing loss. No predominant cause of hearing impairment was found in these children. CONCLUSION: Our current UNHS programme identified the majority of children with a permanent hearing impairment of congenital cause.

Stimulus level effects on neural excitation and eCAP amplitude.

The common assumption that the electrically evoked compound action potential (eCAP) has a linear relationship with the number of excited nerve fibres is derived from the acoustical unitary response concept. This study tests the validity of this hypothesis for electrical stimulation. Five guinea pigs were implanted with the tip of a human HiFocus electrode. eCAPs were measured with the forward masking paradigm, using anodic- and cathodic-leading biphasic current pulses and the inter-pulse interval was varied. Masker and probe amplitudes were varied either individually or simultaneously. Surprisingly, at high levels decreasing eCAP amplitudes were measured with increasing stimulus current. In search for an explanation, the experimental conditions were implemented in our 3D computational model of the implanted guinea pig cochlea to perform a functional comparison. In the final experiment, with fixed inter-pulse interval (IPI) and anodic-leading pulses, increasing stimulus currents showed growing numbers of excited nerve fibres and decreasing eCAP amplitudes at high levels, again. While simulating the relative contribution of single fibres to the overall eCAP, an explanation for this could be found in a waveform change in the modelled single fibre action potentials at high levels. We conclude that highly stimulated nerve fibres have another contribution to the eCAP response than lower stimulated fibres, which leads to a reduction of the eCAP amplitude at high levels.

Bilateral versus unilateral cochlear implantation in young children.

OBJECTIVES: To compare the preverbal communication skills of two groups of young implanted children: those with unilateral implantation and those with bilateral implantation. MATERIAL AND METHODS: The study assessed 69 children: 42 unilaterally and 27 bilaterally implanted with age at implantation less than 3 years. The preverbal skills of these children were measured before and 1 year after implantation, using Tait Video Analysis that has been found able to predict later speech outcomes in young implanted children. RESULTS: Before implantation there was no significant difference between the unilateral group and the bilateral group. There was still no difference at 12 months following implantation where vocal autonomy is concerned, but a strongly significant difference between the groups for vocal turn-taking and non-looking vocal turns, the bilateral group outperforming the unilateral group. Regarding gestural turn-taking and gestural autonomy, there was a strongly significant difference between the two groups at the 12 month interval, and also a difference before implantation for gestural autonomy, the unilateral group having the higher scores. Multiple regression of non-looking vocal turns revealed that 1 year following implantation, bilateral implantation contributed to 51% of the variance (p<0.0001), after controlling for the influence of age at implantation and length of deafness which did not reach statistical significance. CONCLUSIONS: Profoundly deaf bilaterally implanted children are significantly more likely to use vocalisation to communicate, and to use audition when interacting vocally with an adult, compared with unilaterally implanted children. These results are independent of age at implantation and length of deafness.

DECIBEL study: Congenital cytomegalovirus infection in young children with permanent bilateral hearing impairment in the Netherlands.

BACKGROUND: A significant number of asymptomatic newborns infected with congenital cytomegalovirus (CMV) will present with permanent childhood hearing impairment (PCHI) during early childhood. OBJECTIVES: To investigate the role of congenital CMV infection in causing PCHI in the Netherlands, and assess the efficacy of two different hearing screening strategies and the developmental outcome following each strategy. STUDY DESIGN: We included 192 children with PCHI at the age of 3-5 years, who were offered hearing screening in their first year of life. Dried blood spots from 171 children were available for CMV detection using real-time PCR. The results of eight previously tested samples were also available. Clinical baseline characteristics were collected from medical records and the Child Development Inventory was used to investigate the developmental outcome. RESULTS: The rate of congenital CMV among the 179 children was 8% (14/179) and 23% (9/39) among children with profound PCHI. Two of eight CMV-positive children with PCHI at the age of 3-5 years had passed the newborn hearing screening (NHS) test. Developmental outcome measures showed a significantly greater delay in language comprehension in children with both PCHI and congenital CMV infection (the largest in symptomatic children) than in the children with PCHI without congenital CMV infection. CONCLUSIONS: Congenital CMV infection is important in the etiology of PCHI. Universal NHS is not a guarantee of normal hearing and development in childhood for children with congenital CMV infection. This is a problem which might be solved by universal congenital CMV screening.

Evaluation of 4 multisection CT systems in postoperative imaging of a cochlear implant: a human cadaver and phantom study.

BACKGROUND AND PURPOSE: Postoperative imaging of cochlear implants (CIs) needs to provide detailed information on localization of the electrode array. We evaluated visualization of a HiFocus1J array and accuracy of measurements of electrode positions for acquisitions with 64-section CT scanners of 4 major CT systems (Toshiba Aquilion-64, Philips Brilliance-64, GE LightSpeed-64, and Siemens Sensation-64). MATERIALS AND METHODS: An implanted human cadaver temporal bone, a polymethylmethacrylate (PMMA) phantom containing a CI, and a point spread function (PSF) phantom were scanned. In the human cadaver temporal bone, the visibility of cochlear structures and electrode array were assessed by using a visual analog scale (VAS). Statistical analysis was performed with a paired 2-tailed Student t test with significant level set to .008 after Bonferroni correction. Distinction of individual electrode contacts was quantitatively evaluated. Quantitative assessment of electrode contact positions was achieved with the PMMA phantom by measurement of the displacement. In addition, PSF was measured to evaluate spatial resolution performance of the CT scanners. RESULTS: VAS scores were significantly lower for Brilliance-64 and LightSpeed-64 compared with Aquilion-64 and Sensation-64. Displacement of electrode contacts ranged from 0.05 to 0.14 mm on Aquilion-64, 0.07 to 0.16 mm on Brilliance-64, 0.07 to 0.61 mm on LightSpeed-64, and 0.03 to 0.13 mm on Sensation-64. PSF measurements show an in-plane and longitudinal resolution varying from 0.48 to 0.68 mm and 0.70 to 0.98 mm, respectively, over the 4 scanners. CONCLUSION: According to PSF results, electrode contacts of the studied CI can be visualized separately on all of the studied scanners unless curvature causes intercontact spacing narrowing. Assessment of visibility of CI and electrode contact positions, however, varies between scanners.

[Permanent hearing loss in the prelingual phase in children with a non-aberrant neonatal hearing screening result]. / Permanent gehoorverlies in de prelinguale fase bij kinderen met een niet-afwijkende uitslag bij neonatale gehoorscreening.

--Neonatal hearing screening is fully implemented in the Netherlands since June 2006 using otoacoustic emissions (OAE) and automated auditory brainstem response (AABR) technology. --A normal neonatal hearing screening result unfortunately does not guarantee childhood normal hearing. Hearing loss may not become manifest until after the neonatal period. --Hearing loss at a later stage may be classified in three categories: (a) delayed onset hearing loss which occurs when the cause of the hearing loss is present at birth but the hearing loss itself becomes detectable at a later stage; (b) progressive hearing loss in which a very slight hearing loss may be present at birth but is not yet detectable and the hearing loss becomes progressively more severe; and (c) acquired hearing loss that results from a number of external factors, such as meningitis, ototoxic drugs, neonatal hyperbilirubinaemia necessitating an exchange transfusion, and trauma. --Neonatal hearing screening can result in detection of moderate to profound permanent hearing loss at an early age when therapeutic options may have maximum effect. However, even after this period, constant vigilance is necessary to detect permanent hearing loss in young children, especially during the prelingual period.