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.

Public responses to water reuse - Understanding the evidence.

Over the years, much research has attempted to unpack what drives public responses to water reuse, using a variety of approaches. A large amount of this work was captured by an initial review that covered research undertaken up to the early 2000s (Hartley, 2006). This paper showcases post-millennium evidence and thinking around public responses to water reuse, and highlights the novel insights and shifts in emphasis that have occurred in the field. Our analysis is structured around four broad, and highly interrelated, strands of thinking: 1) work focused on identifying the range of factors that influence public reactions to the concept of water reuse, and broadly looking for associations between different factors; 2) more specific approaches rooted in the socio-psychological modelling techniques; 3) work with a particular focus on understanding the influences of trust, risk perceptions and affective (emotional) reactions; and 4) work utilising social constructivist perspectives and socio-technical systems theory to frame responses to water reuse. Some of the most significant advancements in thinking in this field stem from the increasingly sophisticated understanding of the 'yuck factor' and the role of such pre-cognitive affective reactions. These are deeply entrenched within individuals, but are also linked with wider societal processes and social representations. Work in this area suggests that responses to reuse are situated within an overall process of technological 'legitimation'. These emerging insights should help stimulate some novel thinking around approaches to public engagement for water reuse.

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.

Neuropsychological profile in adults with neurofibromatosis type 1 compared to a control group.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a common inherited autosomal dominant condition, characterised by multiple café-au-lait macules, axillary and/or inguinal freckling, iris Lisch nodules and tumours of the nervous system such as neurofibromas and optic pathway gliomas. At the same time, NF1 is frequently associated with intellectual disabilities across several neuropsychological domains. Existing neuropsychological data in NF1 adults are limited and sometimes contradictory. Moreover, most studies use a non-IQ-controlled norm group for comparison. This study sought to investigate specific neuropsychological characteristics in intellectual abilities unrelated to the global intellectual capacity. METHOD: Twenty NF1 adults and an IQ-, age- and gender-matched control group completed a comprehensive neuropsychological test battery composed of specific cognitive tests investigating visual-spatial abilities and memory, auditory memory, selective and sustained attention and executive functioning. A short version of the Wechsler Adult Intelligence Scale - III was also administered to both groups. RESULTS: Norm comparison showed that both groups perform poorly on most neuropsychological functions, except for sustained attention. However, comparison with the IQ-matched control group showed significantly lower scores on visual-spatial abilities and memory, on auditory working memory and on tests for cognitive flexibility in NF1 adults. Nevertheless, as the significant difference in average estimated IQ score between the NF1 group and the selected control group almost reaches the 5% significance level, further analysis is needed to include IQ as a covariate. Eventually, problems in visual-spatial skills and auditory long-term memory seem to be specific NF1-related deficits, while problems in attention and executive functioning are particularly related to their general lowered intellectual abilities. CONCLUSION: Taking into account that primary visual perception problems could be part of a more general central coherence deficit while interpreting auditory memory problems as possibly related to deficits in language use and comprehension, this idea also fits with the observation of several problems in social information processing and functioning of NF1 persons.

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.

Newborn hearing screening and cochlear implantation: impact on spoken language development.

OBJECTIVES: This study retrospectively evaluates the effect of newborn hearing screening on age at diagnosis, age at cochlear implantation and spoken language development in severely hearing-impaired children. METHODS: Age at diagnosis, age at cochlear implantation and language development were evaluated in a group of early screened (n = 149) and a group of late screened (n = 139) severely hearing-impaired children. Language outcomes were quantified as language quotients (LQs) on the Reynell Developmental Language Scales and Schlichting Expressive Language Test at 1,2, and 3 years after cochlear implantation. RESULTS: Early screened children were significantly younger than late screened children at the time of hearing loss diagnosis and cochlear implantation. Furthermore, early screening was associated with better receptive and expressive spoken language skills after cochlear implantation. CONCLUSION: The results of this retrospective study indicate that the newborn hearing screening program in Flanders and The Netherlands resulted in earlier intervention in deaf children, which beneficially influenced spoken language development.

Microduplication 22q11.2: a description of the clinical, developmental and behavioral characteristics during childhood.

Microduplication 22q11.2 is a recently discovered genomic disorder. So far, targeted research on the cognitive and behavioral characteristics of individuals with this microduplication is limited. Therefore, 11 Flemish children (3-13 years old) with a microduplication 22q 1.2 were investigated in order to describe their clinical, developmental and behavioral characteristics. We measured their general intelligence, visual-motor capacities, attention, behavioral problems and characteristics of autism. In addition, there was an interview with the parents on developmental history and we reviewed available information from other specialists. The results show that the cognitive and behavioral phenotype of the children with microduplication 22q.11.2 is very wide and heterogeneous. Some of the children have a cognitively nearly normal development whereas others are more severely affected. All children had some degree of developmental delay and some of them have an intellectual disability. The most common clinical features include congenital malformations such as heart defects and cleft lip, feeding problems, hearing impairment and facial dysmorphism. The most common non-medical problems are learning difficulties, motor impairment, attention deficits, social problems and behavioral problems. There is no correlation between the size of the duplication and the phenotype.

Neuropsychopathology in 7 Patients with the 22q13 Deletion Syndrome: Presence of Bipolar Disorder and Progressive Loss of Skills.

The 22q13 deletion syndrome is characterised by intellectual disability (ID), delayed or absent speech, autistic-like behaviour and minor, nonspecific dysmorphic features. The deletion of the SHANK3 gene is thought to be responsible for these features. In this study, the clinical data of 7 patients with the 22q13 deletion syndrome are presented, obtained by clinical genetic examination, direct behavioural observation and by interview of family members and/or caregivers, complemented by behavioural questionnaires. The specific focus was on behaviour, psychopathology and the level of functioning during life course in order to determine common features that might contribute to the delineation of the syndrome. Major findings were a high incidence of psychiatric disorders, more in particular bipolar disorder (BPD) and attention deficit hyperactivity disorder (ADHD), and a sudden deterioration after acute events, in addition to a progressive loss of skills over years. Therefore, a deletion of SHANK3 may result in a dysfunctional nervous system, more susceptible to developmental problems and psychiatric disorders on the one hand, less able to recuperate after psychiatric and somatic events, and more vulnerable to degeneration at long term on the other hand. These results are exploratory and need to be confirmed in a larger sample.

Difficult prenatal diagnosis: fetal coarctation.

The prenatal diagnosis of fetal coarctation is still challenging. It is mainly suspected by ventricular disproportion (smaller left ventricle than right ventricle). The sensitivity of ventricular discrepancy is however moderate for the diagnosis of coarctation and there is a high false positive rate. Prenatal diagnosis of coarctation is important because the delivery can be arranged in a centre with a pediatric cardiac intensive careand this reduces postnatal complications and longterm morbidity. For many years the prenatal diagnosis of coarctation has been investigated to improve specificity and sensitivity by several of measurements. This article reviews all relevant articles from 2000 until 2011 searching pubmed and the reference list of interesting articles. An overview of specific measurements and techniques that can improve the diagnosis of coarctation has been made, such as the isthmus diameter, ductal diameter, isthmus/ductal ratio, z-scores derived from measurements of the distal aortic isthmus and arterial duct, the presence of a shelf andisthmal flow disturbance. Also 3-dimensional (3D) and 4-dimensional (4D) imaging with or without STIC has been -suggested to be used as newer techniques to improve diagnosis of coarctation in fetal life. Although more methods regarding prenatal diagnosis of coarctationare being investigated, the ultrasound specialist remains challenged to correctly diagnose this cardiac anomaly in prenatal life.