Effects of the BalanCI on Working Memory and Balance in Children and Young Adults With Cochleovestibular Dysfunction.

OBJECTIVES: This study aimed to: (1) determine the interaction between cognitive load and balance in children and young adults with bilateral cochleovestibular dysfunction who use bilateral cochlear implants (CIs) and (2) determine the effect of an auditory balance prosthesis (the BalanCI) on this interaction. Many (20 to 70%) children with sensorineural hearing loss experience some degree of vestibular loss, leading to poorer balance. Poor balance could have effects on cognitive resource allocation which might be alleviated by the BalanCI as it translates head-referenced cues into electrical pulses delivered through the CI. It is hypothesized that children and young adults with cochleovestibular dysfunction will demonstrate greater dual-task costs than typically-developing children during dual balance-cognition tasks, and that BalanCI use will improve performance on these tasks. DESIGN: Study participants were 15 typically-developing children (control group: mean age ± SD = 13.6 ± 2.75 years, 6 females) and 10 children and young adults who use bilateral CIs and have vestibular dysfunction (CI-V group: mean age ± SD=20.6 ± 5.36 years, 7 females). Participants completed two working memory tasks (backward auditory verbal digit span task and backward visuospatial dot matrix task) during three balance conditions: seated, standing in tandem stance with the BalanCI off, and standing in tandem stance with the BalanCI on. Working memory performance was quantified as total number of correct trials achieved. Postural stability was quantified as translational and rotational path length of motion capture markers worn on the head, upper body, pelvis, and feet, normalized by trial time. RESULTS: Relative to the control group, children and young adults in the CI-V group exhibited poorer overall working memory across all balance conditions ( p = 0.03), poorer translational postural stability (larger translational path length) during both verbal and visuospatial working memory tasks ( p < 0.001), and poorer rotational stability (larger rotational path length) during the verbal working memory task ( p = 0.026). The CI-V group also exhibited poorer translational ( p = 0.004) and rotational ( p < 0.001) postural stability during the backward verbal digit span task than backward visuospatial dot matrix task; BalanCI use reduced this stability difference between verbal and visuospatial working memory tasks for translational stability overall ( p > 0.9), as well as for rotational stability during the maximum working memory span (highest load) participants achieved in each task ( p = 0.91). CONCLUSIONS: Balance and working memory were impaired in the CI-V group compared with the control group. The BalanCI offered subtle improvements in stability in the CI-V group during a backward verbal working memory task, without producing a negative effect on working memory outcomes. This study supports the feasibility of the BalanCI as a balance prosthesis for individuals with cochleovestibular impairments.

Importance of early objective auditory testing in the presentation of sudden sensorineural hearing loss in children.

BACKGROUND: Functional hearing loss can be due to an auditory manifestation of functional neurological disorder, previously known as conversion disorder. METHODS: This is a case series of 3 pediatric patients with a diagnosis of idiopathic SSNHL who ultimately were found to have functional neurological disorder. RESULTS: Average age was 12.7 years at presentation (range 10-14 years). All three patients underwent invasive interventions prior to their initial clinic visit. All patients demonstrated profound SNHL on behavioural audiogram, but normal otoacoustic emissions (OAE) and auditory brainstem response testing. With counselling, both patients demonstrated significant hearing improvement. CONCLUSIONS: Early use of OAE's in the workup of SSNHL can avoid unnecessary and potentially harmful therapies and expedite access to counselling services which may help lead to symptom resolution.

Longitudinal Effects of Simultaneous and Sequential Bilateral Cochlear Implantation on Cortical Auditory-Evoked Potentials Recorded at Cz in a Large Cohort of Children.

OBJECTIVES: Auditory development after bilateral cochlear implantation in children has been measured using source localization of multi-channel late latency responses. It is not clear, however, whether this development can be tracked using a more clinically feasible method of recording from one active recording electrode placed at mid-line center of the head (Cz). DESIGN: In this prospective cohort study, cortical auditory-evoked potential responses (CAEPs) were recorded from Cz referenced to each earlobe (Cz-CAEP) from 222 children with bilateral cochlear implant (CI); 128 (mean ± SD age: 2.78 ± 3.30 years) received both CIs in the same surgery (simultaneous group) and 94 (aged 7.72 ± 4.45 years) received a second CI after 4.21 ± 2.98 years of unilateral CI use. We sought to (1) identify cortical development over the first couple of years of bilateral CI use; (2) measure known asymmetries in auditory development between the CIs; and (3) detect the effects of bilateral rather than unilateral CI use. 4556 Cz-CAEPs were recorded across the cohort over 33.50 ± 7.67 months duration of bilateral CI use. Given concerns related to peak picking, amplitude areas were measured across two response time windows (50 to 199 ms and 200 to 400 ms). RESULTS: Results indicated that small response amplitudes occur at initial CI use and amplitudes increase in the negative or positive direction rapidly over the first months of CI use in both time windows. Asymmetries between Cz-CAEPs evoked by each CI were found in the sequential group and reduced with bilateral CI use, particularly in the first time window; these differences increased with longer inter-implant delay. Bilaterally evoked Cz-CAEPs were larger in amplitude than unilateral responses from either CI in the simultaneous group. In the sequential group, bilateral responses were similar to responses from the first implanted side but increased in relative amplitude with bilateral CI use. The Cz-CAEP measures were not able to predict asymmetries or bilateral benefits in speech perception measures. CONCLUSIONS: The Cz-CAEP was able to indicate cortical detection of CI input and showed gross morphological changes with bilateral CI use. Findings indicate Cz-CAEPs can be used to identify gross changes in auditory development in children with bilateral CIs, but they are less sensitive to tracking the remaining abnormalities that are measured by multi-channel CAEPs and speech perception testing.

Further delineation of auriculocondylar syndrome based on 14 novel cases and reassessment of 25 published cases.

Auriculocondylar syndrome (ACS) is a rare craniofacial disorder characterized by mandibular hypoplasia and an auricular defect at the junction between the lobe and helix, known as a "Question Mark Ear" (QME). Several additional features, originating from the first and second branchial arches and other tissues, have also been reported. ACS is genetically heterogeneous with autosomal dominant and recessive modes of inheritance. The mutations identified to date are presumed to dysregulate the endothelin 1 signaling pathway. Here we describe 14 novel cases and reassess 25 published cases of ACS through a questionnaire for systematic data collection. All patients harbor mutation(s) in PLCB4, GNAI3, or EDN1. This series of patients contributes to the characterization of additional features occasionally associated with ACS such as respiratory, costal, neurodevelopmental, and genital anomalies, and provides management and monitoring recommendations.

Cortical imbalance following delayed restoration of bilateral hearing in deaf adolescents.

Unilateral auditory deprivation in early childhood can lead to cortical strengthening of inputs from the stimulated side, yet the impact of this on bilateral processing when inputs are later restored beyond an early sensitive period is unknown. To address this, we conducted a longitudinal study with 13 bilaterally profoundly deaf adolescents who received unilateral access to sound via a cochlear implant (CI) in their right ear in early childhood before receiving bilateral access to sound a decade later via a second CI in their left ear. Auditory-evoked cortical responses to unilateral and bilateral stimulation were measured repeatedly using electroencephalogram from 1 week to 14 months after activation of their second CI. Early cortical responses from the newly implanted ear and bilateral stimulation were atypically lateralized to the left ipsilateral auditory cortex. Duration of unilateral deafness predicted an unexpectedly stronger representation of inputs from the newly implanted, compared to the first implanted ear, in left auditory cortex. Significant initial reductions in responses were observed, yet a left-hemisphere bias and unequal weighting of inputs favoring the long-term deaf ear did not converge to a balanced state observed in the binaurally developed system. Bilateral response enhancement was significantly reduced in left auditory cortex suggesting deficits in ipsilateral response inhibition of new, dominant, inputs during bilateral processing. These findings paradoxically demonstrate the adaptive capacity of the adolescent auditory system beyond an early sensitive period for bilateral input, as well as restrictions on its potential to fully reverse cortical imbalances driven by long-term unilateral deafness.

Combination mTOR and SHP2 inhibitor treatment of lymphatic malformation endothelial cells.

Mammalian target of rapamycin (mTOR) inhibitors are clinically effective at treating some complex lymphatic malformations (LM). The mTOR inhibitor rapamycin blocks the phosphoinositide 3-kinase (PI3K) pathway, which is commonly mutated in this condition. Although rapamycin is effective at controlling symptoms of LM, treatment courses are long, not all LMs respond to treatment, and many patients relapse after treatment has stopped. Concurrent rat sarcoma virus (RAS) pathway abnormalities have been identified in LM, which may limit the effectiveness of rapamycin. Protein tyrosine phosphatase-2 (SHP2) controls the RAS pathway upstream, and SHP2 inhibitors are being investigated for treatment of various tumors. The objective of this study was to determine the impact of SHP2 inhibition in combination with rapamycin on LM growth in vitro. Using primary patient cells isolated from a surgically resected LM, we found that combination treatment with rapamycin and the SHP2 inhibitor SHP099 caused a synergistic reduction in cell growth, migration and lymphangiogenesis. These results suggest that combination treatment targeting the PI3K and RAS signaling pathways may result in effective treatment of LMs of the head and neck.

Button battery taping prevents oesophageal injury.

AIM: Most button battery (BB) ingestions in children are unwitnessed leading to prolonged exposures and severe complications. One third of ingestions occur from free BB, that are stored or awaiting disposal. Recommendations have been made to cover the terminals of discarded BB with adhesive tape; however, it is unclear if this practice prevents injury. Our aim was to determine if tape could prevent oesophageal injury in a cadaveric porcine model. METHODS: Electrical, masking, packing and duct tape were compared. One BB was left untaped. Taped BBs were placed in a cadaveric porcine oesophagus controlled for temperature and humidification. Specimens were assessed at 0, 0.5, and hourly for 6 h by visual inspection, temperature and pH. BB voltage was measured before and after testing. All tests were repeated in triplicate. RESULTS: Oesophageal specimens demonstrated burn prevention in the packing and duct tape trials. Burns were seen in 2/3 trials with electrical tape and 3/3 trials with masking tape. pH remained neutral throughout the study for all packing and duct tape specimens. pH remained neutral initially for masking tape but increased rapidly to 12 by 2 h. There was no change in battery voltage for the packing tape and duct tape trials. There was a 16.3% reduction in voltage for masking tape which was similar to controls. CONCLUSIONS: Taping BB with packing tape and duct tape prevented oesophageal burns. This may provide a novel method of burn prevention for loose BB intended for disposal.

Interhemispheric auditory connectivity requires normal access to sound in both ears during development.

Despite early bilateral cochlear implantation, children with congenital deafness do not develop accurate spatial hearing; we thus asked whether auditory brain networks are disrupted in these children. EEG responses were evoked unilaterally and bilaterally in 13 children with normal hearing and 16 children receiving bilateral cochlear implants simultaneously. Active cortical areas were estimated by the Time Restricted Artifact and Coherent source Suppression (TRACS) beamformer and connected cortical areas were identified by measuring coherence between source responses. A whole-brain analysis of theta band coherence revealed the strongest connections between the temporal areas in all conditions at early latencies. Stronger imaginary coherence in activity between the two auditory cortices to bilateral than unilateral input was found in children with normal hearing reflecting facilitation in the auditory network during bilateral hearing. The opposite effect, depressed coherence, was found during bilateral stimulation in children using cochlear implants. Children with cochlear implants also showed a unique auditory network in response to bilateral stimulation which was marked by increased connectivity between occipital and frontal areas. These findings suggest that cortical networks for sound processing are normally facilitated by bilateral input but are disrupted in children who hear through two independent cochlear implants. Efforts to improve hearing in children with congenital deafness must thus include corrections to potential mismatches in bilateral input to support brain development.

CHARGE and Kabuki Syndromes: Gene-Specific DNA Methylation Signatures Identify Epigenetic Mechanisms Linking These Clinically Overlapping Conditions.

Epigenetic dysregulation has emerged as a recurring mechanism in the etiology of neurodevelopmental disorders. Two such disorders, CHARGE and Kabuki syndromes, result from loss of function mutations in chromodomain helicase DNA-binding protein 7 (CHD7LOF) and lysine (K) methyltransferase 2D (KMT2DLOF), respectively. Although these two syndromes are clinically distinct, there is significant phenotypic overlap. We therefore expected that epigenetically driven developmental pathways regulated by CHD7 and KMT2D would overlap and that DNA methylation (DNAm) alterations downstream of the mutations in these genes would identify common target genes, elucidating a mechanistic link between these two conditions, as well as specific target genes for each disorder. Genome-wide DNAm profiles in individuals with CHARGE and Kabuki syndromes with CHD7LOF or KMT2DLOF identified distinct sets of DNAm differences in each of the disorders, which were used to generate two unique, highly specific and sensitive DNAm signatures. These DNAm signatures were able to differentiate pathogenic mutations in these two genes from controls and from each other. Analysis of the DNAm targets in each gene-specific signature identified both common gene targets, including homeobox A5 (HOXA5), which could account for some of the clinical overlap in CHARGE and Kabuki syndromes, as well as distinct gene targets. Our findings demonstrate how characterization of the epigenome can contribute to our understanding of disease pathophysiology for epigenetic disorders, paving the way for explorations of novel therapeutics.

Electrical Vestibular Stimulation in Humans: A Narrative Review.

BACKGROUND: In patients with bilateral vestibulopathy, the regular treatment options, such as medication, surgery, and/or vestibular rehabilitation, do not always suffice. Therefore, the focus in this field of vestibular research shifted to electrical vestibular stimulation (EVS) and the development of a system capable of artificially restoring the vestibular function. Key Message: Currently, three approaches are being investigated: vestibular co-stimulation with a cochlear implant (CI), EVS with a vestibular implant (VI), and galvanic vestibular stimulation (GVS). All three applications show promising results but due to conceptual differences and the experimental state, a consensus on which application is the most ideal for which type of patient is still missing. SUMMARY: Vestibular co-stimulation with a CI is based on "spread of excitation," which is a phenomenon that occurs when the currents from the CI spread to the surrounding structures and stimulate them. It has been shown that CI activation can indeed result in stimulation of the vestibular structures. Therefore, the question was raised whether vestibular co-stimulation can be functionally used in patients with bilateral vestibulopathy. A more direct vestibular stimulation method can be accomplished by implantation and activation of a VI. The concept of the VI is based on the technology and principles of the CI. Different VI prototypes are currently being evaluated regarding feasibility and functionality. So far, all of them were capable of activating different types of vestibular reflexes. A third stimulation method is GVS, which requires the use of surface electrodes instead of an implanted electrode array. However, as the currents are sent through the skull from one mastoid to the other, GVS is rather unspecific. It should be mentioned though, that the reported spread of excitation in both CI and VI use also seems to induce a more unspecific stimulation. Although all three applications of EVS were shown to be effective, it has yet to be defined which option is more desirable based on applicability and efficiency. It is possible and even likely that there is a place for all three approaches, given the diversity of the patient population who serves to gain from such technologies.

BalanCI: Head-Referenced Cochlear Implant Stimulation Improves Balance in Children with Bilateral Cochleovestibular Loss.

INTRODUCTION: To determine the impact of a head-referenced cochlear implant (CI) stimulation system, BalanCI, on balance and postural control in children with bilateral cochleovestibular loss (BCVL) who use bilateral CI. METHODS: Prospective, blinded case-control study. Balance and postural control testing occurred in two settings: (1) quiet clinical setting and (2) immersive realistic virtual environment (Challenging Environment Assessment Laboratory [CEAL], Toronto Rehabilitation Institute). Postural control was assessed in 16 and balance in 10 children with BCVL who use bilateral CI, along with 10 typically developing children. Children with neuromotor, cognitive, or visual deficits that would prevent them from performing the tests were excluded. Children wore the BalanCI, which is a head-mounted device that couples with their CIs through the audio port and provides head-referenced spatial information delivered via the intracochlear electrode array. Postural control was measured by center of pressure (COP) and time to fall using the WiiTM (Nintendo, WA, USA) Balance Board for feet and the BalanCI for head, during the administration of the Modified Clinical Test of Sensory Interaction in Balance (CTSIB-M). The COP of the head and feet were assessed for change by deviation, measured as root mean square around the COP (COP-RMS), rate of deviation (COP-RMS/duration), and rate of path length change from center (COP-velocity). Balance was assessed by the Bruininks-Oseretsky Test of Motor Proficiency 2, balance subtest (BOT-2), specifically, BOT-2 score as well as time to fall/fault. RESULTS: In the virtual environment, children demonstrated more stable balance when using BalanCI as measured by an improvement in BOT-2 scores. In a quiet clinical setting, the use of BalanCI led to improved postural control as demonstrated by significant reductions in COP-RMS and COP-velocity. With the use of BalanCI, the number of falls/faults was significantly reduced and time to fall increased. CONCLUSIONS: BalanCI is a simple and effective means of improving postural control and balance in children with BCVL who use bilateral CI. BalanCI could potentially improve the safety of these children, reduce the effort they expend maintaining balance and allow them to take part in more complex balance tasks where sensory information may be limited and/or noisy.

Cochlear Implant Use Remains Consistent Over Time in Children With Single-Sided Deafness.

OBJECTIVES: To measure the acceptance of a cochlear implant by children with single-sided deafness (SSD) using datalogging technology in the cochlear implant processor. DESIGN: Datalogs from follow-up clinical audiology appointments for 23 children with SSD were extracted from their cochlear implant processors ranging from 1 to 8 visits (M = 3.74, SD = 1.79). The number of hours the cochlear implant was in use per day, the number of times the coil disconnected from the internal device, and the percentage of daily cochlear implant use in different auditory environments were collected from the datalogs. Linear mixed-effects regressions were used to analyze the relationship between age, hearing experience, cochlear implant use, and coil-offs per day. Nonlinear regressions were conducted to evaluate cochlear implant use in different environments. RESULTS: Children with SSD wore their cochlear implants for 6.22 (SD = 2.81; range = 0.0004 to 14.74) hours per day on average. No significant change in cochlear implant use was seen as the children grew older or gained more hearing experience. As hearing experience increased, the number of coil-offs per day was reduced. Preschoolers spent more time in "music" and "speech" and less time in "noise" and "quiet" than older and younger children while older children spent more time in "speech-in-noise." CONCLUSIONS: Children with SSD consistently wear their cochlear implants. However, the auditory environments to which they are exposed vary over time. Regular cochlear implant use by this population suggests that it does not detract from a normal-hearing ear and that children with SSD appreciate access to bilateral input.

"Aural Patching" After Bilateral Cochlear Implantation Is Challenging for Children With Prior Long-Term Unilateral Implant Experience.

OBJECTIVES: To assess the use of "aural patching" as a strategy to potentially reduce the known persistence of aural preference in children receiving bilateral cochlear implants (CIs) with long inter-implant delays by removing the first device to increase stimulation to the second implanted side. DESIGN: Children/adolescents who received a second CI at 12.8 ± 3.5 years of age after 9.4 ± 2.9 years of unilateral CI use were asked to remove their first CI for regular periods daily (aural patching). Their compliance was monitored, and asymmetries in speech perception were measured at the end of the study period. RESULTS: Partial adherence to aural patching over the first few months of bilateral hearing use markedly declined with time. As expected, the group demonstrated asymmetries in speech perception that were not significantly affected by the limited aural patching. CONCLUSIONS: The aural patching protocol was a challenge to maintain for most children and families studied, reflecting both the expected aural preference for the first implanted ear and their challenges to reverse it.

Binaural hearing is impaired in children with hearing loss who use bilateral hearing aids.

This paper asked whether children fitted with bilateral hearing aids (BHA) develop normal perception of binaural cues which are the basis of spatial hearing. Data from children with BHA (n = 26, age = 12.6 ± 2.84 years) were compared to data from a control group (n = 12, age = 12.36 ± 2.83 years). Stimuli were 250 Hz click-trains of 36 ms and a 40 ms consonant-vowel /da/ at 1 Hz presented through ER3A insert-earphones unilaterally or bilaterally. Bilateral stimuli were presented at different interaural level difference (ILD) and interaural timing difference (ITD) conditions. Participants indicated whether the sound came from the left or right side (lateralization) or whether one sound or two could be heard (binaural fusion). BHA children lateralized ILDs similarly to the control group but had impaired lateralization of ITDs. Longer response times relative to controls suggest that lateralization of ITDs was challenging for children with BHA. Most, but not all, of the BHA group were able to fuse click and speech sounds similarly to controls. Those unable to fuse showed particularly poor ITD lateralization. Results suggest that ITD perception is abnormal in children using BHAs, suggesting persistent effects of hearing loss that are not remediated by present clinical rehabilitation protocols.

Cortical Representation of Interaural Time Difference Is Impaired by Deafness in Development: Evidence from Children with Early Long-term Access to Sound through Bilateral Cochlear Implants Provided Simultaneously.

Accurate use of interaural time differences (ITDs) for spatial hearing may require access to bilateral auditory input during sensitive periods in human development. Providing bilateral cochlear implants (CIs) simultaneously promotes symmetrical development of bilateral auditory pathways but does not support normal ITD sensitivity. Thus, although binaural interactions are established by bilateral CIs in the auditory brainstem, potential deficits in cortical processing of ITDs remain. Cortical ITD processing in children with simultaneous bilateral CIs and normal hearing with similar time-in-sound was explored in the present study. Cortical activity evoked by bilateral stimuli with varying ITDs (0, ±0.4, ±1 ms) was recorded using multichannel electroencephalography. Source analyses indicated dominant activity in the right auditory cortex in both groups but limited ITD processing in children with bilateral CIs. In normal-hearing children, adult-like processing patterns were found underlying the immature P1 (∼100 ms) response peak with reduced activity in the auditory cortex ipsilateral to the leading ITD. Further, the left cortex showed a stronger preference than the right cortex for stimuli leading from the contralateral hemifield. By contrast, children with CIs demonstrated reduced ITD-related changes in both auditory cortices. Decreased parieto-occipital activity, possibly involved in spatial processing, was also revealed in children with CIs. Thus, simultaneous bilateral implantation in young children maintains right cortical dominance during binaural processing but does not fully overcome effects of deafness using present CI devices. Protection of bilateral pathways through simultaneous implantation might be capitalized for ITD processing with signal processing advances, which more consistently represent binaural timing cues.SIGNIFICANCE STATEMENT Multichannel electroencephalography demonstrated impairment of binaural processing in children who are deaf despite early access to bilateral auditory input by first finding that foundations for binaural hearing are normally established during early stages of cortical development. Although 4- to 7-year-old children with normal hearing had immature cortical responses, adult patterns in cortical coding of binaural timing cues were measured. Second, children receiving two cochlear implants in the same surgery maintained normal-like input from both ears, but this did not support significant effects of binaural timing cues in either auditory cortex. Deficits in parieto-occiptal areas further suggested impairment in spatial processing. Results indicate that cochlear implants working independently in each ear do not fully overcome deafness-related binaural processing deficits, even after long-term experience.

Cortical hemispheric asymmetries are present at young ages and further develop into adolescence.

Specialization of the auditory cortices for pure tone listening may develop with age. In adults, the right hemisphere dominates when listening to pure tones and music; we thus hypothesized that (a) asymmetric function between auditory cortices increases with age and (b) this development is specific to tonal rather than broadband/non-tonal stimuli. Cortical responses to tone-bursts and broadband click-trains were recorded by multichannel electroencephalography in young children (5.1 ± 0.8 years old) and adolescents (15.2 ± 1.7 years old) with normal hearing. Peak dipole moments indicating activity strength in right and left auditory cortices were calculated using the Time Restricted, Artefact and Coherence source Suppression (TRACS) beamformer. Monaural click-trains and tone-bursts in young children evoked a dominant response in the contralateral right cortex by left ear stimulation and, similarly, a contralateral left cortex response to click-trains in the right ear. Responses to tone-bursts in the right ear were more bilateral. In adolescents, peak activity dominated in the right cortex in most conditions (tone-bursts from either ear and to clicks from the left ear). Bilateral activity was evoked by right ear click stimulation. Thus, right hemispheric specialization for monaural tonal stimuli begins in children as young as 5 years of age and becomes more prominent by adolescence. These changes were marked by consistent dipole moments in the right auditory cortex with age in contrast to decreases in dipole activity in all other stimulus conditions. Together, the findings reveal increasingly asymmetric function for the two auditory cortices, potentially to support greater cortical specialization with development into adolescence.

Warsaw breakage syndrome: Further clinical and genetic delineation.

Warsaw breakage syndrome (WBS) is a recently recognized DDX11-related rare cohesinopathy, characterized by severe prenatal and postnatal growth restriction, microcephaly, developmental delay, cochlear anomalies, and sensorineural hearing loss. Only seven cases have been reported in the English literature, and thus the information on the phenotype and genotype of this interesting condition is limited. We provide clinical and molecular information on five additional unrelated patients carrying novel bi-allelic variants in the DDX11 gene, identified via whole exome sequencing. One of the variants was found to be a novel Saudi founder variant. All identified variants were classified as pathogenic or likely pathogenic except for one that was initially classified as a variant of unknown significance (VOUS) (p.Arg378Pro). Functional characterization of this VOUS using heterologous expression of wild type and mutant DDX11 revealed a marked effect on protein stability, thus confirming pathogenicity of this variant. The phenotypic data of the seven WBS reported patients were compared to our patients for further phenotypic delineation. Although all the reported patients had cochlear hypoplasia, one patient also had posterior labyrinthine anomaly. We conclude that while the cardinal clinical features in WBS (microcephaly, growth retardation, and cochlear anomalies) are almost universally present, the breakage phenotype is highly variable and can be absent in some cases. This report further expands the knowledge of the phenotypic and molecular features of WBS.

Cortical Processing of Level Cues for Spatial Hearing is Impaired in Children with Prelingual Deafness Despite Early Bilateral Access to Sound.

Bilateral cochlear implantation aims to restore binaural hearing, important for spatial hearing, to children who are deaf. Improvements over unilateral implant use are attributed largely to the detection of interaural level differences (ILDs) but emerging evidence of impaired sound localization and binaural fusion suggest that these binaural cues are abnormally coded by the auditory system. We used multichannel electroencephalography (EEG) to assess cortical responses to ILDs in two groups: 13 children who received early bilateral cochlear implants (CIs) simultaneously, known to protect the developing auditory cortices from unilaterally driven reorganization, and 15 age matched peers with normal hearing. EEG source analyses indicated a dominance of right auditory cortex in both groups. Expected reductions in activity to ipsilaterally weighted ILDs were evident in the right hemisphere of children with normal hearing. By contrast, cortical activity in children with CIs showed: (1) limited ILD sensitivity in either cortical hemisphere, (2) limited correlation with reliable behavioral right-left lateralization of ILDs (in 10/12 CI users), and (3) deficits in parieto-occipital areas and the cerebellum. Thus, expected cortical ILD coding develops with normal hearing but is affected by developmental deafness despite early and simultaneous bilateral implantation. Findings suggest that impoverished fidelity of ILDs in independently functioning CIs may be impeding development of cortical ILD sensitivity in children who are deaf but do not altogether limit benefits of listening with bilateral CIs. Future efforts to provide consistent/accurate ILDs through auditory prostheses including CIs could improve binaural hearing for children with hearing loss.

Children With Single-Sided Deafness Use Their Cochlear Implant.

OBJECTIVES: To assess acceptance of a cochlear implant (CI) by children with single-sided deafness (SSD) as measured by duration of CI use across daily listening environments. DESIGN: Datalogs for 7 children aged 1.1 to 14.5 years (mean ± SD: 5.9 ± 5.9 years old), who had SSD and were implanted in their deaf ear, were anonymized and extracted from their CI processors. Data for all available follow-up clinical appointments were included, ranging from two to six visits. Measures calculated from each datalog included frequency and duration of time the coil disconnected from the internal device, average daily CI use, and both duration (hr/day) and percentage of CI use (% daily use) in different intensity ranges and environment types. Linear mixed effects regression analyses were used to evaluate the relationships between CI experience, daily CI use, frequency of coil-offs, and duration of coil-off time. Nonlinear regression analyses were used to evaluate CI use with age in different acoustic environments. RESULTS: Children with SSD used their CI on average 7.4 hr/day. Older children used their CI for longer periods of the day than younger children. Longitudinal data indicated consistent CI use from the date of CI activation. Frequency of coil-offs reduced with CI experience, but did not significantly contribute to hours of coil-off time. Children used their CI longest in environments that were moderately loud (50 to 70 dB A) and classified as containing speech-in-noise. Preschoolers tended to spend less time in quiet but more time in music than infants/toddlers and adolescents. CONCLUSIONS: Children with SSD consistently use their CI upon activation in a variety of environments commonly experienced by children. CI use in children with SSD resembles reported bilateral hearing aid use in children but is longer than reported hearing aid use in children with less severe unilateral hearing loss, suggesting that (1) the normal-hearing ear did not detract from consistent CI use; and (2) a greater asymmetry between ears presents a significant impairment that may facilitate device use to access bilateral sound.

Benefits of Music Training for Perception of Emotional Speech Prosody in Deaf Children With Cochlear Implants.

OBJECTIVES: Children who use cochlear implants (CIs) have characteristic pitch processing deficits leading to impairments in music perception and in understanding emotional intention in spoken language. Music training for normal-hearing children has previously been shown to benefit perception of emotional prosody. The purpose of the present study was to assess whether deaf children who use CIs obtain similar benefits from music training. We hypothesized that music training would lead to gains in auditory processing and that these gains would transfer to emotional speech prosody perception. DESIGN: Study participants were 18 child CI users (ages 6 to 15). Participants received either 6 months of music training (i.e., individualized piano lessons) or 6 months of visual art training (i.e., individualized painting lessons). Measures of music perception and emotional speech prosody perception were obtained pre-, mid-, and post-training. The Montreal Battery for Evaluation of Musical Abilities was used to measure five different aspects of music perception (scale, contour, interval, rhythm, and incidental memory). The emotional speech prosody task required participants to identify the emotional intention of a semantically neutral sentence under audio-only and audiovisual conditions. RESULTS: Music training led to improved performance on tasks requiring the discrimination of melodic contour and rhythm, as well as incidental memory for melodies. These improvements were predominantly found from mid- to post-training. Critically, music training also improved emotional speech prosody perception. Music training was most advantageous in audio-only conditions. Art training did not lead to the same improvements. CONCLUSIONS: Music training can lead to improvements in perception of music and emotional speech prosody, and thus may be an effective supplementary technique for supporting auditory rehabilitation following cochlear implantation.