Exposure to Spoken Communication During the COVID-19 Pandemic Among Children With Cochlear Implants.

Importance: School closures and other COVID-19-related restrictions could decrease children's exposure to speech during important stages of development. Objective: To assess whether significant decreases in exposure to spoken communication found during the initial phase of the COVID-19 pandemic among children using cochlear implants are confirmed for a larger cohort of children and were sustained over the first years of the COVID-19 pandemic. Design, Setting, and Participants: This cohort study used datalogs collected from children with cochlear implants during clinical visits to a tertiary pediatric hospital in Toronto, Ontario, Canada, from January 1, 2018, to November 11, 2021. Children with severe to profound hearing loss using cochlear implants were studied because their devices monitored and cataloged levels and types of sounds during hourly use per day (datalogs) and because their hearing and spoken language development was particularly vulnerable to reduced sound exposure. Statistical analyses were conducted between January 2022 and August 2023. Main Outcomes and Measures: Daily hours of sound were captured by the cochlear implant datalogging system and categorized into 6 auditory scene categories, including speech and speech-in-noise. Time exposed to speech was calculated as the sum of daily hours in speech and daily hours in speech-in-noise. Residual hearing in the ear without an implant of children with unilateral cochlear implants was measured by pure tone audiometry. Mixed-model regression analyses revealed main effects with post hoc adjustment of 95% CIs using the Satterthwaite method. Results: Datalogs (n = 2746) from 262 children (137 with simultaneous bilateral cochlear implants [74 boys (54.0%); mean (SD) age, 5.8 (3.5 years)], 38 with sequential bilateral cochlear implants [24 boys (63.2%); mean (SD) age, 9.1 (4.2) years], and 87 with unilateral cochlear implants [40 boys (46.0%); mean (SD) age, 7.9 (4.6) years]) who were preschool aged (n = 103) and school aged (n = 159) before the COVID-19 pandemic were included in analyses. There was a slight increase in use among preschool-aged bilateral cochlear implant users through the pandemic (early pandemic, 1.4 h/d [95% CI, 0.3-2.5 h/d]; late pandemic, 2.3 h/d [95% CI, 0.6-4.0 h/d]) and little change in use among school-aged bilateral cochlear implant users (early pandemic, -0.6 h/d [95% CI, -1.1 to -0.05 h/d]; late pandemic, -0.3 h/d [95% CI, -0.9 to 0.4 h/d]). However, use decreased during the late pandemic period among school-aged children with unilateral cochlear implants (-1.8 h/d [95% CI,-3.0 to -0.6 h/d]), particularly among children with good residual hearing in the ear without an implant. Prior to the pandemic, children were exposed to speech for approximately 50% of the time they used their cochlear implants (preschool-aged children: bilateral cochlear implants, 46.6% [95% CI, 46.5%-47.2%] and unilateral cochlear implants, 52.1% [95% CI, 50.7%-53.5%]; school-aged children: bilateral cochlear implants, 47.6% [95% CI, 46.8%-48.4%] and unilateral cochlear implants, 51.0% [95% CI, 49.4%-52.6%]). School-aged children in both groups experienced significantly decreased speech exposure in the early pandemic period (bilateral cochlear implants, -12.1% [-14.6% to -9.4%]; unilateral cochlear implants, -15.5% [-20.4% to -10.7%]) and late pandemic periods (bilateral cochlear implants, -5.3% [-8.0% to -2.6%]; unilateral cochlear implants, -11.2% [-15.3% to -7.1%]) compared with the prepandemic baseline. Conclusions and Relevance: This cohort study using datalogs from children using cochlear implants suggests that a sustained reduction in children's access to spoken communication was found during more than 2 years of COVID-19 pandemic-related lockdowns and school closures.

Effects of Age at Implantation on Outcomes of Cochlear Implantation in Children with Short Durations of Single-Sided Deafness.

OBJECTIVE: Children with single-sided deafness (SSD) show reduced language and academic development and report hearing challenges. We aim to improve outcomes in children with SSD by providing bilateral hearing through cochlear implantation of the deaf ear with minimal delay. STUDY DESIGN: Prospective cohort study of 57 children with SSD provided with cochlear implant (CI) between May 13, 2013, and June 25, 2021. SETTING: Tertiary children's hospital. PARTICIPANTS: Children with early onset (n = 40) or later onset of SSD (n = 17) received CIs at ages 2.47 ± 1.58 years (early onset group) and 11.67 ± 3.91 years (late onset group) (mean ± SD). Duration of unilateral deafness was limited (mean ± SD = 1.93 ± 1.56 yr). INTERVENTION: Cochlear implantation of the deaf ear. MAIN OUTCOMES/MEASURES: Evaluations of device use (data logging) and hearing (speech perception, effects of spatial release from masking on speech detection, localization of stationary and moving sound, self-reported hearing questionnaires). RESULTS: Results indicated that daily device use is variable (mean ± SD = 5.60 ± 2.97, range = 0.0-14.7 h/d) with particular challenges during extended COVID-19 lockdowns, including school closures (daily use reduced by mean 1.73 h). Speech perception with the CI alone improved (mean ± SD = 65.7 ± 26.4 RAU) but, in the late onset group, remained poorer than in the normal hearing ear. Measures of spatial release from masking also showed asymmetric hearing in the late onset group ( t13 = 5.14, p = 0.001). Localization of both stationary and moving sound was poor (mean ± SD error = 34.6° ± 16.7°) but slightly improved on the deaf side with CI use ( F1,36 = 3.95, p = 0.05). Decreased sound localization significantly correlated with poorer self-reported hearing. CONCLUSIONS AND RELEVANCE: Benefits of CI in children with limited durations of SSD may be more restricted for older children/adolescents. Spatial hearing challenges remain. Efforts to increase CI acceptance and consistent use are needed.

First Generation Osseointegrated Steady State Implant Benefits in Children With Hearing Loss.

OBJECTIVE: To assess outcomes of a new Osseointegrated Steady State Implant (OSSI) for bone conduction in adolescents. METHOD: In an initial trial, 14 adolescents (14.5 years of age, SD = 2.22) were provided with an OSSI; unilateral OSSI (n = 13), bilateral OSSI in sequential surgeries (n = 1). Outcomes measured were surgical duration, complications, hearing thresholds, speech perception and self-reported hearing benefits using the Speech and Spatial Quality of Hearing Questionnaire. RESULTS: The surgical times were mean 93.6 minutes (SD = 33.3). Surgery was slightly longer in three adolescents who required skin flap reduction (n = 1) or significant bone polishing (n = 2) (121.33 minutes, SD = 8.14). Adverse events occurred in two adolescents post-implant poor external device retention in one child requiring revision flap reduction and inflammation at the incision site due to magnet overuse in another. The "Digital Link Calibration" measure was a good proxy predictor of the strength of magnet required for external device adherence (p = 0.002). The OSSI increased audibility in the implanted ear by mean 31.48 dB HL (SE = 1.58). Aided thresholds were best at 1 kHz (mean 25.33 dB HL, SD = 22.60) and only slightly poorer at 3000 and 4000 Hz (estimate decrease = 8.33 dB HL, SE = 3.54), reflecting good auditory sensitivity even at high frequencies. Speech perception when using the new device alone was good (89.67%, SD = 7.84%) and self-reported hearing by participants and parents improved in all domains assessed by the Speech and Spatial Quality of Hearing Questionnaire (estimate = 1.90 points, SE = 0.25, p < 0.0001). CONCLUSION: The OSSI provides hearing benefits with surgical safety in a carefully selected cohort of adolescents.

Ultrasonic bone removal from the ossicular chain affects cochlear structure and function.

INTRODUCTION: Ultrasonic bone removal devices (UBD) are capable of cutting through bony tissue without injury to adjacent soft tissue. The feasibility and safety of using this technology for removal of bone from an intact ossicular chain (as might be required for otosclerosis or congenital fixation) was investigated in an animal model. METHODS: This was a prospective animal study conducted on seven anesthetised adult chinchillas. An UBD was used to remove bone from the malleus head in situ. Pre and post-operative distortion product otoacoustic emission (DPOAE) levels and auditory brainstem response (ABR) thresholds were recorded. Scanning electron microscopy (SEM) was used to assess cochlear haircell integrity. RESULTS: Precise removal of a small quantity of bone from the malleus head was achieved by a 30s application of UBD without disruption of the ossicular chain or tympanic membrane. DPOAEs became undetectable after the intervention with signal-to-noise ratios (SNR) < 5 dB SPL in all ears. Furthermore, ABR thresholds were elevated > 85 dB SPL in 13 ears. SEM showed significant disruption of structural integrity of the organ of Corti, specifically loss and damage of outer haircells. CONCLUSIONS: Although UBD can be used to reshape an ossicle without middle ear injury, prolonged contact with the ossicular chain can cause structural and functional injury to the cochlea. Extensive cochlea pathology was found, but we did not investigate for recovery from any temporary threshold shift. In the authors' opinion, further study should be undertaken before consideration is given to use of the device for release of ossicular fixation.

Exposure to Spoken Communication in Children With Cochlear Implants During the COVID-19 Lockdown.

Importance: The coronavirus disease 2019 (COVID-19) lockdowns in Ontario, Canada in the spring of 2020 created unprecedented changes in the lives of all children, including children with hearing loss. Objective: To quantify how these lockdowns changed the spoken communication environments of children with cochlear implants by comparing the sounds they were exposed to before the Ontario provincial state of emergency in March 2020 and during the resulting closures of schools and nonessential businesses. Design, Setting, and Participants: This experimental cohort study comprised children with hearing loss who used cochlear implants to hear. These children were chosen because (1) their devices monitor and catalog levels and types of sounds during hourly use per day (datalogs), and (2) this group is particularly vulnerable to reduced sound exposure. Children were recruited from the Cochlear Implant Program at a tertiary pediatric hospital in Ontario, Canada. Children whose cochlear implant datalogs were captured between February 1 and March 16, 2020, shortly before lockdown (pre-COVID-19), were identified. Repeated measures were collected in 45 children during initial easing of lockdown restrictions (stages 1-2 of the provincial recovery plan); resulting datalogs encompassed the lockdown period (peri-COVID-19). Main Outcomes and Measures: Hours of sound captured by the Cochlear Nucleus datalogging system (Cochlear Corporation) in 6 categories of input levels (<40, 40-49, 50-59, 60-69, 70-79, ≥80 A-weighted dB sound pressure levels [dBA]) and 6 auditory scene categories (quiet, speech, speech-in-noise, music, noise, and other). Mixed-model regression analyses revealed main effects with post hoc adjustment of confidence intervals using the Satterthwaite method. Results: A total of 45 children (mean [SD] age, 7.7 [5.0] years; 23 girls [51.1%]) participated in this cohort study. Results showed similar daily use of cochlear implants during the pre- and peri-COVID-19 periods (9.80 mean hours pre-COVID-19 and 9.34 mean hours peri-COVID-19). Despite consistent device use, these children experienced significant quieting of input sound levels peri-COVID-19 by 0.49 hour (95% CI, 0.21-0.80 hour) at 60 to 69 dBA and 1.70 hours (95% CI, 1.42-1.99 hours) at 70 to 79 dBA with clear reductions in speech exposure by 0.98 hour (95% CI, 0.49-1.47 hours). This outcome translated into a reduction of speech:quiet from 1.6:1.0 pre-COVID-19 to 0.9:1.0 during lockdowns. The greatest reductions in percentage of daily speech occurred in school-aged children (elementary, 12.32% [95% CI, 7.15%-17.49%]; middle school, 11.76% [95% CI, 5.00%-18.52%]; and high school, 9.60% [95% CI, 3.27%-15.93%]). Increased daily percentage of quiet (7.00% [95% CI, 4.27%-9.74%]) was most prevalent for children who had fewer numbers of people in their household (estimate [SE] = -1.12% [0.50%] per person; Cohen f = 0.31). Conclusions and Relevance: The findings of this cohort study indicate a clear association of COVID-19 lockdowns with a reduction in children's access to spoken communication.

Early Enzyme Replacement Therapy Improves Hearing and Immune Defects in Adenosine Deaminase Deficient-Mice.

Background: Inherited defects in adenosine deaminase (ADA) cause severe immune deficiency, which can be corrected by ADA enzyme replacement therapy (ERT). Additionally, ADA-deficient patients suffer from hearing impairment. We hypothesized that ADA-deficient (-/-) mice also exhibit hearing abnormalities and that ERT from an early age will improve the hearing and immune defects in these mice. Methods: Auditory brainstem evoked responses, organ weights, thymocytes numbers, and subpopulations, lymphocytes in peripheral blood as well as T lymphocytes in spleen were analyzed in ADA-/- and ADA-proficient littermate post-partum (pp). The cochlea was visualized by scanning electron microscopy (SEM). The effects of polyethylene glycol conjugated ADA (PEG-ADA) ERT or 40% oxygen initiated at 7 days pp on the hearing and immune abnormalities were assessed. Results: Markedly abnormal hearing thresholds responses were found in ADA-/- mice at low and medium tone frequencies. SEM demonstrated extensive damage to the cochlear hair cells of ADA-/- mice, which were splayed, short or missing, correlating with the hearing deficits. The hearing defects were not reversed when hypoxia in ADA-/- mice was corrected. Progressive immune abnormalities were detected in ADA-/- mice from 4 days pp, initially affecting the thymus followed by peripheral lymphocytes and T cells in the spleen. ERT initiated at 7 days pp significantly improved the hearing of ADA-/- mice as well as the number of thymocytes and T lymphocytes, although not all normalized. Conclusions: ADA deficiency is associated with hearing deficits and damage to cochlear hair cells. Early initiation of ERT improves the hearing and immune abnormalities.

Auditory neuropathy spectrum disorder (ANSD) and cochlear implantation.

We discuss issues related to cochlear implantation in children with auditory neuropathy spectrum disorder (ANSD). We describe the varied nature of this disease category including the numerous potential causes of auditory neuropathy. The most prevalent etiology for infants with ANSD is associated with prolonged neonatal intensive care unit (NICU) stay. We discuss the potential contribution of cochlear hypoxia to this etiology. The second part of this review describes in detail our own experience at the Hospital for Sick Children in Toronto, with cochlear implantation of children diagnosed with ANSD. We outline the detection, diagnosis, and referral routes for our patients. We provide an overview of our "standard operation procedures" regarding candidacy, and discuss some of the special considerations that need to be applied to children with ANSD. This includes decisions to implant children with better audiometric thresholds that are standard in non-ANSD patients, concerns about the possibility of spontaneous remission and the appropriate timing of implantation. Finally we review an extensive published literature in outcomes after cochlear implantation (CI) in ANSD. This is not a systematic review but rather an exercise to distill out some important reoccurring themes and the general consensus of opinion to date. Our conclusion is that the hearing loss category ANSD, together with its numerous co-morbidities, is far too heterogeneous to make definitive statements about prognosis with CI.

Time course of cochlear injury discharge (excitotoxicity) determined by ABR monitoring of contralateral cochlear events.

The dynamics of cochlear excitotoxicity can be monitored from effects on the contralateral ear. After unilateral mechanical ablation of the cochlea (in a mouse model) we observed immediate elevations in auditory brainstem evoked response (ABR) thresholds in the contralateral ear. Threshold elevations peaked at 2-3 h post ablation, and returned to baseline levels after 5-6 h. These contralateral effects are initiated by cochlear afferent injury discharges most likely activating the olivocochlear efferent system. Six hours after cochlear injury, ABR thresholds were fully returned to pre-lesion baseline levels and remained normal for up to 10 days of monitoring. We have confirmed that our cochlear ablation procedure increases short-term activity levels in the auditory brainstem and midbrain using c-fos labelling. The study provides insight into the dynamics of glutamate excitotoxicity, a pathological process directly related to acute tinnitus after acoustic trauma, and more generally implicated in many types of brain injury and neuro-degenerative disease.

Remodelling at the calyx of Held-MNTB synapse in mice developing with unilateral conductive hearing loss.

Structure and function of central synapses are profoundly influenced by experience during developmental sensitive periods. Sensory synapses, which are the indispensable interface for the developing brain to interact with its environment, are particularly plastic. In the auditory system, moderate forms of unilateral hearing loss during development are prevalent but the pre- and postsynaptic modifications that occur when hearing symmetry is perturbed are not well understood. We investigated this issue by performing experiments at the large calyx of Held synapse. Principal neurons of the medial nucleus of the trapezoid body (MNTB) are innervated by calyx of Held terminals that originate from the axons of globular bushy cells located in the contralateral ventral cochlear nucleus. We compared populations of synapses in the same animal that were either sound deprived (SD) or sound experienced (SE) after unilateral conductive hearing loss (CHL). Middle ear ossicles were removed 1 week prior to hearing onset (approx. postnatal day (P) 12) and morphological and electrophysiological approaches were applied to auditory brainstem slices taken from these mice at P17-19. Calyces in the SD and SE MNTB acquired their mature digitated morphology but these were structurally more complex than those in normal hearing mice. This was accompanied by bilateral decreases in initial EPSC amplitude and synaptic conductance despite the CHL being unilateral. During high-frequency stimulation, some SD synapses displayed short-term depression whereas others displayed short-term facilitation followed by slow depression similar to the heterogeneities observed in normal hearing mice. However SE synapses predominantly displayed short-term facilitation followed by slow depression which could be explained in part by the decrease in release probability. Furthermore, the excitability of principal cells in the SD MNTB had increased significantly. Despite these unilateral changes in short-term plasticity and excitability, heterogeneities in the spiking fidelity among the population of both SD and SE synapses showed similar continuums to those in normal hearing mice. Our study suggests that preservations in the heterogeneity in spiking fidelity via synaptic remodelling ensures symmetric functional stability which is probably important for retaining the capability to maximally code sound localization cues despite moderate asymmetries in hearing experience.

Angiogenesis in costal cartilage graft laryngotracheoplasty: a corrosion casting study in piglets.

OBJECTIVES/HYPOTHESIS: To investigate the timing and degree of angiogenesis following anterior costal cartilage graft laryngotracheoplasty in an animal model. STUDY DESIGN: Randomized controlled animal model. METHODS: Twelve pigs were included in this study. Three control pigs were perfused with intravascular methyl methacrylate, and overlying tissue was corroded with potassium hydroxide and hydrochloric acid, leaving only a cast of vessels. Nine pigs underwent anterior costal cartilage graft laryngotracheoplasty and were survived for various lengths of time (3 for 48 hours, 3 for 10 days, 3 for 3 weeks) prior to corrosion casting. Transition zones between trachea and cartilage graft as well as the graft itself were analyzed for signs of angiogenesis (budding, sprouting, intussusception) and hypoxic or degenerative vessel features (extravasation, corrugation, circular constriction) using scanning electron microscopy. RESULTS: Angiogenesis peaked above control levels 48 hours after laryngotracheoplasty (P < .0001) and decreased 10 days and 3 weeks following surgery (P < .001, P < .0001, respectively) while remaining elevated above control levels (P < .0001, P < .005, respectively). There was no difference in hypoxic or degenerative features across surgical and control groups. Sprouting angiogenesis dominated over intussusception preoperatively (P < .0001) and 3 weeks following surgery (P < .05). However, there was no difference in type of angiogenesis 48 hours and 10 days following surgery. CONCLUSION: Angiogenesis peaked by 48 hours following costal cartilage graft laryngotracheoplasty and persisted for at least 3 weeks (although decreased) after surgery in this animal model. Hypoxic or degenerative processes did not appear to play a role in tracheal revascularization during the first 3 postoperative weeks.

Attenuating Cardiac Pulsations within the Cochlea: Structure and Function of Tortuous Vessels Feeding Stria Vascularis.

The mammalian ear has an extraordinary capacity to detect very low-level acoustic signals from the environment. Sound pressures as low as a few µ Pa (-10 dB SPL) can activate cochlear hair cells. To achieve this sensitivity, biological noise has to be minimized including that generated by cardiovascular pulsation. Generally, cardiac pressure changes are transmitted to most peripheral capillary beds; however, such signals within the stria vascularis of the cochlea would be highly disruptive. Not least, it would result in a constant auditory sensation of heartbeat. We investigate special adaptations in cochlear vasculature that serve to attenuate cardiac pulse signals. We describe the structure of tortuous arterioles that feed stria vascularis as seen in corrosion casts of the cochlea. We provide a mathematical model to explain the role of this unique vascular anatomy in dampening pulsatile blood flow to the stria vascularis.

Corrosion casting of the subglottis following endotracheal tube intubation injury: a pilot study in Yorkshire piglets.

PURPOSE: Subglottic stenosis can result from endotracheal tube injury. The mechanism by which this occurs, however, is not well understood. The purpose of this study was to examine the role of angiogenesis, hypoxia and ischemia in subglottic mucosal injury following endotracheal intubation. METHODS: Six Yorkshire piglets were randomized to either a control group (N=3, ventilated through laryngeal mask airway for corrosion casting) or accelerated subglottic injury group through intubation and induced hypoxia as per a previously described model (N=3). The vasculature of all animals was injected with liquid methyl methacrylate. After polymerization, the surrounding tissue was corroded with potassium hydroxide. The subglottic region was evaluated using scanning electron microscopy looking for angiogenic and hypoxic or degenerative features and groups were compared using Mann-Whitney tests and Friedman's 2-way ANOVA. RESULTS: Animals in the accelerated subglottic injury group had less overall angiogenic features (P=.002) and more overall hypoxic/degenerative features (P=.000) compared with controls. Amongst angiogenic features, there was decreased budding (P=.000) and a trend toward decreased sprouting (P=.037) in the accelerated subglottic injury group with an increase in intussusception (P=.004), possibly representing early attempts at rapid revascularization. Amongst hypoxic/degenerative features, extravasation was the only feature that was significantly higher in the accelerated subglottic injury group (P=.000). CONCLUSIONS: Subglottic injury due to intubation and hypoxia may lead to decreased angiogenesis and increased blood vessel damage resulting in extravasation of fluid and a decreased propensity toward wound healing in this animal model.

Resting neural activity patterns in auditory brainstem and midbrain in conductive hearing loss.

CONCLUSIONS: Conductive hearing loss (CHL) lowers resting neural activity patterns in the auditory periphery. Such reductions of peripheral auditory activity may influence the developing central brain during early postnatal years when the system is still highly plastic. OBJECTIVES: A common cause of CHL in young children is otitis media; if chronic and/or episodic there may be a risk to speech and language development. In this clinical context we have investigated changes in neural activity patterns in the brainstem and midbrain in an animal model of CHL. METHODS: In a mouse model, a 50-60 dB CHL was produced by blocking the ear canals. We quantified resting neural activity patterns in the cochlear nucleus and inferior colliculus using c-fos immuno-labelling. This experimental group was compared with normal-hearing controls and with animals with bilateral cochlear ablation. RESULTS: Subjects with CHL had a statistically significant reduction in c-fos-labelled cells in the cochlear nucleus and central nucleus of the inferior colliculus compared with normal controls. This decreased c-fos expression suggests a change in resting neural activity generated at the inner hair cell synapse, leading to a reduction in activity levels in the ascending auditory pathways.

DIP/WISH deficiency enhances synaptic function and performance in the Barnes maze.

BACKGROUND: DIP (diaphanous interacting protein)/WISH (WASP interacting SH3 protein) is a protein involved in cytoskeletal signaling which regulates actin cytoskeleton dynamics and/or microtubules mainly through the activity of Rho-related proteins. Although it is well established that: 1) spine-head volumes change dynamically and reflect the strength of the synapse accompanying long-term functional plasticity of glutamatergic synaptic transmission and 2) actin organization is critically involved in spine formation, the involvement of DIP/WISH in these processes is unknown. RESULTS: We found that DIP/WISH-deficient hippocampal CA1 neurons exhibit enhanced long-term potentiation via modulation of both pre- and post-synaptic events. Consistent with these electrophysiological findings, DIP/WISH-deficient mice, particularly at a relatively young age, found the escape hole more rapidly in the Barnes maze test. CONCLUSIONS: We conclude that DIP/WISH deletion improves performance in the Barnes maze test in mice probably through increased hippocampal long-term potentiation.