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Key pointsr Severe forms of hearing loss during development are well known to profoundly alter synaptic structure and function through the auditory neuraxis; however, the pre-and postsynaptic modifications that occur during development following moderate forms of unilateral hearing loss remain unknown.r We performed anatomical and electrophysiological experiments at the calyx of Held synapse in slices taken from mature mice developing with a unilateral conductive hearing loss and compared populations of synapses in the same animal that were either sound deprived or sound experienced.r Compared to normal hearing mice, we found that calyx of Held synapses that were both sound deprived and sound experienced as a result of a unilateral conductive hearing loss were (1) structurally more complex, (2) had smaller synaptic currents and a readily releasable pool size, and (3) were more excitable.r Despite these changes in structure and function, spiking fidelity within the populations maintained a continuum as in normal hearing mice such that heterogeneities remained bilaterally symmetric.r Preservations in the heterogeneity in spiking fidelity via synaptic remodelling may ensure that a functional stability important for the ability to code sound localization cues is maintained despite asymmetries in hearing experience during development.Abstract 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 predomina...

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 PARTICIPANTSThis 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, Ն80 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 RELEVANCEThe findings of this cohort study indicate a clear association of COVID-19 lockdowns with a reduction in children's access to spoken communication.

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 ( t 13 = 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 ( F 1,36 = 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.

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.