Newborn auditory brainstem response and sudden infant death syndrome.

Sudden infant death syndrome (SIDS)-the sudden and unexplained death of a seemingly healthy infant, <1 year old-may be associated with abnormalities in the brain regions that underlie breathing and arousal during sleep. While post-mortem studies suggest abnormalities in SIDS infants' brainstems, there are no studies of these infants' brainstem function before death. One way to assess the function of the brainstem is with auditory brainstem response (ABR), a routine hearing-screening method that noninvasively measures the brainstem's response to sound. We hypothesize that anomalies in newborns' ABR measures may predict SIDS. Indeed, previous studies identified abnormalities in ABR characteristics in small samples of near-miss SIDS infants hospitalized for infant apnea syndrome. However, there is a need to examine the ABRs of infants who died of SIDS. Therefore, in the current study, we propose integrating two secondary datasets to examine newborns' ABRs (N = 156,972), including those who later died of SIDS (n = ~42; .27 out of every 1000 infants), using existing archived records of neonatal ABR results from a sample of newborns born in Florida. We hypothesize that infants who die from SIDS are more likely than non-SIDS infants to have abnormal ABRs as newborns. Understanding the association between SIDS and ABR may facilitate more accurate identification of an infant's risk for SIDS at birth, enabling increased monitoring, which may facilitate interventions and improve survivorship.

Novel standardized indexes of brainstem auditory evoked potentials for predicting hearing preservation in vestibular schwannomas.

Hearing preservation (HP) during vestibular schwannomas (VSs) surgery poses a significant challenge. Although brainstem auditory evoked potentials (BAEPs) on the affected side are commonly employed to monitor cochlear nerve function, their low signal-to-noise ratio (SNR) renders them susceptible to interferences, compromising their reliability. We retrospectively analyzed the data of patients who underwent tumor resection, while binaural brainstem auditory evoked potentials (BAEPs) were simultaneously recorded during surgery. To standardize BAEPs on the affected side, we incorporated the synchronous healthy side as a reference (interval between affected and healthy side ≤ 3 min). A total of 127 patients were enrolled. Comparison of the raw BAEPs data pre- and post-tumor resection revealed that neither V-wave amplitude (Am-V) nor latency (La-V) could serve as reliable predictors of HP simultaneously. However, following standardization, V-wave latency (STIAS-La-V) and amplitude (STIAS-Am-V) emerged as stable predictors of HP. Furthermore, the intraoperative difference in V-wave amplitude (D-Am-V) predicted postoperative HP in patients with preoperative HP and remained predictive after standardization. The utilization of intraoperative synchronous healthy side BAEPs as a reference to eliminate interferences proves to be an effective approach in enhancing the reliability of BAEPs for predicting HP in VSs patients.

Extending Subcortical EEG Responses to Continuous Speech to the Sound-Field.

The auditory brainstem response (ABR) is a valuable clinical tool for objective hearing assessment, which is conventionally detected by averaging neural responses to thousands of short stimuli. Progressing beyond these unnatural stimuli, brainstem responses to continuous speech presented via earphones have been recently detected using linear temporal response functions (TRFs). Here, we extend earlier studies by measuring subcortical responses to continuous speech presented in the sound-field, and assess the amount of data needed to estimate brainstem TRFs. Electroencephalography (EEG) was recorded from 24 normal hearing participants while they listened to clicks and stories presented via earphones and loudspeakers. Subcortical TRFs were computed after accounting for non-linear processing in the auditory periphery by either stimulus rectification or an auditory nerve model. Our results demonstrated that subcortical responses to continuous speech could be reliably measured in the sound-field. TRFs estimated using auditory nerve models outperformed simple rectification, and 16 minutes of data was sufficient for the TRFs of all participants to show clear wave V peaks for both earphones and sound-field stimuli. Subcortical TRFs to continuous speech were highly consistent in both earphone and sound-field conditions, and with click ABRs. However, sound-field TRFs required slightly more data (16 minutes) to achieve clear wave V peaks compared to earphone TRFs (12 minutes), possibly due to effects of room acoustics. By investigating subcortical responses to sound-field speech stimuli, this study lays the groundwork for bringing objective hearing assessment closer to real-life conditions, which may lead to improved hearing evaluations and smart hearing technologies.

Neurophysiological and brain structural insights into cyclin-dependent kinase-like 5 deficiency disorder: Visual and auditory evoked potentials and MRI analysis.

OBJECTIVE: CDKL5 deficiency disorder (CDD), an epileptic encephalopathy for which novel therapeutics are under development, lacks valid and reliable measures of therapeutic efficacy. We aimed to elucidate the neurophysiological and brain structural features of CDD patients and identify objective indicators reflecting the clinical severity. METHODS: Twelve CDD patients and 12 healthy controls (HCs) participated. The clinical severity of CDD was scored using the CDD severity assessment (CDD-SA). The participants underwent visual evoked potential (VEP), auditory brainstem response (ABR), structural MRI, and diffusion tensor imaging (DTI) analyses. Measurements from each modality were compared with normal values of age-matched cohorts (VEP and ABR) or statistically compared between CDD patients and HCs (MRI). RESULTS: VEP showed a significant correlation between P100 latency and CDD-SA in CDD patients. ABR showed abnormalities in six patients (50%), including prolonged V-wave latency (n = 2), prolonged inter-peak latency between waves I and V (n = 3), and mild hearing loss (n = 4). Structural MRI showed a significant reduction in cortical volume in the left pars triangularis and right cerebellum compared with HCs. DTI showed a widespread decrease in fractional anisotropy and an increase in mean and radial diffusivity compared with HCs. CONCLUSION: CDD patients had reduced cortical volume in the left pars triangularis, a brain region crucial for speech, and one-third of patients had mild hearing loss. These changes may be involved in language impairments in CDD patients. Additionally, P100 latency significantly correlated with the clinical severity. These features can be used to assess the clinical severity of CDD.

Electrically evoked auditory brainstem responses in deaf children with cochlear nerve canal stenosis.

BACKGROUND: Deaf children with cochlear nerve canal stenosis (CNCs) are always considered poor candidates for cochlear implantation. OBJECTIVES: To investigate the function of the peripheral auditory pathway in deaf children with CNCs, as revealed by the electrically evoked auditory brainstem response (EABR), and postoperative cochlear implants (CIs) outcomes. MATERIALS AND METHODS: Thirteen children with CNCs and 13 children with no inner ear malformations (IEMs) who received CIs were recruited. The EABR evoked by electrical stimulation from the CI electrode was recorded. Postoperative CI outcomes were assessed using Categories of Auditory Performance (CAP) and Speech Intelligibility Rate (SIR). RESULTS: Compared with children with no IEMs, children with CNCs showed lower EABR extraction rates, higher thresholds, a longer wave V (eV) latency and lower CAP and SIR scores. The auditory and speech performance was positively correlated with the diameter of the cochlear nerve canal and the number of channels showing wave III (eIII) and eV in children with CNCs. CONCLUSIONS AND SIGNIFICANCE: The physiological function of the peripheral auditory pathway in children with CNCs is poorer than that in children with no IEMs. Postoperative auditory and speech abilities may depend on the severity of cochlear nerve malformation and auditory conduction function.

Postnatal functional integrity of the brainstem auditory pathway in late preterm infants born of small-for-gestation age: how different from those born of appropriate-for-gestation.

It is unclear whether there is any postnatal abnormality in brainstem auditory function in late preterm small-for-gestational-age (SGA) infants. We investigated the functional integrity of the brainstem auditory pathway at 4 months after term in late preterm SGA infants and defined differences from appropriate-for-gestational age (AGA) infants. The maximum length sequence brainstem evoked response (MLS BAER) was recorded and analyzed in 24 SGA (birthweight < 3rd centile) infants and 28 AGA infants (birthweight > 10th centile). All infants were born at 33-36-week gestation without major perinatal and postnatal problems. We found that I-V interval in SGA infants was shorter than in AGA infants at higher click rates and significantly shorter at the highest rate of 910/s. Of the two smaller intervals, I-III interval was significantly shorter in SGA infants than in AGA infants at higher click rates of 455 and 910/s clicks, whereas III-V interval was similar in the two groups. The III-V/I-III interval ratio in SGA infants tended to be greater than in AGA infants at all rates and was significantly greater at 455 and 910/s clicks. The slope of I-III interval-rate functions in SGA infants was moderately smaller than in AGA infants.  Conclusions: The main and fundamental difference between late preterm SGA and AGA infants was a significant shortening in the MLS BAER I-III interval in SGA infants at higher click rates, suggesting moderately faster neural conduction in the caudal brainstem regions. Postnatal neural maturation in the caudal brainstem regions is moderately accelerated in late preterm SGA infants. What is Known: • At 40 weeks of postconceptional age, late preterm SGA infants manifested a mild delay in neural conduction in the auditory brainstem. What is New: • At 56 weeks of postconceptional age, late preterm SGA infants manifested moderately faster neural conduction in the caudal brainstem regions. • Postnatal neural maturation is moderately accelerated in the caudal brainstem regions of late preterm SGA infants.

Correlation of Grading and Number of Ear Subunits With Auditory Brainstem Response Findings in Children With Microtia.

PURPOSE: The association between microtia severity and hearing function has been thoroughly investigated. This study examined the relationship between microtia grade, number of ear subunits (i.e., helix, antihelix, scapha, triangularis fossa, concha, lobule, tragus, and antitragus) with auditory brainstem response (ABR) findings in children with microtia. STUDY DESIGN: A retrospective chart review was employed in this study. METHOD: We analyzed the ABR test results and photographs of 22 children with 30 microtia ears at Dr. Cipto Mangunkusumo National Hospital, Jakarta. The ABR test results were acquired using click (air conduction only) and 500-Hz tone burst stimuli (air- and bone-conduction). Ear photographs were overlaid with a template of a normal ear to determine the number of ear subunits present and the subsequent microtia grade. Number of ear subunits and ABR results were analyzed using the chi-square, Mann-Whitney U, and Spearman's correlation tests. RESULTS: ABR thresholds for click and 500-Hz tone bursts air-conduction were significantly poorer for ears with a subunit < 5 compared to ears with a subunit ≥ 5. No significant difference was observed in 500 Hz bone-conduction ABR thresholds between these groups. Correlation analysis showed a significant negative correlation between increased ear subunits and click ABR thresholds. No significant correlation was found between ear subunits and 500-Hz air- and bone-conduction ABR thresholds. CONCLUSIONS: A higher number of ear subunits are associated with a lower hearing threshold, as assessed using ABR with click stimuli. Therefore, the number of ear subunits and microtia grades can be used to examine the hearing level thresholds in infants and children with microtia. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25669440.

Infants with neonatal Chronic Lung Disease are associated with delayed auditory conduction in the rostral brainstem after term.

AIMS: Very Low Birthweight (VLBW) infants with neonatal Chronic Lung Disease (CLD) have been found to have functional impairment of the brainstem auditory pathway at term. This study investigated the functional status of the brainstem auditory pathway in VLBW infants with CLD after term for any abnormality. METHODS: Fifty-two VLBW infants were recruited at 50 weeks of Postconceptional Age: 25 with neonatal CLD and 27 without CLD. None had any other major complications to minimize confounding effects. Brainstem Auditory Evoked Responses were studied at 21‒91/s click rates. RESULTS: Compared with those without CLD, VLBW infants with CLD had relatively shorter latencies of BAER waves I and III, associated with a slightly lower BAER threshold. Wave V latency and I‒V interpeak interval did not differ significantly between the two groups of infants. The I‒III interval in infants with CLD was shorter than in those without CLD at 91/s clicks. However, the III‒V interval was significantly longer than in those without CLD at all click rates (all p < 0.05). There were no significant differences in the amplitudes of BAER wave components between the two groups of infants. CONCLUSIONS: The main BAER abnormality in VLBW infants with CLD was a prolonged III‒V interval. Auditory conduction is delayed or impaired at more central regions of the brainstem in CLD infants. After term central auditory function is adversely affected by neonatal CLD. Monitoring post-term change is required to provide valuable information for post-term care of CLD infants.

Correlation Analysis and Comparison of Adult CE-Chirp ABR Response Threshold and Pure Tone Hearing Threshold.

OBJECTIVES: To study the application of CE-Chirp in the evaluation of hearing impairment in forensic medicine by testing the auditory brainstem response (ABR) in adults using CE-Chirp to analyze the relationship between the V-wave response threshold of CE-Chirp ABR test and the pure tone hearing threshold. METHODS: Subjects (aged 20-77 with a total of 100 ears) who underwent CE-Chirp ABR test in Changzhou De'an Hospital from January 2018 to June 2019 were selected to obtain the V-wave response threshold, and pure tone air conduction hearing threshold tests were conducted at 0.5, 1.0, 2.0 and 4.0 kHz, respectively, to obtain pure tone listening threshold. The differences and statistical differences between the average pure tone hearing threshold and V-wave response threshold were compared in different hearing levels and different age groups. The correlation, differences and statistical differences between the two tests at each frequency were analyzed for all subjects. The linear regression equation for estimating pure tone hearing threshold for all subjects CE-Chirp ABR V-wave response threshold was established, and the feasibility of the equation was tested. RESULTS: There was no statistical significance in the CE-Chirp ABR response threshold and pure tone hearing threshold difference between different hearing level groups and different age groups (P>0.05). There was a good correlation between adult CE-Chirp ABR V-wave response threshold and pure tone hearing threshold with statistical significance (P<0.05), and linear regression analysis showed a significant linear correlation between the two (P<0.05). CONCLUSIONS: The use of CE-Chirp ABR V-wave response threshold can be used to evaluate subjects' pure tone hearing threshold under certain conditions, and can be used as an audiological test method for forensic hearing impairment assessment.

Intraoperative EABR Testing Predicts Strength of Cochlear Implant Stimulation Optimized After Long-Term Use in Pediatric Malformation Ears.

OBJECTIVE: This study focused on the intensities of cochlear implant (CI) stimulation in pediatric CI users with inner ear malformation or cochlear nerve deficiency (CND). In this population, CI programming is difficult because a large intensity of CI stimulation is required to achieve sufficient hearing, but the excess CI stimuli often induce facial nerve stimulation. We aimed to assess whether the results of intraoperative electrically evoked auditory brainstem responses (EABRs) testing predict maximum current levels of CI stimuli (cC levels) optimized by a behavioral-based method after long-term CI use. STUDY DESIGN: A retrospective case review. SETTING: A tertiary referral CI center. PATIENTS: A total of 116 ears with malformations (malformation group) and 63 control ears (control group) from patients younger than 18 years who received CI. The malformation group comprised 23 ears with a common cavity (CC), 26 with incomplete partition type 1 (IP-1), 26 with incomplete partition type 2 (IP-2), and 41 with CND. INTERVENTIONS: Diagnostic. MAIN OUTCOME MEASURES: Correlation between intraoperative EABR results and cC levels determined by the behavioral-based CI programming after long-term CI use. RESULTS: The CC, IP-1, and CND ears required significantly larger cC levels than the IP-2 ears and control groups. However, the cC levels increased to reach the plateau 1 year after surgery in all groups. Among the malformation group, 79 ears underwent intraoperative EABR testing. Greater than 80% of the CC, IP-1, and IP-2 ears and 54.8% of the CND ears exhibited evoked wave V (eV) and were included in the eV-positive category. Myogenic responses but no eV were observed in 18.2, 15.0, and 35.5% of the CC, IP-1, and CND ears, defined as the myogenic category. No eV or myogenic response was elicited in 9.7% of the CND ears. We focused on minimum current levels that elicited eV (eV levels) in the eV-positive category and maximum current levels that did not elicit any myogenic responses (myogenic levels) in the myogenic category. A significant relationship was detected between the eV levels and the cC levels. When analyzed in each malformation type, the eV levels significantly correlate with the cC levels in the CC and CND ears but not in the IP-1 and IP-2 ears, probably because of slight variation within the IP-1 group and the small number of the IP-2 group. The myogenic category did not show a significant relationship between the myogenic levels and cC levels, but the cC levels were similar to or smaller than the myogenic levels in most ears. CONCLUSIONS: This study confirmed that intraoperative EABR testing helps predict the optimal cC levels in malformation ears. EABR-based CI programming immediately after cochlear implantation, followed by behavioral-based CI programming, may allow us to achieve early postoperative optimization of CI maps even in young children with severe malformations.

Noise-induced synaptic loss and its post-exposure recovery in CBA/CaJ vs. C57BL/6J mice.

Acute noise-induced loss of synapses between inner hair cells (IHCs) and auditory nerve fibers (ANFs) has been documented in several strains of mice, but the extent of post-exposure recovery reportedly varies dramatically. If such inter-strain heterogeneity is real, it could be exploited to probe molecular pathways mediating neural remodeling in the adult cochlea. Here, we compared synaptopathy repair in CBA/CaJ vs. C57BL/6J, which are at opposite ends of the reported recovery spectrum. We evaluated C57BL/6J mice 0 h, 24 h, 2 wks or 8 wks after exposure for 2 h to octave-band noise (8-16 kHz) at either 90, 94 or 98 dB SPL, to compare with analogous post-exposure results in CBA/CaJ at 98 or 101 dB. We counted pre- and post-synaptic puncta in immunostained cochleas, using machine learning to classify paired (GluA2 and CtBP2) vs. orphan (CtBP2 only) puncta, and batch-processing to quantify immunostaining intensity. At 98 dB, both strains show ongoing loss of ribbons and synapses between 0 and 24 h, followed by partial recovery, however the extent and degree of these changes were greater in C57BL/6J. Much of the synaptic recovery is due to transient reduction in GluA2 intensity in synaptopathic regions. In contrast, CtBP2 intensity showed only transient increases (at 2 wks). Neurofilament staining revealed transient extension of ANF terminals in C57BL/6J, but not in CBA/CaJ, peaking at 24 h and reverting by 2 wks. Thus, although interstrain differences in synapse recovery are dominated by reversible changes in GluA2 receptor levels, the neurite extension seen in C57BL/6J suggests a qualitative difference in regenerative capacity.

From periphery to center, untold story of pure neuritic leprosy: an electrophysiological study.

BACKGROUND: Pure neuritic leprosy (PNL) is uncommon form of leprosy involving peripheral nerves. Some isolated case reports have shown imaging changes in the central nervous system (CNS) and also impairment in visual evoked potential (VEP), somatosensory evoked potential (SSEP) and brain stem auditory-evoked potentials (BAEPs) parameters in PNL, but there is lack of large study. This prospective observational study evaluates impairment in these central conduction studies among PNL patients. METHODS: We screened patients with leprosy presenting with features of neuropathy and/or thickened nerves. Patients with bacilli-positive nerve biopsies were included in the study and subjected to routine tests along with nerve conduction study (NCS), VEP, tibial SSEP and BAEPs. Parameters of these studies were analyzed based on data from previous studies. RESULTS: Of 76 patients screened for PNL 49 had positive findings in biopsy. Most of patients were male and mean age group was 46.35 ± 15.35 years. Mononeuritis multiplex was most common NCS pattern in 46.93% (23/49) patients. We found abnormal VEP in 13 out of 35 patients (37.14%). Similarly abnormal SSEP and BAEPs among 42.85% and 40% patients respectively. DISCUSSION: This study shows that in PNL significant number of patients have subclinical CNS involvement. Exact pathophysiology of CNS involvement is not known till now but study of VEP, SSEP and BAEPs parameter may help in early diagnosis of PNL.

Newborn Hearing Screening Results for Infants With Prenatal Opioid Exposure in Southern Appalachia.

PURPOSE: Infants prenatally exposed to opioids exhibit withdrawal symptomology that introduce physiological noise and can impact newborn hearing screening results. This study compared the referral rate and physiological noise interpreted by number of trials rejected due to artifact on initial newborn hearing screenings of infants with prenatal opioid exposure (POE) and infants with no opioid exposure (NOE). Furthermore, within the POE group, it examined the relationship of referral rates with severity of withdrawal symptomology, and with maternal and infant risk factors. METHOD: This study used a retrospective cohort design of electronic medical records from six delivery hospitals in South-Central Appalachia. Newborn hearing screenings were conducted using automated auditory brainstem response (ABR) for 334 infants with POE and 226 infants with NOE. Severity of withdrawal symptomology was measured using the Modified Finnegan Neonatal Abstinence Scoring Tool, which includes observation of behaviors that introduce physiological noise. RESULTS: There was no significant difference in newborn hearing screening referral rate between infants with POE and infants with NOE. Referral rate was not affected by maternal or infant risk factors. Infants with POE had statistically significant higher artifact (defined as rejected ABR sweeps) than infants with NOE. There was a strong positive correlation between Finnegan scores and artifact but not referral rates. Sensitivity and specificity analysis indicated artifact decreased substantially after Day 4 of life. CONCLUSIONS: Referral rates of infants with POE were similar to those of infants with NOE. Nevertheless, the withdrawal symptomology of infants with POE introduces physiological noise reflected as artifact on ABR, which can affect efficiency of newborn hearing screenings.

Intraoperative Brainstem Auditory Evoked Potentials and Postoperative Nausea and Vomiting After Microvascular Decompression.

BACKGROUND: We performed this study to investigate the effect of intraoperative brainstem auditory evoked potential (IBAEP) changes on the development of postoperative nausea and vomiting (PONV) after microvascular decompression (MVD) for neurovascular cross compression. METHODS: A total of 373 consecutive cases were treated with MVD. The use of rescue antiemetics after surgery was used as an objective indicator of PONV. IBAEP monitoring was routinely performed in all. RESULTS: The use of rescue antiemetics was significantly associated with female sex (OR = 3.427; 95% CI, 2.077-5.654; P < 0.001), PCA use (OR = 3.333; 95% CI, 1.861-5.104; P < 0.001), and operation time (OR = 1.017; 95% CI, 1.008-1.026; P < 0.001). A Wave V peak delay of more than 1.0 milliseconds showed a significant relation with the use of rescue antiemetics (OR = 1.787; 95% CI, 1.114-2.867; P = 0.016) and a strong significant relation with the use of rescue antiemetics more than 5 times (OR = 2.426; 95% CI, 1.372-4.290; P = 0.002). CONCLUSIONS: A wave V peak delay of more than 1.0 milliseconds might have value as a predictor of PONV after MVD. More detailed neurophysiological studies will identify the exact pathophysiology underlying PONV after MVD.

Sensorineural deafness in purebred white Devon Rex cats.

BACKGROUND: Data regarding congenital sensorineural deafness (CSD) in client-owned, white Devon Rex cats is limited because most of the information on this disease comes from experiments on mixed-breed cats. OBJECTIVES: Provide data on the occurrence of CSD in a population of client-owned purebred white Devon Rex cats. ANIMALS: Forty client-owned, purebred, white Devon Rex cats examined at 2 different facilities. Median age of the examined cats was 19 weeks. METHODS: Hearing status was defined by use of brainstem auditory evoked responses. RESULTS: The occurrence of sensorineural deafness in the studied population of Devon Rex cats was estimated at 10%. Unilateral and bilateral deafness occurred equally often, with 2 individuals having each (ie, 5.0%). No association between the occurrence of CSD and sex could be found, χ2 (1, n = 40) = 0.001 (P > .99). No association between blue irises and deafness was noted in the studied population, χ2 (1, n = 40) < 0.01 (P > .99). CONCLUSIONS: The occurrence of CSD in a population of client-owned, white Devon Rex cats was found to be lower compared with data obtained in previously conducted studies of deafness in purebred cats. In the studied population of Devon Rex cats, no association between blue irises and CSD was found.

Complete Restoration of Hearing Loss and Cochlear Synaptopathy via Minimally Invasive, Single-Dose, and Controllable Middle Ear Delivery of Brain-Derived Neurotrophic Factor-Poly(dl-lactic acid-co-glycolic acid)-Loaded Hydrogel.

Noise-induced hearing loss (NIHL) often accompanies cochlear synaptopathy, which can be potentially reversed to restore hearing. However, there has been little success in achieving complete recovery of sensorineural deafness using nearly noninvasive middle ear drug delivery before. Here, we present a study demonstrating the efficacy of a middle ear delivery system employing brain-derived neurotrophic factor (BDNF)-poly-(dl-lactic acid-co-glycolic acid) (PLGA)-loaded hydrogel in reversing synaptopathy and restoring hearing function in a mouse model with NIHL. The mouse model achieved using the single noise exposure (NE, 115 dBL, 4 h) exhibited an average 20 dBL elevation of hearing thresholds with intact cochlear hair cells but a loss of ribbon synapses as the primary cause of hearing impairment. We developed a BDNF-PLGA-loaded thermosensitive hydrogel, which was administered via a single controllable injection into the tympanic cavity of noise-exposed mice, allowing its presence in the middle ear for a duration of 2 weeks. This intervention resulted in complete restoration of NIHL at frequencies of click, 4, 8, 16, and 32 kHz. Moreover, the cochlear ribbon synapses exhibited significant recovery, whereas other cochlear components (hair cells and auditory nerves) remained unchanged. Additionally, the cochlea of NE treated mice revealed activation of tropomyosin receptor kinase B (TRKB) signaling upon exposure to BDNF. These findings demonstrate a controllable and minimally invasive therapeutic approach that utilizes a BDNF-PLGA-loaded hydrogel to restore NIHL by specifically repairing cochlear synaptopathy. This tailored middle ear delivery system holds great promise for achieving ideal clinical outcomes in the treatment of NIHL and cochlear synaptopathy.

Cochlear zinc signaling dysregulation is associated with noise-induced hearing loss, and zinc chelation enhances cochlear recovery.

Exposure to loud noise triggers sensory organ damage and degeneration that, in turn, leads to hearing loss. Despite the troublesome impact of noise-induced hearing loss (NIHL) in individuals and societies, treatment strategies that protect and restore hearing are few and insufficient. As such, identification and mechanistic understanding of the signaling pathways involved in NIHL are required. Biological zinc is mostly bound to proteins, where it plays major structural or catalytic roles; however, there is also a pool of unbound, mobile (labile) zinc. Labile zinc is mostly found in vesicles in secretory tissues, where it is released and plays a critical signaling role. In the brain, labile zinc fine-tunes neurotransmission and sensory processing. However, injury-induced dysregulation of labile zinc signaling contributes to neurodegeneration. Here, we tested whether zinc dysregulation occurs and contributes to NIHL in mice. We found that ZnT3, the vesicular zinc transporter responsible for loading zinc into vesicles, is expressed in cochlear hair cells and the spiral limbus, with labile zinc also present in the same areas. Soon after noise trauma, ZnT3 and zinc levels are significantly increased, and their subcellular localization is vastly altered. Disruption of zinc signaling, either via ZnT3 deletion or pharmacological zinc chelation, mitigated NIHL, as evidenced by enhanced auditory brainstem responses, distortion product otoacoustic emissions, and number of hair cell synapses. These data reveal that noise-induced zinc dysregulation is associated with cochlear dysfunction and recovery after NIHL, and point to zinc chelation as a potential treatment for mitigating NIHL.

Multisession anodal epidural direct current stimulation of the auditory cortex delays the progression of presbycusis in the Wistar rat.

Presbycusis or age-related hearing loss (ARHL) is one of the most prevalent chronic health problems facing aging populations. Along the auditory pathway, the stations involved in transmission and processing, function as a system of interconnected feedback loops. Regulating hierarchically auditory processing, auditory cortex (AC) neuromodulation can, accordingly, activate both peripheral and central plasticity after hearing loss. However, previous ARHL-prevention interventions have mainly focused on preserving the structural and functional integrity of the inner ear, overlooking the central auditory system. In this study, using an animal model of spontaneous ARHL, we aim at assessing the effects of multisession epidural direct current stimulation of the AC through stereotaxic implantation of a 1-mm silver ball anode in Wistar rats. Consisting of 7 sessions (0.1 mA/10 min), on alternate days, in awake animals, our stimulation protocol was applied at the onset of hearing loss (threshold shift detection at 16 months). Click- and pure-tone auditory brainstem responses (ABRs) were analyzed in two animal groups, namely electrically stimulated (ES) and non-stimulated (NES) sham controls, comparing recordings at 18 months of age. At 18 months, NES animals showed significantly increased threshold shifts, decreased wave amplitudes, and increased wave latencies after click and tonal ABRs, reflecting a significant, spontaneous ARHL evolution. Conversely, in ES animals, no significant differences were detected in any of these parameters when comparing 16 and 18 months ABRs, indicating a delay in ARHL progression. Electrode placement in the auditory cortex was accurate, and the stimulation did not cause significant damage, as shown by the limited presence of superficial reactive microglial cells after IBA1 immunostaining. In conclusion, multisession DC stimulation of the AC has a protective effect on auditory function, delaying the progression of presbycusis.

How 'hidden hearing loss' noise exposure affects neural coding in the inferior colliculus of rats.

Exposure to brief, intense sound can produce profound changes in the auditory system, from the internal structure of inner hair cells to reduced synaptic connections between the auditory nerves and the inner hair cells. Moreover, noisy environments can also lead to alterations in the auditory nerve or to processing changes in the auditory midbrain, all without affecting hearing thresholds. This so-called hidden hearing loss (HHL) has been shown in tinnitus patients and has been posited to account for hearing difficulties in noisy environments. However, much of the neuronal research thus far has investigated how HHL affects the response characteristics of individual fibres in the auditory nerve, as opposed to higher stations in the auditory pathway. Human models show that the auditory nerve encodes sound stochastically. Therefore, a sufficient reduction in nerve fibres could result in lowering the sampling of the acoustic scene below the minimum rate necessary to fully encode the scene, thus reducing the efficacy of sound encoding. Here, we examine how HHL affects the responses to frequency and intensity of neurons in the inferior colliculus of rats, and the duration and firing rate of those responses. Finally, we examined how shorter stimuli are encoded less effectively by the auditory midbrain than longer stimuli, and how this could lead to a clinical test for HHL.