Auditory Brainstem Response

The origins of cerebral asymmetry: A review of evidence of behavioural and brain lateralization in fishes, reptiles and amphibians. Neurosci. Biobehav. Rev., 22, 411-426. Britton, A. R. C. (2001). Review and classification of call types of juvenile crocodilians, and factors affecting distress calls. In Crocodilian Biology and Evolution (G. C. Grigg, F. Seebacher and C. E. Franklin, eds.). Surrey Beatty & Sons; Chipping Norton, NSW. Carothers, J. H., Groth, J. G. & Jaksic, F. M. (2001). Vocalization as a response to capture in the central Chilean lizard Liolaemus chiliensis (Tropiduridae).

Background: Congenital cytomegalovirus (CMV) disease, a common mother-to-child infection, can lead to neurological sequelae. Some clinical trials have shown that oral valganciclovir (VGCV) can improve hearing and neurodevelopmental impairment in infants with congenital CMV disease. However, VGCV has neither been approved in Japan nor other countries as a treatment for this disease by the government health insurance. Methods: This study is a non-randomized, prospective, open-label, multicenter, single-arm clinical trial and will include subjects meeting the following criteria: confirmation of positive CMV-DNA amplification in urine by an in vitro diagnostic test within 21 days of age; congenital CMV disease with one or more central nervous system disorders—microcephaly, hydrocephalus or ventricular enlargement, periventricular calcification, cortical hypoplasia or white matter injury, retinal choroiditis, and abnormal auditory brainstem response (ABR); and infants within 2 months of ...

Although earlier studies have shown that antiviral treatment regimens using valganciclovir (VGCV) improved hearing function in some infants with congenital cytomegalovirus (CMV) infection; its efficacy on the severity of hearing dysfunction is unclear. We conducted a prospective study among 26 infants with congenital CMV infections from 2009 to 2018. Oral VGCV (32 mg/kg/day) was administered for 6 weeks (November 2009 to June 2015; n = 20) or 6 months (July 2015 to March 2018, n = 6). Hearing function was evaluated by measuring the auditory brainstem response before VGCV treatment and at 6 months. Hearing dysfunction, defined as a V-wave threshold >40 dB, was categorized into: most severe, ≥91 dB; severe, 61–90 dB; and moderate, 41–60 dB. Hearing improvement was defined as a decrease of ≥20 dB from the pretreatment V-wave threshold. Of 52 ears in 26 infants with congenital CMV infection, 29 (56%) had hearing dysfunction, and of 29 ears, 16 (55%) improved after VGCV treatment. Alt...

Introduction: Binaural interaction component (BIC) served as an objective measure of binaural hearing function. It has been investigated through click or tone burst auditory brainstem response (ABR) but limited investigation was done using speech-evoked ABR (sABR).  This study aimed to investigate the presence of BIC in normal hearing young adults using /da/ stimulus in sABR. Methods: 23 participants aged between 18 and 25 years old participated in this study. sABR was conducted and BIC was mathematically derived by subtracting the binaural evoked responses from the sum of monoaural evoked responses, ie BIC = (Right + Left) – Binaural. BIC obtained was analysed descriptively. Results: BIC-V, BIC-A, BIC-D, BIC-E, BIC-F and BIC-O were detected in 80%, 40%, 70%, 70%, 55% and 50% of the subjects. The small amplitude of response peaks especially Peak A (mean: 0.061μV; SD: 0.053), Peak F (mean: -0.087μV; SD: 0.072) and Peak O (mean: -0.114μV; SD: 0.054) bewildered the visual detection of ...

Introduction Early screening for hearing loss is currently recognized as an international healthcare standard. In Cuba, such a program was initiated in the capital, Havana, in 1983 and scaled up to national coverage in 1991. Objective Review the development of Cuba's national hearing screening program over the last 25 years (organizational structure, efficiency, coverage and impact on health), and the science and technology developed to sustain it. The program was organized in two steps: Step 1-clinical selection of children at different stages of development with multiple high-risk registers; Step 2-referral to territorial, hospitalbased centers for auditory brainstem evoked response (ABR) testing, diagnostic evaluation, and intervention. Prior to national scaling-up, the efficiency of this multiple targeted screening (MTS) protocol was evaluated in Havana. Technology and equipment were then developed, and personnel were trained to set up the national screening network. In 1996, the multiple auditory steady-state evoked response (MSSR) technique for objective audiogram estimation was introduced using AUDIX equipment, designed and produced in Cuba for this program. A semi-automated version for neonatal screening has been developed more recently. Several studies have been conducted to evaluate the program's efficiency, coverage, yield, and impact on health. During the first stage of implementation in Havana, the MTS protocol correctly identified 72.5% of children with congenital and preverbal hearing loss. Subsequent studies of different aspects of the program have shown that: 1) the mean age of hearing loss detection/intervention in one municipality was reduced from 4 years to 10 months; 2) hearing-impaired children who were screened showed improved language and cognitive development compared to those who were not screened; 3) the MSSR technique predicted type and severity of hearing loss more accurately than physiological techniques used previously and was also shown to be an effective screening method (92% to 96% sensitivity, 100% specificity); and 4) program coverage (25-86%), though reasonably high in some regions, is not complete and needs improvement, particularly in the country's remote and rural areas. The MTS protocol can be considered a valid option for increasing the yield and effectiveness of a hearing screening program operating with limited resources. The MSSR technique provides valuable data for the diagnosis and treatment of children detected through a screening program and, with improvements, may also be useful as a screening method.

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 hypothesized that anomalies in newborns' ABR measures may predict SIDS. We integrated two secondary datasets and examined ABRs of newborns who later died of SIDS (n = 11) compared to a normative sample (n = 198,990), using existing archived records of neonatal ABR results from a sample of newborns born in Florida. As hypothesized, infants who died from SIDS were more likely than non-SIDS infants to have abnormal ABRs as newborns. Children who died of SIDS appeared to have shorter latencies to the trough that follows peak V in the left ear than children without SIDS. However, our expert-rated data failed to replicate this finding, suggesting it is unlikely to reflect a true effect. 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.

Speech delay with an unknown cause is a problem among children. This diagnosis is the last differential diagnosis after observing normal findings in routine hearing tests. The present study was undertaken to determine whether auditory brainstem responses to click stimuli are different between normally developing children and children suffering from delayed speech with unknown causes. In this cross-sectional study, we compared click auditory brainstem responses between 261 children who were clinically diagnosed with delayed speech with unknown causes based on normal routine auditory test findings and neurological examinations and had &gt;12 months of speech delay (case group) and 261 age- and sex-matched normally developing children (control group). Our results indicated that the case group exhibited significantly higher wave amplitude responses to click stimuli (waves I, III, and V) than did the control group (P=0.001). These amplitudes were significantly reduced after 1 year (P=0.0...

Automated Auditory Brain Response (AABR) devices are unique tools for neonate hearing screening programs. Contemporary utilization of AABR devices is based on two stimuli called chirp and click. The first study objective was to identify any possible differences in chirp and click stimulus results of the AABR devices in neonates. The second aim was to investigate any possible risk factor that could affect the results of each stimulus. Chirp and click stimuli were applied to each neonate using the AABR devices. Results were recorded automatically as pass or failed. Those with failed results were called after month for a retest. Hearing loss risk factors were obtained from the parents and caregivers. Twenty-one of the fifty-eight chirp stimuli gave negative results on the AABR in the second AABR test. Twenty-nine of the seventy-six click stimuli on the AABR gave a failed result on retest. The most common risk factors were consanguineous marriage of parents (n=184), history of being admitted to the neonatal intensive care unit (n=119), and jaundice (n=102). In addition, hearing loss was not detected in any neonate and was therefore not considered to significantly affect the results of the chirp or click stimulus on the AABR. We were unable to prove that the chirp stimulus could be replaced by the click stimuli in neonatal hearing screening using AABR device.

Fischer 344 (F344) rats represent a strain that is frequently used as a model for fast aging. In this study, we systematically compare the hearing function during aging in male and female F344 rats, by recording auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs). In addition to this, the functional parameters are correlated with the cochlear histology. The parameters of the hearing function were not different in the young (3-month-old) male and female F344 rats; the gender differences occurred only in adult and aged animals. In 8-24-month-old males, the ABR thresholds were higher and the ABR amplitudes were smaller than those measured in females of the same age. There were no gender differences in the neural adaptation tested by recording ABRs, elicited by a series of clicks with varying inter-click interval (ICI). Amplitudes of DPOAEs in both the males and females decreased with age, but in the males, the decrease of DPOAE amplitudes was faster. In males older than 20 months, the DPOAEs were practically absent, whereas in 20-24-month-old females, the DPOAEs were still measurable. There were no gender differences in the number of surviving outer hair cells (OHC) and the number of inner hair cell ribbon synapses in aged animals. The main difference was found in the stria vascularis (SV). Whereas the SV was well preserved in females up to the age of 24 months, in most of the age-matched males the SV was evidently deteriorated. The results demonstrate more pronounced age-related changes in the cochlear morphology, hearing thresholds, ABR amplitudes and DPOAE amplitudes in F344 males compared with females.

The authors have st 54 fullterm (Group ~~wb~~s, classified a to conceptional ageT order to verify the in e obtained data bitthweight was birthweight r&cd to conceptional age represents an important factor in the devdcpnent of auditory brainstem that ihe diJ; has ts be very cautious in SCA new 8 if they

Tinnitus is thought to be an auditory phenomenon resulting from spontaneous neuronal activity somewhere along the auditory pathway either in the peripheral or central auditory system. The neural abnormalities underlying tinnitus are largely unknown. This study analysis the auditory brainstem responses in normal hearing patients with tinnitus. This study consisted of 100 patients divided into two groups. Group I (Control): 50 Normal hearing patients without tinnitus. Group II (Study): 50 Normal hearing patients complaining of tinnitus. Both groups were submitted to full audiological history taking, otological examination, basic audiologic evaluation and Auditory brainstem responses (ABR) followed by calculation of the absolute latencies of wave I, III and V and interpeak latencies between waves I-III, III-V and I-V. In the study group 20 patients showed abnormal results in at least 1 of the 6 parameters evaluated. The results of absolute latencies of wave I, III and V showed significant prolongation, but the interpeak latencies of waves I-III, III-V and I-V were not significantly prolonged when compared with control group. Our study data showed that there are changes in the central pathways in the study group. The significance of these changes must be investigated with further audiological and neurological tests. We also understand that ABR has to be included in the work up of tinnitus patients whose hearing is within normal parameters.

NIHL caused by excessive noise exposed to cochlea. Curcumin is a medicine that has antioxidant effects. The purpose of this study was to look at the effect of curcumin on NIHL which was assessed with DPOAE, value and the expression of SOD and MDA. This research was conducted on 36 rats which were divided into 6 groups, group 1 was a control group, group 2 was a group receiving only noise treatment, groups 3 and 4 were the treatment group receiving curcumin after exposed to noise, groups 5 and 6 were preventive groups receiving curcumin starting from 14

Introduction Aminoglycoside, as an antimicrobial medication, also has side-effects on the inner ears, bringing about hearing disorders. Curcumin has been proven to be a strong scavenger against various reactive oxygen species (ROS), and the increase in ROS production is considered to play an important role in the process of hearing disorder. Objective To prove that curcumin is an effective antioxidant to prevent cochlear damage based on malondialdehyde (MDA) expression. Methods The present research used 32 Rattus norvegicus, of the Wistar lineage, randomly divided into 8 groups: negative control, ototoxic control (a single dose of 40 mg/ml of gentamicin via intratympanic injection), 2 groups submitted to ototoxic control + curcumin treatment (100 mg/kg, 200 mg/kg), 2 groups who iunderwent ototoxic control + curcumin treatment for 7 days, and two groups submitted to curcumin treatment as prevention for 3 days + ototoxic induction. Results The results showed that the lowest dosage of ...

The aim was to describe the outcome of neonatal hearing screening (NHS) and audiological diagnosis in neonates in the NICU. The sample was divided into Group I: neonates who underwent NHS in one step and Group II: neonates who underwent a test and retest NHS. NHS procedure was automated auditory brainstem response. NHS was performed in 82.1% of surviving neonates. For GI, referral rate was 18.6% and false-positive was 62.2% (normal hearing in the diagnostic stage). In GII, with retest, referral rate dropped to 4.1% and false-positive to 12.5%. Sensorineural hearing loss was found in 13.2% of infants and conductive in 26.4% of cases. There was one case of auditory neuropathy spectrum (1.9%). Dropout rate in whole process was 21.7% for GI and 24.03% for GII. We concluded that it was not possible to perform universal NHS in the studied sample or, in many cases, to apply it within the first month of life. Retest reduced failure and false-positive rate and did not increase evasion, indic...

To evaluate the feasibility of microRNAs (miR) in clinical use to fill in the gap of current methodology commonly used to test hearing impairment in MELAS patients. A literature review was performed using the following keywords, i.e., MELAS, Hearing Loss, Hearing Impairment, Temporal Bone, Otoacustic Emission (OTOAE), Auditory Brain Response (ABR), and microRNA. We reviewed the literature and focused on the aspect of the temporal bone, the results of electrophysiological tests in human clinical studies, and the use of miR for detecting lesions in the cochlea in patients with MELAS. In patients with MELAS, Spiral Ganglions (SG), stria vascularis (SV), and hair cells are damaged, and these damages affect in different ways various structures of the temporal bone. The function of these cells is typically investigated using OTOAE and ABR, but in patients with MELAS these tests provide inconsistent results, since OTOAE response is absent and ABR is normal. The normal ABR responses are une...

Tinnitus or ringing of the ears is a subjective phantom sensation necessitating behavioral models that objectively demonstrate the existence and quality of the tinnitus sensation. The gap detection test uses the acoustic startle response elicited by loud noise pulses and its gating or suppression by preceding sub-startling prepulses. Gaps in noise bands serve as prepulses, assuming that ongoing tinnitus masks the gap and results in impaired gap detection. This test has shown its reliability in rats, mice, and gerbils. No data exists for the guinea pig so far, although gap detection is similar across mammals and the acoustic startle response is a well-established tool in guinea pig studies of psychiatric disorders and in pharmacological studies. Here we investigated the startle behavior and prepulse inhibition (PPI) of the guinea pig and showed that guinea pigs have a reliable startle response that can be suppressed by 15 ms gaps embedded in narrow noise bands preceding the startle noise pulse. After recovery of auditory brainstem response (ABR) thresholds from a unilateral noise over-exposure centered at 7 kHz, guinea pigs showed diminished gap-induced reduction of the startle response in frequency bands between 8 and 18 kHz. This suggests the development of tinnitus in frequency regions that showed a temporary threshold shift (TTS) after noise over-exposure. Changes in discharge rate and synchrony, two neuronal correlates of tinnitus, should be reflected in altered ABR waveforms, which would be useful to objectively detect tinnitus and its localization to auditory brainstem structures. Therefore, we analyzed latencies and amplitudes of the first five ABR waves at suprathreshold sound intensities and correlated ABR abnormalities with the results of the behavioral tinnitus testing. Early ABR wave amplitudes up to N3 were increased for animals with tinnitus possibly stemming from hyperactivity and hypersynchrony underlying the tinnitus percept. Animals that did not develop tinnitus after noise exposure showed the opposite effect, a decrease in wave amplitudes for the later waves P4-P5. Changes in latencies were only observed in tinnitus animals, which showed increased latencies. Thus, tinnitus-induced changes in the discharge activity of the auditory nerve and central auditory nuclei are represented in the ABR.

In Bilateria, many axons cross the midline of the central nervous system, forming well-defined commissures. Whereas in mammals the functions of commissures in the forebrain and in the visual system are well established, functions at other axial levels are less clearly understood. Here, we have dissected the function of several hindbrain commissures using genetic methods. By taking advantage of multiple Cre transgenic lines, we have induced site-specific deletions of the Robo3 receptor. These lines developed with the disruption of specific commissures in the sensory, motor, and sensorimotor systems, resulting in severe and permanent functional deficits. We show that mice with severely reduced commissures in rhombomeres 5 and 3 have abnormal lateral eye movements and auditory brainstem responses, respectively, whereas mice with a primarily uncrossed climbing fiber/Purkinje cell projection are strongly ataxic. Surprisingly, although rerouted axons remain ipsilateral, they still project to their appropriate neuronal targets. Moreover, some Cre;Robo3 lines represent potential models that can be used to study human syndromes, including horizontal gaze palsy with progressive scoliosis (HGPPS). To our knowledge, this study is one of the first to link defects in commissural axon guidance with specific cellular and behavioral phenotypes.

Introduction: Cerebrovascular comorbidity factors (CCF) namely hypertension (HT) and hypercholesterolemia (HC) has been associated individually to the abnormalities seen in absolute peak latencies (APL) and inter-peak latencies (IPL) of the auditory brainstem response (ABR). HT effects the upper brainstem at lower click stimulus rate and HC effects the lower brainstem at higher click stimulus rate. However, concomitant effect of HT and HC on ABR parameters are inadequate. Material and Methods: Total 200 (age 40 60 years) non-diabetic subjects were measured for total cholesterol (TC) and blood pressure (BP). They were divided equally into four groups based on the reported measures (HC for TC &gt; 200mg/dl; and HT for BP&gt; 140/90 mmHg) as Group A (normal TC and BP), B (HC, normal BP), C (HT, normal TC), and D (HT, HC). ABR at low click stimulus were then recorded from subjects, and APL and IPL of groups B, C and D were compared with group A. Results: Group Cvs A: Significant increas...

Purpose: To study the Electric Auditory Brainstem Response (EABR) measures and their relation to speech perception outcomes-both in quiet and noise-and to the phonological tests. Patients and Methods: Twenty-six unilaterally implanted children were subjected to EABR recording. EABR was recorded from one apical electrode E21 (A) and one basal electrode E2 (B). Word recognition scores (WRS), Bamford-Kowel Bench speech in noise (BKB-SIN test), and phonological assessment [auditory level, speech intelligibility index, and language test] were done. Results: This research showed statistically significant better EABR responses recorded from the apical electrodes (A) compared to the basal ones (B) as regards amplitude growth function (AGF) slopes, maximum amplitudes, thresholds, and latencies. Significant positive correlations were reported between both EABR slopes and maximum amplitudes and the WRs; however, significant negative correlations were found between EABR slopes and maximum amplitude measurements and the dB SNR loss of BKB-SIN values. Furthermore, the AGF slopes had significant correlations with the auditory level and the speech intelligibility index. Conclusion: EABR AGF slopes and maximum amplitudes were both correlated with speech recognition in quiet and in noise and were correlated with phonological assessment. These encouraging findings can be used for CI outcome prediction and can help clinicians provide optimal services to pediatric CI recipients and facilitate realistic expectations among caregivers.

The visual evoked potentials technique records the cerebral bioelectric activity generated by light stimulation. Evoked potentials is a good method of assessing the electrical response of the brain to different stimuli and has been used extensively in the study of brain disturbances. We registered VEP on 18 hyperthyroid and 18 hypothyroid patients, without other endocrine, metabolic, ophthalmologic or neurological illnesses, the 2 groups having practically identical ages, but sex repartition, illness age and treatment duration being statistically different (p[0.001). Hormonal, radiological, biochemical dosages and physiological paraclinic determinations were performed on all 36 subjects, through classical methods, and VEP recordings, with a 4 channel polygraph through pattern reversal stimulation (1 Hz), measuring all parameters (latency, amplitude, duration, surface, steepness etc.) of N75 and P100 waves. Between groups, the recorded hormone levels and other recordings showed great...

Age-related hearing loss (ARHL) is the most common sensory impairment mainly caused by degeneration of sensory hair cells in the cochlea with no causal medical treatment available. Auditory function and sensory hair cell survival critically depend on the Kv7.4 (KCNQ4) channel, a voltage-gated potassium channel expressed in outer hair cells (OHCs), with its impaired function or reduced activity previously associated with ARHL. Here, we investigated the effect of a potent small-molecule Kv7.4 agonist on ARHL in the senescence-accelerated mouse prone 8 (SAMP8) model. For the first time in vivo, we show that Kv7.4 activation can significantly reduce age-related threshold shifts of auditory brainstem responses as well as OHC loss in the SAMP8 model. Pharmacological activation of Kv7.4 thus holds great potential as a therapeutic approach for ARHL as well as other hearing impairments related to Kv7.4 function.

People are increasingly exposed to environmental noise through the cumulation of occupational and recreational activities, which is considered harmless to the auditory system, if the sound intensity remains &lt;80 dB. However, recent evidence of noise-induced peripheral synaptic damage and central reorganizations in the auditory cortex, despite normal audiometry results, has cast doubt on the innocuousness of lifetime exposure to environmental noise. We addressed this issue by exposing adult rats to realistic and nontraumatic environmental noise, within the daily permissible noise exposure limit for humans (80 dB sound pressure level, 8 h/day) for between 3 and 18 months. We found that temporary hearing loss could be detected after 6 months of daily exposure, without leading to permanent hearing loss or to missing synaptic ribbons in cochlear hair cells. The degraded temporal representation of sounds in the auditory cortex after 18 months of exposure was very different from the effe...

Patients with neurofibromatosis type 2 (NF2) report that their greatest problem is deafness. 1 If a patient is due to be rendered bilaterally deaf as is eventually the case in NF2 then the choice of hearing rehabilitation lies between a cochlear implant and an auditory brainstem implant (ABI). It is a usual practice to use an ABI in the NF2 population as preserving the cochlear nerve during NF2-related vestibular schwannoma (VS) removal is difficult, and anatomical preservation does not guarantee functional preservation. 2 Keywords ► cochlear nerve monitoring ► neurofibromatosis type 2 ► hearing preservation ► EABR

The safety of implanting a titanium microactuator into the lateral wall of cat scala tympani was assessed by comparing preoperative and postoperative auditory brainstem response (ABR) thresholds for 1 to 3 months. Background: The safety of directly stimulating cochlear perilymph with an implantable hearing system requires maintaining preoperative hearing levels. This cat study is an essential step in the development of the next generation of fully implantable hearing devices for humans. Methods: Following GLP surgical standards, a 1-mm cochleostomy was drilled into the lateral wall of the scala tympani, and a nonfunctioning titanium anchor/microactuator assembly was inserted in 8 cats. The scala media was damaged in the 1 cat. ABR thresholds with click and 4-and 8-kHz stimuli were measured preoperatively and compared with postoperative thresholds at 1, 2, and 3 months. Nonimplanted ear thresholds were also measured to establish statistical significance for threshold shifts (928.4 dB). Two audiologists independently interpreted thresholds. Results: Postoperatively, 7 cats implanted in the scala tympani demonstrated no significant ABR threshold shift for click stimulus; one shifted ABR thresholds to 4-and 8-kHz stimuli. The eighth cat, with surgical damage to the scala media, maintained stable click threshold but had a significant shift to 4-and 8-kHz stimuli. This cat study provides no evidence of worsening hearing thresholds after fenestration of the scala tympani and insertion of a titanium anchor/microactuator, provided there is no surgical trauma to the scala media and the implanted device is securely anchored in the cochleostomy. These 2 issues have been resolved in the development of a fully implantable hearing system for humans. The long-term hearing stability (combined with histologic studies) reaffirm that the microactuator is well tolerated by the cat cochlea.

Background: There are about 1.6 billion GSM cellular phones in use throughout the world today. Numerous papers have reported various biological effects in humans exposed to electromagnetic fields emitted by mobile phones. The aim of the present study was to advance our understanding of potential adverse effects of the GSM mobile phones on the human hearing system. Methods: Auditory Brainstem Response (ABR) was recorded with three non-polarizing Ag-AgCl scalp electrodes in thirty young and healthy volunteers (age 18-26 years) with normal hearing. ABR data were collected before, and immediately after a 10 minute exposure to 900 MHz pulsed electromagnetic field (EMF) emitted by a commercial Nokia 6310 mobile phone. Fifteen subjects were exposed to genuine EMF and fifteen to sham EMF in a double blind and counterbalanced order. Possible effects of irradiation was analyzed by comparing the latency of ABR waves I, III and V before and after genuine/sham EMF exposure. Results: Paired sample t-test was conducted for statistical analysis. Results revealed no significant differences in the latency of ABR waves I, III and V before and after 10 minutes of genuine/sham EMF exposure. The present results suggest that, in our experimental conditions, a single 10 minute exposure of 900 MHz EMF emitted by a commercial mobile phone does not produce measurable immediate effects in the latency of auditory brainstem waves I, III and V.

GM-1 ganglioside (GM-1), a glycosphingolipid, is embedded in the lipid layer of neuronal membranes and is one of the neuroprotective agents. To the best of our knowledge, the role of GM-1 has never been examined in hair cell injury. The purpose of this study was therefore to evaluate the effects of GM-1 on acoustic injury of the cochlea. Mice were exposed to 4-kHz pure tone of 128 dB SPL (sound pressure level) for 4 hours. GM-1 was intraperitoneally administered immediately before the onset of acoustic overexposure. The threshold shift of the auditory brainstem response (ABR) and hair cell loss were then evaluated 2 weeks after acoustic overexposure. Immunostaining for 4-hydroxynonenal (4-HNE), indicative of lipid peroxidation, was also examined in animals subjected to acoustic overexposure. GM-1 treatment significantly decreased the ABR threshold shifts and hair cell loss after acoustic overexposure. And immunostaining for 4-HNE was reduced by GM-1 treatment. These findings suggest that GM-1 is involved in the protection of the cochlea against acoustic injury through inhibiting lipid

The absence of functional outer hair cells is a component of several forms of hereditary hearing impairment, including Usher syndrome, the most common cause of concurrent hearing and vision loss. Antisense oligonucleotide (ASO) treatment of mice with the human Usher mutation, Ush1c c.216G9A, corrects gene expression and significantly improves hearing, as measured by auditory-evoked brainstem responses (ABRs), as well as inner and outer hair cell (IHC and OHC) bundle morphology. However, it is not clear whether the improvement in hearing achieved by ASO treatment involves the functional rescue of outer hair cells. Here, we show that Ush1c c.216AA mice lack OHC function as evidenced by the absence of distortion product otoacoustic emissions (DPOAEs) in response to low-, mid-, and highfrequency tone pairs. This OHC deficit is rescued by treatment with an ASO that corrects expression of Ush1c c.216G9A. Interestingly, although rescue of inner hairs cells, as measured by ABR, is achieved by ASO treatment as late as 7 days after birth, rescue of outer hair cells, measured by DPOAE, requires treatment before post-natal day 5. These results suggest that ASO-mediated rescue of both IHC and OHC function is age dependent and that the treatment window is different for the different cell types. The timing of treatment for congenital hearing disorders is of critical importance for the development of drugs such ASO-29 for hearing rescue.

Objective: NIHL is a common problem, and steroids are the most effective treatment option. In this study, we aimed to evaluate the protective effects of the synthetic adrenocorticotropic hormone (ACTH) analogues, which induce endogenous steroid secretion, against noise-induced hearing loss (NIHL) and to compare their effectiveness with that of steroid treatment. Methods: Twenty-four male Sprague-Dawley albino rats were divided into four subgroups as follows: group 1 (n = 6) control, group 2 (n = 6) saline, group 3 (n = 6) dexamethasone (2 mg/kg/ day intramuscularly [IM]), group 4 (n = 6) ACTH analogue (0,4 mg/kg/day IM), respectively. Three groups (groups 2-4) were exposed to white noise (105 dB SPL, 12 h). All the rats were evaluated for hearing thresholds of 10 kHz, 20 kHz, and 32 kHz via acoustic brainstem responses (ABR) measurement. After the basal threshold measurements, measurements were repeated immediately after the noise and on day 7 and day 21. Results: Both steroid and ACTH analogue groups showed significantly better hearing outcomes than the saline group on day 7 (p < 0.001) and day 21 (p < 0.001) after the noise exposure. No superior treatment effect was demonstrated in either the steroid or ACTH analogue group. None of the related intervention groups reached the basal hearing thresholds. Conclusion: Steroids were effective drugs for the treatment of NIHL. ACTH analogues also demonstrated promising therapeutic effects for NIHL. Further studies to establish ACTH analogues as an alternative NIHL treatment option to steroids are needed.

Deteriorated speech comprehension is a common manifestation of the age-related decline of auditory functions (presbycusis). It could be assumed that when presbycusis is accompanied by tinnitus, general hearing functions, and particularly comprehension of speech in quiet and speech in noise (SIN), will be significantly affected. In this study, speech comprehension ability and other parameters of auditory function were assessed in elderly subjects with (T, n = 25) and without (NT, n = 26) tinnitus, aiming for examination of both peripheral and central auditory processing. Apart from high-frequency audiograms in quiet and in background noise, speech recognition thresholds in silence or in competitive babble noise, and the ability to understand temporally gated speech (GS), we measured also sensitivity to frequency modulation (FM) and interaural delay, gap detection thresholds (GDT), or the difference limens of intensity. The results show that in elderly participants matched by age (mean ages around 68 years), cognitive status (median MoCA scores around 27), and hearing thresholds [median pure-tone averages (PTA) around 16 dB hearing loss (HL)], tinnitus per se has little influence on speech comprehension. The tinnitus patients also show similar GDT, sensitivity to interaural intensity difference, and sensitivity to FM as the NT subjects. Despite these similarities, nevertheless, significant differences in auditory processing have been found in the tinnitus participants: a worse ability to detect tones in noise, a higher sensitivity to intensity changes, and a higher sensitivity to interaural time differences. Additional correlation analyses further revealed that speech comprehension in the T subjects is dependent on the sensitivity to temporal modulation and interaural time delay (ITD), while these correlations are weak Abbreviations: DLI noise , difference limen for intensity of white noise bursts; DLI tone , difference limen for intensity of a tone in noise; FM, frequency modulation; GDT, detection thresholds of gap in white noise; GS, recognition thresholds of temporally gated speech; ILD, interaural level difference; ITD, interaural time delay; NT, subjects without tinnitus; PTA, pure tone average; PTA noise , pure tone average in noise; PTAw, wide-range pure-tone average; PTAw noise , wide-range pure tone average in noise; SIN, speech recognition thresholds in competitive babble noise; SNR, signal to noise ratio; SRS, speech recognition threshold in silence; T, subjects with tinnitus; T1, tinnitus patients with the THI score ''slight''; T2, tinnitus patients with the THI score worse than ''slight''; THI, Tinnitus Handicap Inventory questionnaire.

Voltage-gated Ca 2+ channels (VGCCs) play key roles in auditory perception and information processing within the inner ear and brainstem. Pharmacological inhibition of low voltage-activated (LVA) T-type Ca 2+ channels is related to both age-and noise induced hearing loss in experimental animals and may represent a promising approach to the treatment of auditory impairment of various etiologies. Within the LVA Ca 2+ channel subgroup, Ca v 3.2 is the most prominently expressed T-type channel entity in the cochlea and auditory brainstem. Thus, we performed a complete gender specific click and tone burst based auditory brainstem response (ABR) analysis of Ca v 3.2 +/-and Ca v 3.2 -/-mice, including i.a. temporal progression in hearing loss, amplitude growth function and wave latency analysis as well as a cochlear qPCR based evaluation of other VGCCs transcripts. Our results, based on a self-programmed automated wavelet approach, demonstrate that both heterozygous and Ca v 3.2 null mutant mice exhibit age-dependent increases in hearing thresholds at 5 months of age. In addition, complex alterations in W I-IV amplitudes and latencies were detected that were not attributable to alterations in the expression of other VGCCs in the auditory tract. Our results clearly demonstrate the important physiological role of Ca v 3.2 VGCCs in the spatiotemporal organization of auditory processing in young adult mice and suggest potential pharmacological targets for interventions in the future.

There are many people who have been involved in shaping my career. I would like to first thank Dr. Charles Berlin, a great mentor, teacher, boss, and friend. Your enthusiasm and love for audiology is so inspiring. I would also like to thank two great teachers, mentors and friends, Dr. Jane Collins and Dr. Lee Mendoza who have incredible wisdom and insight. I would like to thank all of the members of my committee. Drs. Hugh Buckingham, Paul Hoffman, Jan Norris, and Alan Baumeister were helpful in getting me through this final process. Dr. Jack Cullen, my committee chairperson, has been a great influence. I thank you for your tremendous support and patience. I am very fortunate to have been one of your students. I would especially like to thank Dr. Linda Hood for her years of support and guiding force. I learned so much working as your research assistant at Kresge Research Laboratory. You are an incredible role model. Thank you for giving your valuable time to help me finish this endeavor. I am not sure I could have finished this project without the support of Dr. Jerry Cranford, my department chair. Thank you for your time, support and your belief in me. You are a terrific boss! I would also like to thank Dr. Stephen Leierer for his help with the statistical analysis for this project. In addition, I would also like to thank him for his encouraging words that came at the right times. I would like to thank the faculty in the Department of Communication Sciences at the LSU Health Sciences Center in New Orleans for their support. Lastly, I am very thankful for the promise in Philippians 4:13.

The aim of this study was to analyze the changes in the auditory function in infants with perinatal brain injury (PBI) and severe to deep hearing loss with early use of hearing aids (HA). Method: 378 infants with PBI were studied with Otoacoustic Emissions (OAEs), Brainstem Auditory Evoked Potentials (BAEPs) and Auditory Steady State Responses (ASSRs) in natural sleep for determining auditory threshold. 13 infants had bilateral sensorineural severe to deep hearing loss. 6 (46.2%) were premature and 7 (53.8%) full-term. The digital HA was adapted in right ear not later than 6 months of age, with an average time of 4 to 6 hours per day. The BAEP and ASSR were performed two times, before 6 months and 12 months old. Statistical analysis was carried out with t-test for related samples. Results: The initial threshold of right ear BAEPs was 81.1 dB and 71.3 dB (p = 0.030) after the use of HA. In the left side, used as control, the initial threshold was 81.4 dB and 81.0 dB after the use of HA (p= 0.225). The threshold of right ear ASSR in frequency of 4000 Hz in was 89 dB and 77 dB (p = 0.013) after the use of HA, the other frequencies of right side and all frequencies of left ear showed no difference (p = 0.846). Conclusions: We conclude that the early use of HA by six months decrease the auditory threshold of BAEPs and the 4000 Hz frequency of ASSRs.

Survivors of childhood bacterial meningitis (BM) often develop hearing impairment (HI). In low- and middle-income countries (LMICs), BM continues to be a significant cause of hearing disability. We assessed hearing among BM survivors using auditory steady-state responses (ASSR), providing frequency-specific estimated audiograms, and examined whether ASSR would provide a greater understanding of BM-induced HI. Survivors from two prospective BM trials (ISRCTN62824827; NCT01540838) from Luanda Children’s Hospital were examined in a follow-up visit with a median duration of 26 months after BM. The hearing of 50 BM survivors and 19 control children was evaluated using ASSR and auditory brainstem response (ABR) after interview and neurological and otorhinolaryngological examinations. The median age of survivors was 80 (IQR 86) months. We diagnosed HI (better ear hearing ≥ 26 dB) in 9/50 (18%) children. Five of the fifty survivors (10%) and 14/100 ears (14%) had profound HI (&gt;80 dB). Se...

Background: Hearing loss from childhood bacterial meningitis is believed to develop early and have little tendency for recovery. We performed serial hearing evaluations in a large number of children with bacterial meningitis in Luanda, Angola to clarify if, and how often, the result changed. Methods: Children with confirmed bacterial meningitis and hearing evaluations on admission, day 7 of treatment and the follow-up visit formed the study group. Hearing was tested by auditory brainstem response audiometry using stimuli of 40 dB, 60 dB and 80 dB. Threshold changes are described between the composite levels of 40/60 dB and 80/>80 dB. Results. In all, 235 ears were tested. While the ≤60 dB and ≥80 dB levels were maintained through all 3 examinations in 54% and 5% of ears, respectively, changes occurred in 41%. Deterioration from the ≤60 dB level to ≥80 dB was found in 10% of the ears transiently and in 7% permanently. Improvement from the ≥80 dB level to ≤60 dB occurred in 22% of the ears. Half of the ears with ≥80 dB impairment at the follow-up visit arrived with this finding; the others lost hearing later. Maintaining the ≤60 dB level throughout was associated with milder disease (P = 0.003), fewer convulsions (P < 0.0001) and older age (P = 0.009). Conclusions: Almost half of the ears showed threshold changes after admission during recovery from bacterial meningitis, most frequently improvement of initially severely impaired hearing, but some normal ears or with moderate impairment became severely impaired.

The performance of auditory steady state response (ASSR) in threshold testing when recorded ipsilaterally and contralaterally, as well as at low and high modulation frequencies (MFs), has not been systematically studied. To verify the influences of mode of recording (ipsilateral vs. contralateral) and modulation frequency (40Hz vs. 90Hz) on ASSR thresholds. Fifteen female and 14 male subjects (aged 18-30 years) with normal hearing bilaterally were studied. Narrow-band CE-chirp(®) stimuli (centerd at 500, 1000, 2000, and 4000Hz) modulated at 40 and 90Hz MFs were presented to the participants&#39; right ear. The ASSR thresholds were then recorded at each test frequency in both ipsilateral and contralateral channels. Due to pronounced interaction effects between mode of recording and MF (p&lt;0.05 by two-way repeated measures ANOVA), mean ASSR thresholds were then compared among four conditions (ipsi-40Hz, ipsi-90Hz, contra-40Hz, and contra-90Hz) using one-way repeated measures ANOVA. ...

Asymmetric sensorineural hearing loss is the main early symptom of retrocochlear lesions, hence its importance in screening for vestibular schwannomas. Currently, there is no consensus regarding its definition. The objective was to identify the audiometric pattern that would serve as a predictor for vestibular schwannoma in patients with asymmetric hearing loss. A cross-sectional study was conducted that included patients with asymmetric hearing loss attending a secondary care center and a tertiary care center. Clinical, audiometric and imaging (MRI with gadolinium) variables were collected. Asymmetric hearing loss was defined as a difference of 15 dB in one or more frequencies between both ears. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of different audiometric patterns were analyzed. A total of 107 patients were studied and divided into two groups: group 1 without vestibular schwannoma (n=98); and group 2 with vestibular schwannoma (n=9). No significant difference in demographic characteristics or audiometric patterns was found in patients with and without vestibular schwannoma. The audiometric pattern with the best sensitivity as a screening test was a difference >20 dB in the 4,000 Hz frequency, with a sensitivity of 77.78%, specificity of 30.61%, PPV of 8.33%, NPV of 93.75% and accuracy of 34.50%. The audiometric pattern with the best results was a difference >20 dB in the 4,000 Hz frequency range; however, patients with asymmetric hearing loss could not be differentiated from patients with retrocochlear lesions based only on audiometry. Asymmetrical hearing loss must be studied with MRI.

Asymmetric sensorineural hearing loss is the main early symptom of retrocochlear lesions, hence its importance in screening for vestibular schwannomas. Currently, there is no consensus regarding its definition. The objective was to identify the audiometric pattern that would serve as a predictor for vestibular schwannoma in patients with asymmetric hearing loss. A cross-sectional study was conducted that included patients with asymmetric hearing loss attending a secondary care center and a tertiary care center. Clinical, audiometric and imaging (MRI with gadolinium) variables were collected. Asymmetric hearing loss was defined as a difference of 15 dB in one or more frequencies between both ears. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of different audiometric patterns were analyzed. A total of 107 patients were studied and divided into two groups: group 1 without vestibular schwannoma (n=98); and group 2 with vestibular schwannoma (n=9). No significant difference in demographic characteristics or audiometric patterns was found in patients with and without vestibular schwannoma. The audiometric pattern with the best sensitivity as a screening test was a difference >20 dB in the 4,000 Hz frequency, with a sensitivity of 77.78%, specificity of 30.61%, PPV of 8.33%, NPV of 93.75% and accuracy of 34.50%. The audiometric pattern with the best results was a difference >20 dB in the 4,000 Hz frequency range; however, patients with asymmetric hearing loss could not be differentiated from patients with retrocochlear lesions based only on audiometry. Asymmetrical hearing loss must be studied with MRI.

Ototoxicity is an adverse side effect of numerous therapeutic agents (aminoglycoside antibiotics, blood chelating agents, diuretics and oncologic drugs) used in treatment of both adult and pediatric patients. Recently, there has been increasing interest in using the auditory brainstem response (ABR) to detect both short-term effects of ototoxicity in adults and long-term effects of drug administration on neonates and children. Since click ABRs have relatively poor frequency selectivity they best approximate the pure-tone hearing threshold in the 2000-4000 Hz frequency range. Hearing loss above or below that frequency range can be present without producing significant abnormalities in the ABR waveform parameters. Frequency-specific ABRs can be obtained using the derived response technique. The purpose of this study was to investigate early cisplatin ototoxicity using both the broadband click and derived ABR and to monitor progressive hearing Ioss with repeated drug trials in 18 patients studied over a 2-year period. ABRs were obtained serially prior to and following intravenous administration of cisplatin.

Temperature sensitive copolymer systems were previously studied using modified diffusion cells in vitro for intratympanic injection, and the PLGA-PEG-PLGA copolymer systems were found to provide sustained drug delivery for several days. The objectives of the present study were to assess the safety of PLGA-PEG-PLGA copolymers in intratympanic injection in guinea pigs in vivo and to determine the effects of additives glycerol and poloxamer in PLGA-PEG-PLGA upon drug release in the diffusion cells in vitro for sustained inner ear drug delivery. In the experiments, the safety of PLGA-PEG-PLGA copolymers to inner ear was evaluated using auditory brainstem response (ABR). The effects of the additives upon drug release from PLGA-PEG-PLGA hydrogel were investigated in the modified Franz diffusion cells in vitro with cidofovir as the model drug. The phase transition temperatures of the PLGA-PEG-PLGA copolymers in the presence of the additives were also determined. In the ABR safety study, the PLGA-PEG-PLGA copolymer alone did not affect hearing when delivered at 0.05-mL dose but caused hearing loss after 0.1-mL injection. In the drug release study, the incorporation of the bioadhesive additive, poloxamer, in the PLGA-PEG-PLGA formulations was found to decrease the rate of drug release whereas the increase in the concentration of the humectant additive, glycerol, provided the opposite effect. In summary, the PLGA-PEG-PLGA copolymer did not show toxicity to the inner ear at the 0.05-mL dose and could provide sustained release that could be controlled by using the additives for inner ear applications.

The brainstem auditory evoked response (BAER) was recorded from 20 dogs, l0 exhibiting vestibular deficit, and l0 presented with a history of seizures. Two dogs exhibited both types of signs. Abnormalities of the BAER, prolonged interwave latency, were seen in 8 of the I0 animals with vestibular problems, and in 7 of the i0 animals with seizure history. Several different diagnosis were associated with BAER abnormalities in both groups of animals. In 55.5% of the cases exhibiting abnormalities of the BAER, postmortem evidence of brainstem pathology was not detected. The electroencephalogram (BEG) was normal in three instances of abnormalities of the BAER. The BAER was normal in three dogs with abnormalities of the BEG. The BAER is presented as a useful diagnostic tool for brain lesions in animals with vestibular deficit and seizure his, tory, but appears most useful when used in conjuction with the EEG. Correlations of abnormalities of the BAER and clinical course of disease are discussed. s

Background: A negative potential is occasionally recorded in humans and animals with profound deafness during brainstem auditory evoked potential (BAER) tests if loud intensities are used. This acoustically evoked short latency negative response (ASNR) is hypothesized to be of saccular origin. The sensitivity to sound of vestibular end organs is also used to produce vestibular evoked myogenic potentials (VEMP), a test that evaluates vestibular function. The same saccular origin is accepted also for VEMP. Case presentation: A neutered male white domestic short hair cat presented with profound deafness and an ASNR in the left ear during BAER test performed when he was 8 months old. BAER tracings were substantially unchanged at the age of 12 years, immediately before euthanasia that was requested by the owner for the presence of an unrelated neoplastic disorder. The cat underwent a complete post-mortem necropsy including histopathology of the middle and inner ears. Histopathologic results confirmed the presence of a cochleosaccular degeneration of the left ear while the cochlea and sacculus of the right ear and the utriculus and semicircular canals of both ears were histologically normal. Conclusions: This case report describes the auditory and histopathologic findings of a cat that showed an ASNR during BAER test despite the presence of cochleosaccular deafness. These results confirm that a saccular origin for the ASNR in this case, and in general in cats and dogs with congenital deafness associated with white pigmentation, is improbable. The hypothesis that the sacculus is the vestibular end organ responsible for the generation of the ASNR and VEMP in humans comes mainly from animal studies. The findings in this report may change the clinical interpretation of the results of BAER and VEMP not only in companion animals, but in humans as well.

Many treatments for clogged tympanostomy tubes (TTs) have been proposed, but none have met scientific rigor for safety and efficacy, including the popular empirical use of ototopical antibiotic drops. Dornase alfa, a recombinant molecule with the unique property of cleaving DNA, may be ideal in treating clogged TTs because both middle-ear effusion and the plug are abundant with DNA. To investigate the ototoxic effects of dornase alfa in a chinchilla model and its efficacy in a clinical trial in children with clogged TTs. The safety profiles of dornase alfa (full-strength and 1:10 strength) were evaluated in chinchilla middle ears using serial auditory brainstem response. The efficacy of ototopical dornase alfa (full-strength) was evaluated in children with clogged TTs in a prospective, single-blind randomized clinical trial. The animal study included 21 chinchillas and was conducted at Loma Linda University, Loma Linda, California, and the clinical trial was conducted at Children&#3...

Detection of a brief tonal signal at the beginning of a longer masking noise is difficult, but it becomes easier when the onset of the signal is delayed. This phenomenon is known as overshoot or temporal effect. Our study investigates the impact of the auditory efferent nerves (AENs) function on the auditory electrophysiological overshoot, further introducing an objective tool examining one of the AENs performances. Therefore, the effect and the trend of changes induced by low-and high-frequency stimuli on electrophysiological overshoot were studied in different delay onset times (DOTs) between the signal and the noise before and after dissecting the AENs. Methods: Right internal auditory canals were exposed in 16 young male guinea pigs weighing 250 to 350 g. The inferior and posterior vestibular nerves known to carry AENs were transected in half of the subjects. Then, the ABR waveforms were recorded at 16 and 8 kHz tone burst stimuli at 0, 30, 60, and 100 ms DOTs relative to wideband noise. The latency values of auditory brainstem response (ABR) waves I and III were compared among the different DOTs and 5 signal-to-noise ratios (SNRs) before and after the surgery. Results: By increasing DOTs, ABR waves I and III latency decreased in the control group before and after the surgery and in the case group before surgery at 16 kHz. However, the observed overshoot-like effect disappeared after the surgery in the case group. The wave's latency I and III increased from 0 to 30 ms, remained approximately constant from 30 to 60 ms, and then decreased toward 100 ms DOTs. However, none of the measurements at 8 kHz before and after surgery in both groups showed an overshoot effect. Conclusion: Using the ABR paradigm, the overshoot phenomenon disappeared after the transection of AENs. The results confirmed the role of the efferent system in auditory overshooting. Therefore, an objective tool to measure auditory efferent function is provided.

Aim: To protect hearing in an experimental model of cochlear implantation by the application of dexamethasone to the round window prior to surgery. The present study examined the dosage and timing relationships required to optimise the hearing protection. Methods: Dexamethasone or saline (control) was absorbed into a pledget of the carboxymethylcellulose and hyaluronic acid and applied to the round window of the guinea pig prior to cochlear implantation. The treatment groups were 2% w/v dexamethasone for 30, 60 and 120 min; 20% dexamethasone applied for 30 min. Auditory sensitivity was determined pre-operatively, and at 1 week after surgery, with puretone auditory brainstem response audiometry (2-32 kHz). Cochlear implantation was performed via a cochleostomy drilled into the basal turn of the cochlea, into which a miniature cochlear implant dummy electrode was inserted using soft-surgery techniques. Results: ABR thresholds were elevated after cochlear implantation, maximally at 32 kHz and to a lesser extent at lower frequencies. Thresholds were less elevated after dexamethasone treatment, and the hearing protection improved when 2% dexamethasone was applied to the round window for longer periods of time prior to implantation. The time that dexamethasone need be applied to achieve hearing protection could be reduced by increasing the concentration of steroid, with a 20% application for 30 min achieving similar levels of protection to a 60 min application of 2% dexamethasone. Conclusions: Hearing protection is improved by increasing the time that dexamethasone is applied to the round window prior to cochlear implantation, and the waiting time can be reduced by increasing the steroid concentration. These results suggest that the diffusion dexamethasone through the cochlea is the prime determinant of the extent of hearing protection.