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.

Quick Estimation of Minimum Hearing Levels Using a Binaural Multifrequency Stimulus Paradigm: Proof of Concept.

OBJECTIVES: Objective estimation of minimum hearing levels using auditory brainstem responses (ABRs) elicited by single frequency tone-bursts presented monaurally is currently considered the gold standard. However, the data acquisition time to estimate thresholds (for both ears across four audiometric frequencies) using this method usually exceeds the sleep time (ranging between 35 and 49 minutes) in infants below 4 months, thus providing incomplete information of hearing status which in turn delays timely clinical intervention. Alternate approaches using faster rate, or tone-burst trains have not been readily accepted due to additional hardware and software requirements. We propose here a novel binaural multifrequency stimulation paradigm wherein several stimuli of different frequencies are presented binaurally in an interleaved manner. The rationale here is that the proposed paradigm will increase acquisition efficiency, significantly reduce test time, and improve accuracy by incorporating an automatic wave V detection algorithm. It is important to note that this paradigm can be easily implemented in most commercial ABR systems currently used by most clinicians. DESIGN: Using this binaural multifrequency paradigm, ear specific ABRs were recorded in 30 normal-hearing young adults to both tone-bursts, and narrow-band (NB) iChirps at 500, 1000, 2000, and 4000 Hz. Comparison of ABRs elicited by tone-bursts and narrow-band chirps allowed us to determine if NB iChirps elicited a more robust wave V component compared with the tone-bursts. ABR data were characterized by measures of minimum hearing levels; wave V amplitude; and response detectability for two electrode configurations (high forehead-C7; and high forehead-linked mastoids). RESULTS: Consistent with the research literature, wave V response amplitudes were relatively more robust for NB iChirp stimuli compared with tone-burst stimuli. The easier identification and better detectability of wave V for the NB iChirps at lower stimulus levels contributed to their better thresholds compared with tone-burst elicited responses. It is important to note that binaural multifrequency hearing levels close to minimum hearing levels were determined in approximately 22 minutes using this paradigm-appreciably quicker than the 45 to 60 minutes or longer time required for threshold determination using the conventional single frequency method. CONCLUSIONS: Our novel and simple paradigm using either NB iChirps or tone-bursts provides a reliable method to rapidly estimate the minimum hearing levels across audiometric frequencies for both ears. Incorporation of an automatic wave V detection algorithm increases objectivity and further reduce test time and facilitate early hearing identification and intervention.

Auditory brainstem, middle and late latency responses to short gaps in noise at different presentation rates.

OBJECTIVE: The effects of rate on auditory-evoked potentials (AEP) to short noise gaps (12 ms) recorded at high sampling rates using wide-band filters were investigated. DESIGN: Auditory brainstem (ABR), middle latency (MLR), late latency (LLR) and steady-state (ASSR) responses were simultaneously recorded in adult subjects at four gap rates (0.5, 1, 5 and 40 Hz). Major components (V, Na, Pa, Nb, Pb, N1 and P2) were identified at each rate and analysed for latency/amplitude characteristics. Gap responses at 40 Hz were recovered from Quasi-ASSRs (QASSR) using the CLAD deconvolution method. STUDY SAMPLE: Fourteen right ears of young normal hearing subjects were tested. RESULTS: All major components were present in all subjects at 1 Hz. P1 (P50) appeared as a low-pass filtered component of Pa and Pb waves. At higher rates, N1 and P2 disappeared completely while major ABR-MLR components were identified. Peak latencies were mostly determined by noise onsets slightly delayed by offset responses. CONCLUSIONS: Major AEP components can be recorded to short gaps at 1 Hz using high sampling rates and wide-band filters. At higher rates, only ABR and MLRs can be recorded. Such simultaneous recordings may provide a complete assessment of temporal resolution and processing at different levels of auditory pathways.

Fast Click Rate Electrocochleography and Auditory Brainstem Response in Normal-Hearing Adults Using Continuous Loop Averaging Deconvolution.

OBJECTIVES: Using the continuous loop averaging deconvolution (CLAD) technique for conventional electrocochleography (ECochG) and auditory brainstem response (ABR) recordings, the effects of testing at high stimulus rates may have the potential to diagnose disorders of the inner ear and auditory nerve. First, a body of normative data using the CLAD technique must be established. DESIGN: Extratympanic click ECochG and ABR to seven stimulus rates using CLAD were measured simultaneously from a tympanic membrane electrode and surface electrodes on the forehead and mastoid of 42 healthy individuals. RESULTS: Results showed that the compound action potential (AP) of the ECochG and waves I, III, and V of the ABR decreased in amplitude and increased in latency as stimulus rate was increased from standard 7.1 clicks/s up to 507.81 clicks/s, with sharp reduction in AP amplitude at 97.66 clicks/s and reaching asymptote at 292.97 clicks/s. The summating potential (SP) of the ECochG, however, stayed relatively stable, resulting in increased SP/AP ratios with increasing rate. The SP/AP amplitude ratio showed more stability than AP amplitude findings, thus it is recommended for use in evaluation of cochlear and neural response. CONCLUSIONS: Results of both amplitude and latency data from this normative neural adaptation function of the auditory pathway serves as guide for improving diagnostic utility of both ECochG and ABR using CLAD as a reliable technique in distinguishing inner ear and auditory nerve disorders.

Newborn Auditory Brainstem Responses in Children with Developmental Disabilities.

We integrated data from a newborn hearing screening database and a preschool disability database to examine the relationship between newborn click evoked auditory brainstem responses (ABRs) and developmental disabilities. This sample included children with developmental delay (n = 2992), speech impairment (SI, n = 905), language impairment (n = 566), autism spectrum disorder (ASD, n = 370), and comparison children (n = 128,181). We compared the phase of the ABR waveform, a measure of sound processing latency, across groups. Children with SI and children with ASD had greater newborn ABR phase values than both the comparison group and the developmental delay group. Newborns later diagnosed with SI or ASD have slower neurological responses to auditory stimuli, suggesting sensory differences at birth.

Sensing echoes: temporal misalignment in auditory brainstem responses as the earliest marker of neurodevelopmental derailment.

Neurodevelopmental disorders are on the rise worldwide, with diagnoses that detect derailment from typical milestones by 3 to 4.5 years of age. By then, the circuitry in the brain has already reached some level of maturation that inevitably takes neurodevelopment through a different course. There is a critical need then to develop analytical methods that detect problems much earlier and identify targets for treatment. We integrate data from multiple sources, including neonatal auditory brainstem responses (ABR), clinical criteria detecting autism years later in those neonates, and similar ABR information for young infants and children who also received a diagnosis of autism spectrum disorders, to produce the earliest known digital screening biomarker to flag neurodevelopmental derailment in neonates. This work also defines concrete targets for treatment and offers a new statistical approach to aid in guiding a personalized course of maturation in line with the highly nonlinear, accelerated neurodevelopmental rates of change in early infancy.

Steady-state analysis of auditory evoked potentials over a wide range of stimulus repetition rates in awake vs. natural sleep.

OBJECTIVE: Auditory steady-state responses (ASSR) evoked by recurrent tones were assessed over a wide range of stimulus repetition rates embracing well the traditionally measured transient AEPs. Repetition rates of ≤ 10 Hz have received little attention in the context of the ASSR stimulus-response analysis approach which is speculated to provide technical advantages, if not additional/supplemental information, over more traditional transient stimulus-response paradigms. DESIGN: Magnitudes were measured at repetition rates from 0.75 to 80 Hz, using trains of recurrent tone-burst stimuli. STUDY SAMPLE: Twenty-five normal-hearing adults during sleep and awake. RESULTS: Results show that response magnitudes for adults tested during sleep were significantly larger than those for adults while awake at repetition rates <5 Hz. Magnitudes were largest at the two lowest repetition rates, as expected from corresponding results obtained using conventional methods. CONCLUSIONS: The analysis methods used in this paper may give information that will have applications for clinical testing. Results confirm and extend knowledge of the effects of repetition rate on AEPs over a range embracing the gamut of responses as traditionally classified, specifically at the beginning stages of natural sleep.

Steady-state analysis of auditory evoked potentials over a wide range of stimulus repetition rates: profile in children vs. adults.

OBJECTIVE: Auditory steady-state responses (ASSR) evoked by recurrent brief tones were assessed over a wide range of stimulus repetition rates apropos the traditionally measured obligatory, transient, auditory evoked potentials. Repetition rates of ≤ 10 Hz have received little attention in the context of the ASSR stimulus-response analysis approach, speculated to provide technical advantages/additional information over more traditional transient stimulus-response paradigms. DESIGN: Magnitudes were measured at repetition rates from 0.75 to 80 Hz, using trains of repeated tone-burst stimuli. STUDY SAMPLE: Twelve normal-hearing children and a reference sample of 25 young adults. RESULTS: Results show that response magnitudes were significantly larger in children than adults at repetition rates of ≤ 5 Hz. Magnitudes were largest at the two lowest repetition rates, following the trends expected from the transient auditory evoked potential (AEP) literature. The harmonic sum is proposed as a more appropriate measure of response magnitude than amplitude of the fundamental alone. CONCLUSIONS: The analysis methods used in this paper may give information that will have applications for clinical testing. Of pragmatic importance is that the stimulus rate profile could be determined without subjective wave identification and/or interpretation, and thus by a method that is inherently more objective than conventional AEP analysis.

The Effects of Middle-ear Stiffness on the Auditory Brainstem Neural Encoding of Phase.

The middle-ear system relies on a balance of mass and stiffness characteristics for transmitting sound from the external environment to the cochlea and auditory neural pathway. Phase is one aspect of sound that, when transmitted and encoded by both ears, contributes to binaural cue sensitivity and spatial hearing. The study aims were (i) to investigate the effects of middle-ear stiffness on the auditory brainstem neural encoding of phase in human adults with normal pure-tone thresholds and (ii) to investigate the relationships between middle-ear stiffness-induced changes in wideband acoustic immittance and neural encoding of phase. The auditory brainstem neural encoding of phase was measured using the auditory steady-state response (ASSR) with and without middle-ear stiffness elicited via contralateral activation of the middle-ear muscle reflex (MEMR). Middle-ear stiffness was quantified using a wideband acoustic immittance assay of acoustic absorbance. Statistical analyses demonstrated decreased ASSR phase lag and decreased acoustic absorbance with contralateral activation of the MEMR, consistent with increased middle-ear stiffness changing the auditory brainstem neural encoding of phase. There were no statistically significant correlations between stiffness-induced changes in wideband acoustic absorbance and ASSR phase. The findings of this study may have important implications for understanding binaural cue sensitivity and horizontal plane sound localization in audiologic and otologic clinical populations that demonstrate changes in middle-ear stiffness, including cochlear implant recipients who use combined electric and binaural acoustic hearing and otosclerosis patients.

Steady-state analysis of auditory evoked potentials over a wide range of stimulus repetition rates: profile in adults.

OBJECTIVE: Quasi-steady-state responses were assessed over a wide range of stimulus repetition rates embracing well the traditionally measured transient AEPs (obligatory auditory evoked potentials of all latencies). Repetition rates of ≤10 Hz have received little attention in the context of the ASSR stimulus-response analysis approach which is speculated to provide technical advantages, if not additional information, over more traditional transient stimulus-response paradigms. DESIGN: A measure introduced and defined as the sum of the response at the stimulus frequency and its harmonics. The magnitude of steady-state responses were measured at repetition rates from 0.75 to 80 Hz, using trains of repeated tone-burst stimuli. STUDY SAMPLE: Twenty-five normal-hearing adults. RESULTS: Results show that the magnitudes of the response across repetition rates are largest at the two lowest rates, following trends expected from the transient AEP literature. Good reliability overall was observed for the harmonic sum. CONCLUSIONS: The analysis methods used in this paper may give information that will have application for clinical testing. Of pragmatic importance is that the rate profile could be determined without subjective wave identification and/or interpretation, and thus by a method that is inherently more objective than conventional AEP tests.

Prolonged Auditory Brainstem Response in Universal Hearing Screening of Newborns with Autism Spectrum Disorder.

Previous studies report prolonged auditory brainstem response (ABR) in children and adults with autism spectrum disorder (ASD). Despite its promise as a biomarker, it is unclear whether healthy newborns who later develop ASD also show ABR abnormalities. In the current study, we extracted ABR data on 139,154 newborns from their Universal Newborn Hearing Screening, including 321 newborns who were later diagnosed with ASD. We found that the ASD newborns had significant prolongations of their ABR phase and V-negative latency compared with the non-ASD newborns. Newborns in the ASD group also exhibited greater variance in their latencies compared to previous studies in older ASD samples, likely due in part to the low intensity of the ABR stimulus. These findings suggest that newborns display neurophysiological variation associated with ASD at birth. Future studies with higher-intensity stimulus ABRs may allow more accurate predictions of ASD risk, which could augment the universal ABR test that currently screens millions of newborns worldwide. LAY SUMMARY: Children with autism spectrum disorder (ASD) have slow brain responses to sounds. We examined these brain responses from newborns' hearing tests and found that newborns who were later diagnosed with autism also had slower brain responses to sounds. Future studies might use these findings to better predict autism risk, with a hearing test that is already used on millions of newborns worldwide.

Intraoperative monitoring of hearing during cerebellopontine angle tumor surgery using transtympanic electrocochleography.

OBJECTIVE: To investigate the use of transtympanic electrocochleography (TT-ECochG) analyzed on-line by a detector strategy software that made possible automatic extraction of TT-ECochG components intraoperatively in real-time domain. PATIENTS: Fifteen patients with cerebellopontine angle tumor among 50 patients were included in this study. INTERVENTION: All subjects were operated on via middle fossa or retrosigmoid approach. Pure-tone average (PTA) was measured at 0.5, 1.0, and 2.0 kHz, and calculations were performed before and after surgery. Auditory function was monitored intraoperatively via TT-ECochG, and analyzed data were displayed on-line. MAIN OUTCOME MEASURES: TT-ECochG changes in morphology were described. Postoperative PTA elevation level correlated with TT-ECochG morphology changes occurring intraoperatively. RESULTS: Analyzed on-line, TT-ECochG data were displayed as first negative peak of compound action potential amplitude and latency in time domain every 3 to 5 seconds. A good correlation between postoperative PTA elevation and TT-ECochG morphology changes was showed (Spearman rank test, R = +0.93; t(N-2) = 9.00; p < 0.0001). CONCLUSION: TT-EcochG seemed to effectively mirror even minimal changes in auditory function during intraoperative monitoring in real-time domain. Developed strategy of on-line analysis makes the intraoperative hearing status assessment faster and easier.

Human Summating Potential Using Continuous Loop Averaging Deconvolution: Response Amplitudes Vary with Tone Burst Repetition Rate and Duration.

Electrocochleography (ECochG) to high repetition rate tone bursts may have advantages over ECochG to clicks with standard slow rates. Tone burst stimuli presented at a high repetition rate may enhance summating potential (SP) measurements by reducing neural contributions resulting from neural adaptation to high stimulus repetition rates. To allow for the analysis of the complex ECochG responses to high rates, we deconvolved responses using the Continuous Loop Averaging Deconvolution (CLAD) technique. We examined the effect of high stimulus repetition rate and stimulus duration on SP amplitude measurements made with extratympanic ECochG to tone bursts in 20 adult females with normal hearing. We used 500 and 2,000 Hz tone bursts of various stimulus durations (12, 6, 3 ms) and repetition rates (five rates ranging from 7.1 to 234.38/s). A within-subject repeated measures (rate x duration) analysis of variance was conducted. We found that, for both 500 and 2,000 Hz stimuli, the mean deconvolved SP amplitudes were larger at faster repetition rates (58.59 and 97.66/s) compared to slower repetition rates (7.1 and 19.53/s), and larger at shorter stimulus duration compared longer stimulus duration. Our concluding hypothesis is that large SP amplitude to short duration stimuli may originate primarily from neural excitation, and large SP amplitudes to long duration, fast repetition rate stimuli may originate from hair cell responses. While the hair cell or neural origins of the SP to various stimulus parameters remains to be validated, our results nevertheless provide normative data as a step toward applying the CLAD technique to understanding diseased ears.

The Effect of Stimulus Intensity and Carrier Frequency on Auditory Middle- and Long-Latency Evoked Potentials Using a Steady-State-Response Approach.

PURPOSE: The purpose of this study was to measure magnitude changes of auditory steady-state responses (ASSRs) and respective transient middle- and long-latency responses as a function of stimulus intensity and carrier frequency. The literature lacks clear consensus, including relationship to loudness. METHOD: A cohort of 48 adults with normal hearing was examined from a companion study (Tlumak, Durrant, & Delgado, 2015) on effects of aging. ASSRs were elicited by repeated tone-burst stimuli presented at rates of 40 and 0.75 Hz at 3 frequencies and 5 levels of stimulus intensity. The design also permitted scrutiny of any gender bias to the results. RESULTS: Similar to derived transient response findings, ASSR magnitude (harmonic sum) systematically increased with intensity. Input-output function only at 0.75 Hz approximated a log-log linear function. However, slopes fell well below that of doubling of loudness per 10 dB SPL. Results failed to demonstrate significance as a function of carrier frequency and gender for both repetition rates. CONCLUSION: Effects of stimulus intensity, carrier frequency, and gender on ASSRs were similar to those of their transient counterparts. Findings remain disappointing for objective loudness estimation. Results suggest only a clear linkage to the long-latency response and the 0.75-Hz magnitude but require careful consideration of limitations/underlying mechanisms when measuring loudness-related effects.

Simultaneous measurement of electrocochleography and cochlear blood flow during cochlear hypoxia in rabbits.

In this study, a new monitoring system is developed to measure cochlear blood flow (CBF) and electrocochleography (ECochG) during transient ischemic episodes of the cochlea. A newly designed otic probe was used for the simultaneous recordings of laser-Doppler CBF and ECochG directly from the round window (RW). The probe enabled the recording of high amplitude compound action potentials (CAP) and cochlear microphonics (CM) with few averages. Experiments were conducted on rabbits to generate episodes of cochlear ischemia by using timed compressions of the internal auditory artery (IAA). The computer monitoring system extracted and measured CAP and CM components from ECochG in real-time. Results indicate that CM and CAP generally followed CBF during compressions and releases of IAA. Both CBF values and CAP amplitudes showed an overshoot following the reperfusion. CAP amplitude measures were found to be very sensitive to ischemia showing very rapid amplitude, latency and morphological changes. CM amplitude decreased more slowly than the CAP and CBF. Simultaneous recordings of CBF and ECochG using the otic probe provide a valuable neuromonitoring tool to investigate the dynamic behavior of the cochlea during ischemia.

Neuromonitoring of cochlea and auditory nerve with multiple extracted parameters during induced hypoxia and nerve manipulation.

A system capable of comprehensive and detailed monitoring of the cochlea and the auditory nerve during intraoperative surgery was developed. The cochlear blood flow (CBF) and the electrocochleogram (ECochGm) were recorded at the round window (RW) niche using a specially designed otic probe. The ECochGm was further processed to obtain cochlear microphonics (CM) and compound action potentials (CAP). The amplitude and phase of the CM were used to quantify the activity of outer hair cells (OHC); CAP amplitude and latency were used to describe the auditory nerve and the synaptic activity of the inner hair cells (IHC). In addition, concurrent monitoring with a second electrophysiological channel was achieved by recording compound nerve action potential (CNAP) obtained directly from the auditory nerve. Stimulation paradigms, instrumentation and signal processing methods were developed to extract and differentiate the activity of the OHC and the IHC in response to three different frequencies. Narrow band acoustical stimuli elicited CM signals indicating mainly nonlinear operation of the mechano-electrical transduction of the OHCs. Special envelope detectors were developed and applied to the ECochGm to extract the CM fundamental component and its harmonics in real time. The system was extensively validated in experimental animal surgeries by performing nerve compressions and manipulations.

The Effect of Advancing Age on Auditory Middle- and Long-Latency Evoked Potentials Using a Steady-State-Response Approach.

PURPOSE: The purpose of the study was to objectively detect age-specific changes that occur in equivalent auditory steady-state responses (ASSRs), corresponding to transient middle- and long-latency auditory evoked potentials as a function of repetition rate and advancing age. METHOD: The study included 48 healthy hearing adults who were equally divided into 3 groups by age: 20-39, 40-59, and 60-79 years. ASSRs were recorded at 7 repetition rates from 40 down to 0.75 Hz, elicited by trains of repeated tone burst stimuli. RESULTS: Temporal analysis of middle- and long-latency equivalent ASSRs revealed no appreciable changes in the magnitudes of the response across the age groups. Likewise, the spectral analysis revealed that advancing age did not substantially affect the spectral content of the response at each repetition rate. Furthermore, the harmonic sum was not significantly different across the 3 age groups, between the younger adults versus the combined Older Group Sample 1 and Sample 2, and between the two extreme age groups (i.e., 20-39 vs. 60-79) for the middle- and long-latency equivalent ASSRs. CONCLUSION: Advancing age has no effect on the long-latency equivalent ASSRs; however, aging does affect the middle-latency equivalent ASSRs when the mean age difference is ≥ 40 years.

Evaluation of hearing and auditory nerve function by combining ABR, DPOAE and eABR tests into a single recording session.

In this article, we describe an efficient method for testing both auditory receptor and auditory nerve function in a single recording session. Auditory receptor function is tested in response to pure tone, tone burst and click acoustic stimuli (i.e. distortion products of otoacoustic emissions, DPOAE; and auditory-evoked brainstem responses, ABR). The function of the auditory neurons and nerve is measured in response to direct electric current stimulation (i.e. electrically evoked auditory brainstem responses, eABR). All measurements were obtained from anesthetized laboratory rats during single recording sessions using hardware and software stimulation and analysis programs developed by Intelligent Hearing Systems, Miami, FL.

Clinical use of skull tap vestibular evoked myogenic potentials for the diagnoses of the cerebellopontine angle tumor patients.

OBJECTIVE: To document our experiences using a new skull tapping induced Vestibular Evoked Myogenic Potentials (tap VEMPs) technique combined with standard Auditory Vestibular Evoked Myogenic Potentials (AC VEMPs) for advanced clinical assessment of cerebellopontine angle tumor (CPAT) patients. DESIGN AND STUDY SAMPLE: Three patients were selected in order to highlight observations shown in a larger patient population and to show the variability of the findings. Both tap VEMPs and AC VEMPs were acquired from the sternocleidomastoid muscle (SCM) with EMG-based biofeedback and monitoring. RESULTS: The usefulness of VEMPs was demonstrated, indicating the presence of a tumor and contributing additional information as to the involved nerve bundles in two out of the three cases. CONCLUSION: Due to the sensory organ dependency and related innervations differences, acquiring both AC VEMPs and tap VEMPs is likely to increase the probability of diagnosing CPATs and provide more information on the involved vestibular nerve bundles. This study demonstrates the feasibility of the possible expansion and combination of tap VEMPs and AC VEMPs techniques into a clinical diagnostic battery for advanced assessment of CPAT patients and its contribution as a guideline for the use of tap VEMPs in general.

Design of a clinically viable pneumatic system for the acquisition of pressure compensated otoacoustic emissions.

Otoacoustic emission (OAE) screening is perhaps one of the most common diagnostic tools used on both adults and children alike to clinically asses hearing health. However small to moderate middle ear pressures (both positive and negative), which are quite prevalent among the general population, are known to significantly reduce the OAE response specifically among frequencies below 2 kHz. This study focuses on the design and development of a software controlled syringe pump which will be used for the automatic compensation of middle ear pressure. This study reports validating test results which confirm the feasibility of using this system for future clinical trials.