Association between vitamin D deficiency and benign paroxysmal positional vertigo (BPPV) incidence and recurrence: a systematic review and meta-analysis.

OBJECTIVES: The objective of this study is to determine the relationship between serum vitamin D level and the risk of developing benign paroxysmal positional vertigo (BPPV) incidence and recurrence in countries in the Northern Hemisphere. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Scopus and Web of Science databases were searched for studies published between January 2000 and February 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Participants located in the Northern Hemisphere aged 18 or over with at least one episode of BPPV, serum 25-hydroxyvitamin D levels measured and reported, no comorbidities or history of vitamin D supplementation. DATA EXTRACTION AND SYNTHESIS: Data extraction and synthesis were performed by a single reviewer and checked by a second reviewer. Inclusion and exclusion criteria and risk of bias were assessed by two independent reviewers using the Newcastle Ottawa Tool for Cohort studies and Risk of Bias Assessment Tool for Nonrandomised Studies checklist for case-control studies. Meta-analysis was conducted using random effects models. Standard mean difference with a 95% CI was used to measure the relationship between vitamin D level and BPPV. RESULTS: The 35 articles identified by the literature search reported data of 9843 individuals. 19 studies (7387 individuals) were included in the BPPV incidence meta-analysis while 7 studies (622 individuals) were included in the BPPV recurrence meta-analysis. Lower serum vitamin D levels were found in BPPV incidence compared with controls, but the relationship between vitamin D levels in recurrent BPPV compared with non-recurrent disease remained uncertain. CONCLUSION: Results of this systematic review and meta-analysis demonstrated a negative correlation between serum vitamin D and BPPV incidence, while any relationship between serum vitamin D and BPPV recurrence remained uncertain. Risk of bias analysis revealed evidence of variable quality. There were insufficient data available to evaluate seasonal relationships between serum vitamin D and BPPV. Given the potential for this as a confounding factor, future research should aim to investigate this further. PROSPERO REGISTRATION NUMBER: CRD42021271840.

The ongoing search for cochlear synaptopathy in humans: Masked thresholds for brief tones in Threshold Equalizing Noise.

This study aimed to advance towards a clinical diagnostic method for detection of cochlear synaptopathy with the hypothesis that synaptopathy should be manifested in elevated masked thresholds for brief tones. This hypothesis was tested in tinnitus sufferers, as they are thought to have some degree of synaptopathy. Near-normal-hearing tinnitus sufferers and their matched controls were asked to detect pure tones with durations of 5, 10, 100, and 200 ms presented in low- and high-level Threshold Equalizing Noise. In addition, lifetime noise exposure was estimated for all participants. Contrary to the hypothesis, there was no significant difference in masked thresholds for brief tones between tinnitus sufferers and their matched controls. Masked thresholds were also not related to lifetime noise exposure. There are two possible explanations of the results: 1) the participants in our study did not have cochlear synaptopathy, or 2) synaptopathy does not lead to elevated masked thresholds for brief tones. This study adds a new approach to the growing list of behavioral methods that attempted to detect potential signs of cochlear synaptopathy in humans.

No Effect of Interstimulus Interval on Acoustic Reflex Thresholds.

The acoustic reflex (AR), a longstanding component of the audiological test battery, has received renewed attention in the context of noise-induced cochlear synaptopathy-the destruction of synapses between inner hair cells and auditory nerve fibers. Noninvasive proxy measures of synaptopathy are widely sought, and AR thresholds (ARTs) correlate closely with synaptic survival in rodents. However, measurement in humans at high stimulus frequencies-likely important when testing for noise-induced pathology-can be challenging; reflexes at 4 kHz are frequently absent or occur only at high stimulus levels, even in young people with clinically normal audiograms. This phenomenon may partly reflect differences across stimulus frequency in the temporal characteristics of the response; later onset of the response, earlier onset of adaptation, and higher rate of adaptation have been observed at 4 kHz than at 1 kHz. One temporal aspect of the response that has received little attention is the interstimulus interval (ISI); inadequate duration of ISI might lead to incomplete recovery of the response between successive presentations and consequent response fatigue. This research aimed to test for effects of ISI on ARTs in normally hearing young humans, measured at 1 and 4 kHz. Contrary to our hypotheses, increasing ISIs from 2.5 to 8.5 s did not reduce ART level, nor raise ART reliability. Results confirm that clinically measured ARTs-including those at 4 kHz-can exhibit excellent reliability and that relatively short (2.5 s) ISIs are adequate for the measurement of sensitive and reliable ARTs.

Effects of Age and Noise Exposure on Proxy Measures of Cochlear Synaptopathy.

Although there is strong histological evidence for age-related synaptopathy in humans, evidence for the existence of noise-induced cochlear synaptopathy in humans is inconclusive. Here, we sought to evaluate the relative contributions of age and noise exposure to cochlear synaptopathy using a series of electrophysiological and behavioral measures. We extended an existing cohort by including 33 adults in the age range 37 to 60, resulting in a total of 156 participants, with the additional older participants resulting in a weakening of the correlation between lifetime noise exposure and age. We used six independent regression models (corrected for multiple comparisons), in which age, lifetime noise exposure, and high-frequency audiometric thresholds were used to predict measures of synaptopathy, with a focus on differential measures. The models for auditory brainstem responses, envelope-following responses, interaural phase discrimination, and the co-ordinate response measure of speech perception were not statistically significant. However, both age and noise exposure were significant predictors of performance on the digit triplet test of speech perception in noise, with greater noise exposure (unexpectedly) predicting better performance in the 80 dB sound pressure level (SPL) condition and greater age predicting better performance in the 40 dB SPL condition. Amplitude modulation detection thresholds were also significantly predicted by age, with older listeners performing better than younger listeners at 80 dB SPL. Overall, the results are inconsistent with the predicted effects of synaptopathy.

Supra-threshold auditory brainstem response amplitudes in humans: Test-retest reliability, electrode montage and noise exposure.

The auditory brainstem response (ABR) is a sub-cortical evoked potential in which a series of well-defined waves occur in the first 10 ms after the onset of an auditory stimulus. Wave V of the ABR, particularly wave V latency, has been shown to be remarkably stable over time in individual listeners. However, little attention has been paid to the reliability of wave I, which reflects auditory nerve activity. This ABR component has attracted interest recently, as wave I amplitude has been identified as a possible non-invasive measure of noise-induced cochlear synaptopathy. The current study aimed to determine whether ABR wave I amplitude has sufficient test-retest reliability to detect impaired auditory nerve function in an otherwise normal-hearing listener. Thirty normal-hearing females were tested, divided equally into low- and high-noise exposure groups. The stimulus was an 80 dB nHL click. ABR recordings were made from the ipsilateral mastoid and from the ear canal (using a tiptrode). Although there was some variability between listeners, wave I amplitude had high test-retest reliability, with an intraclass correlation coefficient (ICC) comparable to that for wave V amplitude. There were slight gains in reliability for wave I amplitude when recording from the ear canal (ICC of 0.88) compared to the mastoid (ICC of 0.85). The summating potential (SP) and ratio of SP to wave I were also quantified and found to be much less reliable than measures of wave I and V amplitude. Finally, we found no significant differences in the amplitude of any wave components between low- and high-noise exposure groups. We conclude that, if the other sources of between-subject variability can be controlled, wave I amplitude is sufficiently reliable to accurately characterize individual differences in auditory nerve function.

Effects of noise exposure on young adults with normal audiograms II: Behavioral measures.

An estimate of lifetime noise exposure was used as the primary predictor of performance on a range of behavioral tasks: frequency and intensity difference limens, amplitude modulation detection, interaural phase discrimination, the digit triplet speech test, the co-ordinate response speech measure, an auditory localization task, a musical consonance task and a subjective report of hearing ability. One hundred and thirty-eight participants (81 females) aged 18-36 years were tested, with a wide range of self-reported noise exposure. All had normal pure-tone audiograms up to 8 kHz. It was predicted that increased lifetime noise exposure, which we assume to be concordant with noise-induced cochlear synaptopathy, would elevate behavioral thresholds, in particular for stimuli with high levels in a high spectral region. However, the results showed little effect of noise exposure on performance. There were a number of weak relations with noise exposure across the test battery, although many of these were in the opposite direction to the predictions, and none were statistically significant after correction for multiple comparisons. There were also no strong correlations between electrophysiological measures of synaptopathy published previously and the behavioral measures reported here. Consistent with our previous electrophysiological results, the present results provide no evidence that noise exposure is related to significant perceptual deficits in young listeners with normal audiometric hearing. It is possible that the effects of noise-induced cochlear synaptopathy are only measurable in humans with extreme noise exposures, and that these effects always co-occur with a loss of audiometric sensitivity.

Effects of noise exposure on young adults with normal audiograms I: Electrophysiology.

Noise-induced cochlear synaptopathy has been demonstrated in numerous rodent studies. In these animal models, the disorder is characterized by a reduction in amplitude of wave I of the auditory brainstem response (ABR) to high-level stimuli, whereas the response at threshold is unaffected. The aim of the present study was to determine if this disorder is prevalent in young adult humans with normal audiometric hearing. One hundred and twenty six participants (75 females) aged 18-36 were tested. Participants had a wide range of lifetime noise exposures as estimated by a structured interview. Audiometric thresholds did not differ across noise exposures up to 8 kHz, although 16-kHz audiometric thresholds were elevated with increasing noise exposure for females but not for males. ABRs were measured in response to high-pass (1.5 kHz) filtered clicks of 80 and 100 dB peSPL. Frequency-following responses (FFRs) were measured to 80 dB SPL pure tones from 240 to 285 Hz, and to 80 dB SPL 4 kHz pure tones amplitude modulated at frequencies from 240 to 285 Hz (transposed tones). The bandwidth of the ABR stimuli and the carrier frequency of the transposed tones were chosen to target the 3-6 kHz characteristic frequency region which is usually associated with noise damage in humans. The results indicate no relation between noise exposure and the amplitude of the ABR. In particular, wave I of the ABR did not decrease with increasing noise exposure as predicted. ABR wave V latency increased with increasing noise exposure for the 80 dB peSPL click. High carrier-frequency (envelope) FFR signal-to-noise ratios decreased as a function of noise exposure in males but not females. However, these correlations were not significant after the effects of age were controlled. The results suggest either that noise-induced cochlear synaptopathy is not a significant problem in young, audiometrically normal adults, or that the ABR and FFR are relatively insensitive to this disorder in young humans, although it is possible that the effects become more pronounced with age.

The perception of complex pitch in cochlear implants: A comparison of monopolar and tripolar stimulation.

Cochlear implant listeners typically perform poorly in tasks of complex pitch perception (e.g., musical pitch and voice pitch). One explanation is that wide current spread during implant activation creates channel interactions that may interfere with perception of temporal fundamental frequency information contained in the amplitude modulations within channels. Current focusing using a tripolar mode of stimulation has been proposed as a way of reducing channel interactions, minimising spread of excitation and potentially improving place and temporal pitch cues. The present study evaluated the effect of mode in a group of cochlear implant listeners on a pitch ranking task using male and female singing voices separated by either a half or a quarter octave. Results were variable across participants, but on average, pitch ranking was at chance level when the pitches were a quarter octave apart and improved when the difference was a half octave. No advantage was observed for tripolar over monopolar mode at either pitch interval, suggesting that previously published psychophysical advantages for focused modes may not translate into improvements in complex pitch ranking. Evaluation of the spectral centroid of the stimulation pattern, plus a lack of significant difference between male and female voices, suggested that participants may have had difficulty in accessing temporal pitch cues in either mode.

Vestibular receptors contribute to cortical auditory evoked potentials.

Acoustic sensitivity of the vestibular apparatus is well-established, but the contribution of vestibular receptors to the late auditory evoked potentials of cortical origin is unknown. Evoked potentials from 500 Hz tone pips were recorded using 70 channel EEG at several intensities below and above the vestibular acoustic threshold, as determined by vestibular evoked myogenic potentials (VEMPs). In healthy subjects both auditory mid- and long-latency auditory evoked potentials (AEPs), consisting of Na, Pa, N1 and P2 waves, were observed in the sub-threshold conditions. However, in passing through the vestibular threshold, systematic changes were observed in the morphology of the potentials and in the intensity dependence of their amplitude and latency. These changes were absent in a patient without functioning vestibular receptors. In particular, for the healthy subjects there was a fronto-central negativity, which appeared at about 42 ms, referred to as an N42, prior to the AEP N1. Source analysis of both the N42 and N1 indicated involvement of cingulate cortex, as well as bilateral superior temporal cortex. Our findings are best explained by vestibular receptors contributing to what were hitherto considered as purely auditory evoked potentials and in addition tentatively identify a new component that appears to be primarily of vestibular origin.

Place specificity of monopolar and tripolar stimuli in cochlear implants: the influence of residual masking.

This experiment investigated whether place specificity of neural activity evoked by cochlear implant stimulation is improved in tripolar compared to monopolar mode using a forward masking protocol addressing some limitations of previous methods of measurement and analysis. The amount of residual masking (masking remaining at long masker-probe delays) was also measured, and its potential influence on the specificity measures was evaluated. The masker stimulus comprised equally loud interleaved mono- or tripolar stimulation on two electrodes equidistant from a central probe electrode in an apical and basal direction, reducing the influence of off-site listening. The effect of masker-probe distance on the threshold shift of the tripolar probe was analyzed to derive a measure of place specificity. On average, tripolar maskers were more place specific than monopolar maskers, although the mean effect was small. There was no significant effect of masker level on specificity or on the differences observed between modes. The mean influence of residual masking on normalized masking functions was similar for the two modes and, therefore, did not influence the comparison of specificity between the modes. However, variability in amount of residual masking was observed between subjects, and therefore should be considered in forward masking studies that compare place specificity across subjects.

Voice gender differences and separation of simultaneous talkers in cochlear implant users with residual hearing.

Perception of a target voice in the presence of a competing talker, of same or different gender as the target, was investigated in cochlear implant users, in implant-alone and bimodal (acoustic hearing in the non-implanted ear) conditions. Recordings of two male and two female talkers acted as targets and maskers, to investigate whether bimodal benefit increased for different compared to same gender target/maskers due to increased ability to perceive and utilize fundamental frequency and spectral-shape differences. In both listening conditions participants showed benefit of target/masker gender difference. There was an overall bimodal benefit, which was independent of target/masker gender difference.

Using the auditory steady state response to record response amplitude curves. A possible fast objective method for diagnosing dead regions.

OBJECTIVES: To assess a novel objective method of measuring response amplitude curves (RACs) using auditory steady state responses in adults. DESIGN: RACs were recorded in 20 normal-hearing adults. The RACs were measured by recording the changes in the amplitude of the auditory steady state response in the presence of (1) swept frequency narrowband masking noise and (2) fixed narrowband masking noise. RESULTS: The mean recorded RAC tip frequency for a 2-kHz signal was 2250 Hz for the swept masker method and 2239 Hz for the fixed masker method. The estimated repeatability coefficients, calculated using an assumed mean difference of zero, were 389 Hz for the swept method and 342 Hz for the fixed method. CONCLUSIONS: These initial results indicate that the swept- and fixed-masking methods appear to be viable and fast ways to record RACs in normal-hearing adults. Further work is needed to further optimize the accuracy of the tip frequency estimation and to establish the normative range of tip frequencies over a wide range of test frequencies in normal-hearing and hearing-impaired subjects.

Dead regions in the cochlea and enhancement of frequency discrimination: Effects of audiogram slope, unilateral versus bilateral loss, and hearing-aid use.

Following a restricted lesion of the cochlea, which produces a "dead region" (DR), animal experiments have revealed an increase in the cortical representation of frequencies just below the edge frequency (f(e)) of the DR. This may result in improved difference limens for frequency (DLFs) just below f(e). In previous studies to assess this, the value of f(e) was not determined precisely. We measured DLFs using human subjects with DRs for whom the values of f(e) had been determined precisely using psychophysical tuning curves. To prevent use of loudness cues, stimuli for the measurement of DLFs had a mean level falling along an equal-loudness contour and levels were roved over a 12-dB range. DLFs were measured for thirteen subjects with a DR in at least one ear. Almost all subjects with bilateral hearing loss exhibited enhanced DLFs near f(e), consistent with cortical reorganisation. This occurred for subjects whose audiograms had both steep and shallow slopes, regardless of hearing aid use, and for two subjects with low-frequency DRs. One subject with a high-frequency DR in one ear and good hearing in the other ear showed an enhanced DLF in her better ear.

Development of a fast method for determining psychophysical tuning curves.

Psychophysical tuning curves (PTCs) can be used to assess the frequency selectivity of the auditory system and to detect and delimit "dead regions" in the cochlea. However, the traditional method for determining PTCs takes too long for use in clinical practice. We evaluated a fast method for determining PTCs, using a band of noise that sweeps in centre frequency and a Békésy method to adjust the masker level required for threshold. The shapes of the PTCs were similar for the fast and traditional methods, for both normally hearing and hearing-impaired subjects. Rates of change of masker level of 2 dB/s or less gave the most reliable results. A relatively wide bandwidth (20 percent of the signal frequency or 320 Hz, whichever is the smaller) was needed to minimise the influence of beat detection. When the signal frequency fell within a dead region, the fast method gave PTCs with shifted tips.

Factors affecting psychophysical tuning curves for hearing-impaired subjects with high-frequency dead regions.

A dead region (DR) is a region of the cochlea where there are no functioning inner hair cells and/or neurons. DRs can be detected using the threshold-equalizing-noise (TEN) test, but psychophysical tuning curves (PTCs) are sometimes used to give a more precise estimate of the edge frequency of a DR; a shifted tip of the PTC indicates a DR. We show here that the shapes of PTCs for hearing-impaired subjects can be influenced by the detection of beats and simple difference tones (SDTs). As a result, PTCs can have tips at f(s), even when f(s) falls in a DR. PTCs were measured for subjects with mild to moderate low-frequency and severe high-frequency hearing loss using sinusoidal and narrowband noise maskers (80-, 160-, 320-Hz wide): (1) in quiet; (2) in the presence of additional lowpass filtered noise (LF noise) designed to mask SDTs; (3) in the presence of a pair of low-frequency tones designed to interfere with the detection of beats (MDI tones). In condition (1), the PTCs were often W-shaped, with a sharp tip at f(s). This occurred less for the wider noise bandwidths. For subjects with good low-frequency hearing, the LF noise often reduced or eliminated the tip at f(s), suggesting that this tip was partly caused by detection of SDTs. For the sinusoidal and 80-Hz wide noise maskers, the addition of the MDI tones reduced the masker level required for threshold for masker frequencies adjacent to f(s), for nearly all subjects, suggesting a strong influence of beat detection. To minimize the influence of beats, we recommend using noise maskers with a bandwidth of 160 or (preferably) 320 Hz. In cases of near-normal hearing at low frequencies, we recommend using an additional LF noise to mask SDTs.

Factors affecting psychophysical tuning curves for normally hearing subjects.

These experiments were conducted to clarify the influence of beats and combination products on psychophysical tuning curves (PTCs) for normally hearing subjects. PTCs for 1- and 4-kHz sinusoidal signals were determined using as maskers a sinusoidal tone and 80-, 160-, and 320-Hz wide bands of noise. PTCs obtained using the sinusoidal masker showed distinct irregularities, particularly for masker frequencies close to the signal frequency. The PTCs determined for the noise maskers were more regular. The broader the masker, the more regular were the shapes of the PTCs. To reduce the detectability of beats produced by the interaction of the signal and masker, a pair of low-frequency tones, called "Modulation detection interference (MDI) tones", was used to introduce beats at the same rate. The MDI tones reduced the threshold level of the sinusoidal masker by up to 20 dB for frequencies within 300 Hz of the signal frequency; a similar but smaller effect was found when an 80-Hz wide masker was used. Adding a lowpass filtered (LF) noise to the sinusoidal or narrowband noise masker did not affect the low-frequency sides of the PTCs, suggesting no influence of combination products. The LF noise did affect the high-frequency sides of the PTCs, but this can be attributed to it reducing off-frequency listening. To achieve a PTC whose shape around the tip is minimally affected by beats, we propose using a noise masker with a bandwidth approximately equal to the bandwidth of the auditory filter for which the PTC is measured.