Changes in visually and auditory attended audiovisual speech processing in cochlear implant users: A longitudinal ERP study.

Limited auditory input, whether caused by hearing loss or by electrical stimulation through a cochlear implant (CI), can be compensated by the remaining senses. Specifically for CI users, previous studies reported not only improved visual skills, but also altered cortical processing of unisensory visual and auditory stimuli. However, in multisensory scenarios, it is still unclear how auditory deprivation (before implantation) and electrical hearing experience (after implantation) affect cortical audiovisual speech processing. Here, we present a prospective longitudinal electroencephalography (EEG) study which systematically examined the deprivation- and CI-induced alterations of cortical processing of audiovisual words by comparing event-related potentials (ERPs) in postlingually deafened CI users before and after implantation (five weeks and six months of CI use). A group of matched normal-hearing (NH) listeners served as controls. The participants performed a word-identification task with congruent and incongruent audiovisual words, focusing their attention on either the visual (lip movement) or the auditory speech signal. This allowed us to study the (top-down) attention effect on the (bottom-up) sensory cortical processing of audiovisual speech. When compared to the NH listeners, the CI candidates (before implantation) and the CI users (after implantation) exhibited enhanced lipreading abilities and an altered cortical response at the N1 latency range (90-150 ms) that was characterized by a decreased theta oscillation power (4-8 Hz) and a smaller amplitude in the auditory cortex. After implantation, however, the auditory-cortex response gradually increased and developed a stronger intra-modal connectivity. Nevertheless, task efficiency and activation in the visual cortex was significantly modulated in both groups by focusing attention on the visual as compared to the auditory speech signal, with the NH listeners additionally showing an attention-dependent decrease in beta oscillation power (13-30 Hz). In sum, these results suggest remarkable deprivation effects on audiovisual speech processing in the auditory cortex, which partially reverse after implantation. Although even experienced CI users still show distinct audiovisual speech processing compared to NH listeners, pronounced effects of (top-down) direction of attention on (bottom-up) audiovisual processing can be observed in both groups. However, NH listeners but not CI users appear to show enhanced allocation of cognitive resources in visually as compared to auditory attended audiovisual speech conditions, which supports our behavioural observations of poorer lipreading abilities and reduced visual influence on audition in NH listeners as compared to CI users.

[Vestibular Schwannoma: Factors in Therapy Decision-Making]. / Vestibularisschwannom: Faktoren bei der Therapieentscheidung.

The treatment of vestibular schwannomas (VS) has always posed a challenge for physicians. Three essential treatment principles are available: wait-and-scan, surgery, and stereotactic radiotherapy. In addition to the type of treatment, decisions must be made regarding the optimal timing of therapy, the combination of different treatment modalities, the potential surgical approach, and the type and intensity of radiation. Factors influencing the therapy decision include tumor location and size or stage, patient age, comorbidities, symptoms, postoperative hearing rehabilitation options, patient preferences, and, not least, the experience of the surgeons and the personnel and technical capabilities of the clinical site. This article begins with a brief overview of vestibular schwannomas, then outlines the fundamental interdisciplinary treatment options, and finally discusses the ENT (ear, nose, and throat)-relevant factors in the therapy decision.

Effects of noise and noise reduction on audiovisual speech perception in cochlear implant users: An ERP study.

OBJECTIVE: Hearing with a cochlear implant (CI) is difficult in noisy environments, but the use of noise reduction algorithms, specifically ForwardFocus, can improve speech intelligibility. The current event-related potentials (ERP) study examined the electrophysiological correlates of this perceptual improvement. METHODS: Ten bimodal CI users performed a syllable-identification task in auditory and audiovisual conditions, with syllables presented from the front and stationary noise presented from the sides. Brainstorm was used for spatio-temporal evaluation of ERPs. RESULTS: CI users revealed an audiovisual benefit as reflected by shorter response times and greater activation in temporal and occipital regions at P2 latency. However, in auditory and audiovisual conditions, background noise hampered speech processing, leading to longer response times and delayed auditory-cortex-activation at N1 latency. Nevertheless, activating ForwardFocus resulted in shorter response times, reduced listening effort and enhanced superior-frontal-cortex-activation at P2 latency, particularly in audiovisual conditions. CONCLUSIONS: ForwardFocus enhances speech intelligibility in audiovisual speech conditions by potentially allowing the reallocation of attentional resources to relevant auditory speech cues. SIGNIFICANCE: This study shows for CI users that background noise and ForwardFocus differentially affect spatio-temporal cortical response patterns, both in auditory and audiovisual speech conditions.

Electrophysiological differences and similarities in audiovisual speech processing in CI users with unilateral and bilateral hearing loss.

Hearing with a cochlear implant (CI) is limited compared to natural hearing. Although CI users may develop compensatory strategies, it is currently unknown whether these extend from auditory to visual functions, and whether compensatory strategies vary between different CI user groups. To better understand the experience-dependent contributions to multisensory plasticity in audiovisual speech perception, the current event-related potential (ERP) study presented syllables in auditory, visual, and audiovisual conditions to CI users with unilateral or bilateral hearing loss, as well as to normal-hearing (NH) controls. Behavioural results revealed shorter audiovisual response times compared to unisensory conditions for all groups. Multisensory integration was confirmed by electrical neuroimaging, including topographic and ERP source analysis, showing a visual modulation of the auditory-cortex response at N1 and P2 latency. However, CI users with bilateral hearing loss showed a distinct pattern of N1 topography, indicating a stronger visual impact on auditory speech processing compared to CI users with unilateral hearing loss and NH listeners. Furthermore, both CI user groups showed a delayed auditory-cortex activation and an additional recruitment of the visual cortex, and a better lip-reading ability compared to NH listeners. In sum, these results extend previous findings by showing distinct multisensory processes not only between NH listeners and CI users in general, but even between CI users with unilateral and bilateral hearing loss. However, the comparably enhanced lip-reading ability and visual-cortex activation in both CI user groups suggest that these visual improvements are evident regardless of the hearing status of the contralateral ear.

Revealing Perceptional and Cognitive Mechanisms in Static and Dynamic Cocktail Party Listening by Means of Error Analyses.

In cocktail party situations multiple talkers speak simultaneously, which causes listening to be perceptually and cognitively challenging. Such situations can either be static (fixed target talker) or dynamic, meaning the target talker switches occasionally and in a potentially unpredictable way. To shed light on the perceptional and cognitive mechanisms in static and dynamic cocktail party situations, we conducted an analysis of error types that occur during a multi-talker speech recognition test. The error analysis distinguished between misunderstood or omitted words (random errors) and target-masker confusions. To investigate the effects of aging and hearing impairment, we compared data from three listener groups, comprised of young as well as older adults with and without hearing loss. In the static condition, error rates were generally very low, except for the older hearing-impaired listeners. Consistent with the assumption of decreased audibility, they showed a notable amount of random errors. In the dynamic condition, errors increased compared to the static condition, especially immediately following a target talker switch. Those increases were similar for random and confusion errors. The older hearing-impaired listeners showed greater difficulties than the younger adults in trials not preceded by a switch. These results suggest that the load associated with dynamic cocktail party listening affects the ability to focus attention on the talker of interest and the retrieval of words from short-term memory, as indicated by the increased amount of confusion and random errors. This was most pronounced in the older hearing-impaired listeners proposing an interplay of perceptual and cognitive mechanisms.

Side-of-Implantation Effect on Functional Asymmetry in the Auditory Cortex of Single-Sided Deaf Cochlear-Implant Users.

Cochlear implants (CIs) allow to restore the hearing function in profoundly deaf individuals. Due to the degradation of the stimulus by CI signal processing, implanted individuals with single-sided deafness (SSD) have the specific challenge that the input highly differs between their ears. The present study compared normal-hearing (NH) listeners (N = 10) and left- and right-ear implanted SSD CI users (N = 10 left, N = 9 right), to evaluate cortical speech processing between CI- and NH-ears and to explore for side-of-implantation effects. The participants performed a two-deviant oddball task, separately with the left and the right ear. Auditory event-related potentials (ERPs) in response to syllables were compared between proficient and non-proficient CI users, as well as between CI and NH ears. The effect of the side of implantation was analysed on the sensor and the source level. CI proficiency could be distinguished based on the ERP amplitudes of the N1 and the P3b. Moreover, syllable processing via the CI ear, when compared to the NH ear, resulted in attenuated and delayed ERPs. In addition, the left-ear implanted SSD CI users revealed an enhanced functional asymmetry in the auditory cortex than right-ear implanted SSD CI users, regardless of whether the syllables were perceived via the CI or the NH ear. Our findings reveal that speech-discrimination proficiency in SSD CI users can be assessed by N1 and P3b ERPs. The results contribute to a better understanding of the rehabilitation success in SSD CI users by showing that cortical speech processing in SSD CI users is affected by CI-related stimulus degradation and experience-related functional changes in the auditory cortex.

The timecourse of multisensory speech processing in unilaterally stimulated cochlear implant users revealed by ERPs.

A cochlear implant (CI) is an auditory prosthesis which can partially restore the auditory function in patients with severe to profound hearing loss. However, this bionic device provides only limited auditory information, and CI patients may compensate for this limitation by means of a stronger interaction between the auditory and visual system. To better understand the electrophysiological correlates of audiovisual speech perception, the present study used electroencephalography (EEG) and a redundant target paradigm. Postlingually deafened CI users and normal-hearing (NH) listeners were compared in auditory, visual and audiovisual speech conditions. The behavioural results revealed multisensory integration for both groups, as indicated by shortened response times for the audiovisual as compared to the two unisensory conditions. The analysis of the N1 and P2 event-related potentials (ERPs), including topographic and source analyses, confirmed a multisensory effect for both groups and showed a cortical auditory response which was modulated by the simultaneous processing of the visual stimulus. Nevertheless, the CI users in particular revealed a distinct pattern of N1 topography, pointing to a strong visual impact on auditory speech processing. Apart from these condition effects, the results revealed ERP differences between CI users and NH listeners, not only in N1/P2 ERP topographies, but also in the cortical source configuration. When compared to the NH listeners, the CI users showed an additional activation in the visual cortex at N1 latency, which was positively correlated with CI experience, and a delayed auditory-cortex activation with a reversed, rightward functional lateralisation. In sum, our behavioural and ERP findings demonstrate a clear audiovisual benefit for both groups, and a CI-specific alteration in cortical activation at N1 latency when auditory and visual input is combined. These cortical alterations may reflect a compensatory strategy to overcome the limited CI input, which allows the CI users to improve the lip-reading skills and to approximate the behavioural performance of NH listeners in audiovisual speech conditions. Our results are clinically relevant, as they highlight the importance of assessing the CI outcome not only in auditory-only, but also in audiovisual speech conditions.

Age effects on cognitive functions and speech-in-noise processing: An event-related potential study with cochlear-implant users and normal-hearing listeners.

A cochlear implant (CI) can partially restore hearing in individuals with profound sensorineural hearing loss. However, electrical hearing with a CI is limited and highly variable. The current study aimed to better understand the different factors contributing to this variability by examining how age affects cognitive functions and cortical speech processing in CI users. Electroencephalography (EEG) was applied while two groups of CI users (young and elderly; N = 13 each) and normal-hearing (NH) listeners (young and elderly; N = 13 each) performed an auditory sentence categorization task, including semantically correct and incorrect sentences presented either with or without background noise. Event-related potentials (ERPs) representing earlier, sensory-driven processes (N1-P2 complex to sentence onset) and later, cognitive-linguistic integration processes (N400 to semantically correct/incorrect sentence-final words) were compared between the different groups and speech conditions. The results revealed reduced amplitudes and prolonged latencies of auditory ERPs in CI users compared to NH listeners, both at earlier (N1, P2) and later processing stages (N400 effect). In addition to this hearing-group effect, CI users and NH listeners showed a comparable background-noise effect, as indicated by reduced hit rates and reduced (P2) and delayed (N1/P2) ERPs in conditions with background noise. Moreover, we observed an age effect in CI users and NH listeners, with young individuals showing improved specific cognitive functions (working memory capacity, cognitive flexibility and verbal learning/retrieval), reduced latencies (N1/P2), decreased N1 amplitudes and an increased N400 effect when compared to the elderly. In sum, our findings extend previous research by showing that the CI users' speech processing is impaired not only at earlier (sensory) but also at later (semantic integration) processing stages, both in conditions with and without background noise. Using objective ERP measures, our study provides further evidence of strong age effects on cortical speech processing, which can be observed in both the NH listeners and the CI users. We conclude that elderly individuals require more effortful processing at sensory stages of speech processing, which however seems to be at the cost of the limited resources available for the later semantic integration processes.

Costs of dynamic cocktail party listening: Investigating the effects of cognitive abilities and hearing impairment.

Situations with multiple competing talkers are especially challenging for listeners with hearing impairment. These "cocktail party" situations can either be static (fixed target talker) or dynamic (changing target talker). Relative to static situations, dynamic listening is typically associated with increased cognitive load and decreased speech recognition ("costs"). This study addressed the role of hearing impairment and cognition in two groups of older listeners with and without hearing loss. In most of the dynamic situations, the costs did not differ between the listener groups. There was no clear evidence that overall costs show an association with the individuals' cognitive abilities.

Letter to the Editor Concerning Skuk et al., "Parameter-Specific Morphing Reveals Contributions of Timbre and Fundamental Frequency Cues to the Perception of Voice Gender and Age in Cochlear Implant Users".

Purpose The purpose of this letter is to compare results by Skuk et al. (2020) with Meister et al. (2016) and to point to a potential general influence of stimulus type. Conclusion Our conclusion is that presenting sentences may give cochlear implant recipients the opportunity to use timbre cues for voice perception. This might not be the case when presenting brief and sparse stimuli such as consonant-vowel-consonant or single words, which were applied in the majority of studies.

Static and dynamic cocktail party listening in younger and older adults.

Verbal communication often takes place in situations with several simultaneous speakers ("cocktail party listening"). These situations can be static (only one listening target) or dynamic (with alternating targets). In particular, dynamic cocktail party listening is believed to generate extra cognitive load and appears to be particularly demanding for older listeners. Two groups of younger and older listeners with good hearing and normal cognition participated in the present study. Three different, spatially separated talker voices uttering matrix sentences were presented to each listener with varying types and probabilities of target switches. Moreover, several neuropsychological tests were conducted to investigate general cognitive characteristics that may be important for speech understanding in these situations. In a static condition with a priori knowledge of the target talker, both age groups revealed very high speech recognition performance. In comparison, dynamic conditions caused extra costs associated with the need to monitor different potential sound sources and to refocus attention when the target changed. The amount of costs depended on the probability and type of target talker alterations. Again, no significant age-group differences were found. No significant associations of cognitive characteristics and costs could be shown. However, a more fine-grained analysis based on the calculation of general and specific switch costs showed different mechanisms in older and younger listeners. This study confirms that dynamic cocktail party listening is associated with costs that depend on the type and probability of target switches. It extends previous research by showing that the effects of switching type and probability are similar for younger and older listeners with good hearing and good cognitive abilities. It further shows that, despite comparable costs of dynamic listening, mechanisms are different for the two age groups, as switching auditory attention may be preserved with aging, but monitoring different sound sources appears to be more difficult for older adults.

Comparison of the Effects of Two Cochlear Implant Fine Structure Coding Strategies on Speech Perception.

Purpose This study aims to investigate the effect of upgrading from the fine structure processing (FSP) coding strategy to the novel fine structure strategy "FS4" in adults in adults with cochlear implants manufactured by MED-EL GmbH (Innsbruck, Austria). Method A crossover, double-blinded study was conducted for 12 weeks. Twelve adult participants were randomly assigned to two groups. During the first 6-week test interval, one group continued to use their everyday FSP strategy, whereas the other group was upgraded to the FS4 strategy. In the second 6-week interval, the two groups switched coding strategies. Speech perception was measured at the end of each test interval with the Oldenburg Sentence Test and the Göttingen Sentence Test. Participants completed the Speech, Spatial and Qualities of Hearing Scale at the end of each test interval and a simple preference test at the end of the study. Results There was no significant difference in speech perception test results obtained with the Oldenburg Sentence Test and the Göttingen Sentence Test, neither in quiet nor in noise. Participants' Speech, Spatial and Qualities of Hearing Scale self-evaluation and preference test results showed that the two coding strategies had similar effects on their hearing perception. No clear preference for either of the strategies was found. Conclusions Speech perception test results and the participants' level of satisfaction were similar for the two FS coding strategies. Despite differences in the presentation of temporal fine structure between FSP and FS4, a clear benefit of the newer FS4 strategy could not be shown.

Voice fundamental frequency differences and speech recognition with noise and speech maskers in cochlear implant recipients.

Cochlear implant (CI) recipients are limited in their perception of voice cues, such as the fundamental frequency (F0). This has important consequences for speech recognition when several talkers speak simultaneously. This examination considered the comparison of clear speech and noise-vocoded sentences as maskers. For the speech maskers it could be shown that good CI performers are able to benefit from F0 differences between target and masker. This was due to the fact that a F0 difference of 80 Hz significantly reduced target-masker confusions, an effect that was slightly more pronounced in bimodal than in bilateral users.

Low background noise increases cognitive load in older adults listening to competing speech.

This letter describes a dual-task paradigm sensitive to noise masking at favorable signal-to-noise ratios (SNRs). Two competing sentences differing in voice and context cues were presented against noise at SNRs of +2 and +6 dB. Listeners were asked to repeat back words from both competing sentences while prioritizing one of them. Recognition of the high-priority sentences was high and did not depend on the SNR. In contrast, recognition of the low-priority sentences was low and showed a significant SNR effect that was related to the listener's working memory capacity. This suggests that even subtle noise masking causes cognitive load in competing-talker situations.

Examination of Prosody and Timbre Perception in Adults With Cochlear Implants Comparing Different Fine Structure Coding Strategies.

PURPOSE: This study aimed to investigate whether adults with cochlear implants benefit from a change of fine structure (FS) coding strategies regarding the discrimination of prosodic speech cues, timbre cues, and the identification of natural instruments. The FS processing (FSP) coding strategy was compared to 2 settings of the FS4 strategy. METHOD: A longitudinal crossover, double-blinded study was conducted. This study consisted of 2 parts, with 14 participants in the first part and 12 participants in the second part. Each part lasted 3 months, in which participants were alternately fitted with either the established FSP strategy or 1 of the 2 newly developed FS4 settings. Participants had to complete an intonation identification test; a timbre discrimination test in which 1 of 2 isolated cues changed, either the spectral centroid or the spectral irregularity; and an instrument identification test. RESULTS: A significant effect was seen in the discrimination of spectral irregularity with 1 of the 2 FS4 settings. The improvement was seen in the FS4 setting in which the upper envelope channels had a low stimulation rate. This improvement was not seen with the FS4 setting that had a higher stimulation rate on the envelope channels. CONCLUSIONS: In general, the FSP strategy and the 2 settings of the FS4 strategy provided similar levels in the perception of prosody and timbre cues, as well as in the identification of instruments.

Assessment of hearing aid algorithms using a master hearing aid: the influence of hearing aid experience on the relationship between speech recognition and cognitive capacity.

OBJECTIVES: Model-based hearing aid development considers the assessment of speech recognition using a master hearing aid (MHA). It is known that aided speech recognition in noise is related to cognitive factors such as working memory capacity (WMC). This relationship might be mediated by hearing aid experience (HAE). The aim of this study was to examine the relationship of WMC and speech recognition with a MHA for listeners with different HAE. DESIGN: Using the MHA, unaided and aided 80% speech recognition thresholds in noise were determined. Individual WMC capacity was assed using the Verbal Learning and Memory Test (VLMT) and the Reading Span Test (RST). STUDY SAMPLE: Forty-nine hearing aid users with mild to moderate sensorineural hearing loss divided into three groups differing in HAE. RESULTS: Whereas unaided speech recognition did not show a significant relationship with WMC, a significant correlation could be observed between WMC and aided speech recognition. However, this only applied to listeners with HAE of up to approximately three years, and a consistent weakening of the correlation could be observed with more experience. CONCLUSIONS: Speech recognition scores obtained in acute experiments with an MHA are less influenced by individual cognitive capacity when experienced HA users are taken into account.

Validating a Method to Assess Lipreading, Audiovisual Gain, and Integration During Speech Reception With Cochlear-Implanted and Normal-Hearing Subjects Using a Talking Head.

OBJECTIVES: Watching a talker's mouth is beneficial for speech reception (SR) in many communication settings, especially in noise and when hearing is impaired. Measures for audiovisual (AV) SR can be valuable in the framework of diagnosing or treating hearing disorders. This study addresses the lack of standardized methods in many languages for assessing lipreading, AV gain, and integration. A new method is validated that supplements a German speech audiometric test with visualizations of the synthetic articulation of an avatar that was used, for it is feasible to lip-sync auditory speech in a highly standardized way. Three hypotheses were formed according to the literature on AV SR that used live or filmed talkers. It was tested whether respective effects could be reproduced with synthetic articulation: (1) cochlear implant (CI) users have a higher visual-only SR than normal-hearing (NH) individuals, and younger individuals obtain higher lipreading scores than older persons. (2) Both CI and NH gain from presenting AV over unimodal (auditory or visual) sentences in noise. (3) Both CI and NH listeners efficiently integrate complementary auditory and visual speech features. DESIGN: In a controlled, cross-sectional study with 14 experienced CI users (mean age 47.4) and 14 NH individuals (mean age 46.3, similar broad age distribution), lipreading, AV gain, and integration of a German matrix sentence test were assessed. Visual speech stimuli were synthesized by the articulation of the Talking Head system "MASSY" (Modular Audiovisual Speech Synthesizer), which displayed standardized articulation with respect to the visibility of German phones. RESULTS: In line with the hypotheses and previous literature, CI users had a higher mean visual-only SR than NH individuals (CI, 38%; NH, 12%; p < 0.001). Age was correlated with lipreading such that within each group, younger individuals obtained higher visual-only scores than older persons (rCI = -0.54; p = 0.046; rNH = -0.78; p < 0.001). Both CI and NH benefitted by AV over unimodal speech as indexed by calculations of the measures visual enhancement and auditory enhancement (each p < 0.001). Both groups efficiently integrated complementary auditory and visual speech features as indexed by calculations of the measure integration enhancement (each p < 0.005). CONCLUSIONS: Given the good agreement between results from literature and the outcome of supplementing an existing validated auditory test with synthetic visual cues, the introduced method can be considered an interesting candidate for clinical and scientific applications to assess measures important for AV SR in a standardized manner. This could be beneficial for optimizing the diagnosis and treatment of individual listening and communication disorders, such as cochlear implantation.

Maturation of auditory brainstem responses in young children with congenital monaural atresia.

OBJECTIVE: To date, the impact of conductive hearing loss on the auditory pathway at brainstem level has only been investigated in animal studies, which showed a species-specific delay of maturation. In this study, the functional maturation of auditory brainstem response (ABR) parameters in humans with unilateral atresia of the external auditory canal was investigated. METHODS: 42 newborns and toddlers ranging in age from 13 days to 11 months were included. The click-evoked ABR interpeak latencies (IPL) of the atretic ears and the contralateral ears with normal hearing were evaluated. The children had no comorbidities and had never been fitted with any kind of hearing aid. The absolute latencies (AL) and IPL of a matched control group were compared to the contralateral normally hearing ears of the children with unilateral atresia. RESULTS: The mean air-bone gap in the ears with atresia was 44 dB HL. Despite this partial acoustic deprivation, no significant difference between the IPLs of normal ears and ears with atresia could be detected. Both for AL and IPL, the differences between the normal ears and the control group were all within 1 standard deviation to the mean. CONCLUSION: The data showed that the monaural acoustic deprivation by a block of sound conduction does not produce any delay of functional maturation at brainstem level in this group of patients. With regard to the AL and IPL on brainstem level, no differences between the normal ears of children with unilateral atresia and children with bilateral normal hearing could be detected.

Acute effects and after-effects of acoustic coordinated reset neuromodulation in patients with chronic subjective tinnitus.

Chronic subjective tinnitus is an auditory phantom phenomenon characterized by abnormal neuronal synchrony in the central auditory system. As shown computationally, acoustic coordinated reset (CR) neuromodulation causes a long-lasting desynchronization of pathological synchrony by downregulating abnormal synaptic connectivity. In a previous proof of concept study acoustic CR neuromodulation, employing stimulation tone patterns tailored to the dominant tinnitus frequency, was compared to noisy CR-like stimulation, a CR version significantly detuned by sparing the tinnitus-related pitch range and including substantial random variability of the tone spacing on the frequency axis. Both stimulation protocols caused an acute relief as measured with visual analogue scale scores for tinnitus loudness (VAS-L) and annoyance (VAS-A) in the stimulation-ON condition (i.e. 15 min after stimulation onset), but only acoustic CR neuromodulation had sustained long-lasting therapeutic effects after 12 weeks of treatment as assessed with VAS-L, VAS-A scores and a tinnitus questionnaire (TQ) in the stimulation-OFF condition (i.e. with patients being off stimulation for at least 2.5 h). To understand the source of the long-lasting therapeutic effects, we here study whether acoustic CR neuromodulation has different electrophysiological effects on oscillatory brain activity as compared to noisy CR-like stimulation under stimulation-ON conditions and immediately after cessation of stimulation. To this end, we used a single-blind, single application, cross over design in 18 patients with chronic tonal subjective tinnitus and administered three different 16-minute stimulation protocols: acoustic CR neuromodulation, noisy CR-like stimulation and low frequency range (LFR) stimulation, a CR type stimulation with deliberately detuned pitch and repetition rate of stimulation tones, as control stimulation. We measured VAS-L and VAS-A scores together with spontaneous EEG activity pre-, during- and post-stimulation. Under stimulation-ON conditions acoustic CR neuromodulation and noisy CR-like stimulation had similar effects: a reduction of VAS-L and VAS-A scores together with a decrease of auditory delta power and an increase of auditory alpha and gamma power, without significant differences. In contrast, LFR stimulation had significantly weaker EEG effects and no significant clinical effects under stimulation-ON conditions. The distinguishing feature between acoustic CR neuromodulation and noisy CR-like stimulation were the electrophysiological after-effects. Acoustic CR neuromodulation caused the longest significant reduction of delta and gamma and increase of alpha power in the auditory cortex region. Noisy CR-like stimulation had weaker and LFR stimulation hardly any electrophysiological after-effects. This qualitative difference further supports the assertion that long-term effects of acoustic CR neuromodulation on tinnitus are mediated by a specific disruption of synchronous neural activity. Furthermore, our results indicate that acute electrophysiological after-effects might serve as a marker to further improve desynchronizing sound stimulation.

AUNA2: A Novel Type of Non-Syndromic Slowly Progressive Auditory Synaptopathy/Auditory Neuropathy with Autosomal-Dominant Inheritance.

BACKGROUND: Auditory synaptopathy/neuropathy (AS/AN) is a heterogeneous disorder, which may be caused by environmental factors like postnatal hyperbilirubinemia or by genetic factors. The genetic forms are subdivided into syndromic and non-syndromic types, and show different inheritance patterns with a strong preponderance of autosomal-recessive forms. To date, only a single locus for non-syndromic autosomal-dominant AS/AN (AUNA1) has been reported in a single family, in which a non-coding DIAPH3 mutation was subsequently described as causative. MATERIALS AND METHODS: Here, we report detailed clinical data on a large German AS/AN family with slowly progressive postlingual hearing loss. Affected family members developed their first symptoms in their second decade. Moderate hearing loss in the fourth decade then progressed to profound hearing impairment in older family members. Comprehensive audiological and neurological tests were performed in the affected family members. Genetic testing comprised linkage analyses with polymorphic markers and a genome-wide linkage analysis using the Affymetrix GeneChip® Human Mapping 250K. RESULTS AND CONCLUSION: We identified a large family with autosomal-dominant AS/AN. By means of linkage analyses, the AUNA1 locus was excluded, and putatively linked regions on chromosomal bands 12q24 and 13q34 were identified as likely carrying the second locus for autosomal-dominant AS/AN (AUNA2). AUNA2 is associated with a slowly progressive postlingual hearing loss without any evidence for additional symptoms in other organ systems.