Effects of tonotopic matching and spatial cues on segregation of competing speech in simulations of bilateral cochlear implants.

In the clinical fitting of cochlear implants (CIs), the lowest input acoustic frequency is typically much lower than the characteristic frequency associated with the most apical electrode position, due to the limited electrode insertion depth. For bilateral CI users, electrode positions may differ across ears. However, the same acoustic-to-electrode frequency allocation table (FAT) is typically assigned to both ears. As such, bilateral CI users may experience both intra-aural frequency mismatch within each ear and inter-aural mismatch across ears. This inter-aural mismatch may limit the ability of bilateral CI users to take advantage of spatial cues when attempting to segregate competing speech. Adjusting the FAT to tonotopically match the electrode position in each ear (i.e., increasing the low acoustic input frequency) is theorized to reduce this inter-aural mismatch. Unfortunately, this approach may also introduce the loss of acoustic information below the modified input acoustic frequency. The present study explored the trade-off between reduced inter-aural frequency mismatch and low-frequency information loss for segregation of competing speech. Normal-hearing participants were tested while listening to acoustic simulations of bilateral CIs. Speech reception thresholds (SRTs) were measured for target sentences produced by a male talker in the presence of two different male talkers. Masker speech was either co-located with or spatially separated from the target speech. The bilateral CI simulations were produced by 16-channel sinewave vocoders; the simulated insertion depth was fixed in one ear and varied in the other ear, resulting in an inter-aural mismatch of 0, 2, or 6 mm in terms of cochlear place. Two FAT conditions were compared: 1) clinical (200-8000 Hz in both ears), or 2) matched to the simulated insertion depth in each ear. Results showed that SRTs were significantly lower with the matched than with the clinical FAT, regardless of the insertion depth or spatial configuration of the masker speech. The largest improvement in SRTs with the matched FAT was observed when the inter-aural mismatch was largest (6 mm). These results suggest that minimizing inter-aural mismatch with tonotopically matched FATs may benefit bilateral CI users' ability to segregate competing speech despite substantial low-frequency information loss in ears with shallow insertion depths.

Selective scalp block decreases short term post-operative pain scores and opioid use after craniotomy: A case series.

There is no consensus on the management of post-craniotomy pain. Several randomized controlled trials have examined the use of a regional scalp block for post-craniotomy pain. We aim to investigate whether scalp block affected short or long-term pain levels and opioid use after craniotomy. This study prospectively administered selective scalp blocks (lesser occipital, preauricular nerve block + pin site block) in 20 consecutive patients undergoing craniotomy for semicircular canal dehiscence. Anesthesia, pain, and opioid outcomes in these patients were compared to 40 consecutive historic controls. There was no significant difference in patient demographics between the two groups and no complications related to selective scalp block. The time between the end of procedure and end of anesthesia decreased in the scalp block group (16 vs 21 min, P = 0.047). Pain scores were significantly less in the scalp block group for the first 4 h, after which there was no statistically significant difference. Time to opioid rescue was longer in the scalp block group (3.6 vs 1.8 h, HR 0.487, P = 0.0361) and opioid use in the first 7 h was significantly less in the scalp block group. Total opioid use, outpatient opioid use, and length of stay did not differ. Selective scalp block is a safe and effective tool for short-term management of postoperative pain after craniotomy and decreases the medication requirement during emergence and recovery. Selective scalp block can speed up OR turnover but is not efficacious in the treatment of postoperative pain beyond this point.

Superior Semicircular Canal Dehiscence Outcomes in a Consecutive Series of 229 Surgical Repairs With Middle Cranial Fossa Craniotomy.

BACKGROUND: Superior semicircular canal dehiscence (SSCD) is the appearance of a third mobile window between the middle fossa and the superior semicircular canal. Surgical management is indicated in patients with persistent and debilitating symptoms. The purpose of this study was to evaluate the association between preoperative variables that may impact postoperative symptomatic resolution. METHODS: A single-institution retrospective analysis was performed on patients who were surgically treated for SSCD. Patients were divided to different cohorts based on unilateral or bilateral nature of the disease. A P value <0.05 was considered statistically significant. RESULTS: A total of 229 surgical repairs were analyzed. Mean age was 51 years (± 7.8 years), and 55.9% of patients were female. All cohorts were similar with respect to baseline demographics. The most commonly reported preoperative symptoms were tinnitus, dizziness, and autophony. The greatest symptomatic resolution was seen in autophony, internal sound amplification, hyperacusis, and oscillopsia. The unilateral SSCD cohort had significantly higher improvement of autophony (P = 0.003), aural fullness (P = 0.05), tinnitus (P = 0.006), hearing loss (P = 0.02), dizziness (P = 0.006), and headache (P = 0.007), compared with the bilateral SSCD cohorts. Among patients with bilateral disease, those with unilateral surgery reported greater symptomatic resolution with respect to hyperacusis (P = 0.03), hearing loss (P = 0.02), dizziness (P = 0.03), and disequilibrium (P < 0.001), than those with bilateral operations. CONCLUSIONS: Surgical management of SSCD leads to high rates of postoperative symptomatic improvement. Patients with unilateral SSCD benefit greater symptomatic resolution compared to those with bilateral pathology.

Novel grading system of sigmoid sinus dehiscence for radiologic evaluation of pulsatile tinnitus.

BACKGROUND: Sigmoid sinus dehiscence (SSD) is an important etiology of pulsatile tinnitus (PT) though there is currently no consensus on the prevalence of SSD in non-PT populations. This study establishes a grading system of SSD and analyzes a non-PT cohort for prevalence of SSD. METHODS: In this retrospective study temporal bone CT scans of 91 patients without PT were analyzed for SSD. The dehiscence was divided into three grades: Grade 1 indicating a micro dehiscence of <3.5 mm with an opening to the mastoid air cells, Grade 2 indicating a major dehiscence of >3.5 mm with an opening to the mastoid air cells, and Grade 3 indicating a sigmoid sinus wall dehiscence opening directly to the underlying tissue. RESULTS: In patients without PT, SSD occurred in 34% of the cohort. Of these, 75% were Grade 1 and 25% were Grade 2. The range of dehiscence measurements for Grade 1 dehiscences was 0.9-3.4 mm. The range of dehiscence measurements for Grade 2 was 4-7.5 mm. There were no cases of Grade 3 dehiscence among this cohort. CONCLUSIONS: SSD occurred in over a third of our non-symptomatic cohort. While all grades of SSD may currently be treated surgically, a large portion of non-PT patients may have these sigmoid sinus anomalies asymptomatically. This grading system allows for the standardization of SSD definition and severity in future studies. Grade 3 dehiscences were completely absent in this cohort of non-PT patients.

Bilateral and bimodal cochlear implant listeners can segregate competing speech using talker sex cues, but not spatial cues.

Cochlear implant (CI) users have greater difficulty perceiving talker sex and spatial cues than do normal-hearing (NH) listeners. The present study measured recognition of target sentences in the presence of two co-located or spatially separated speech maskers in NH, bilateral CI, and bimodal CI listeners; masker sex was the same as or different than the target. NH listeners demonstrated a large masking release with masker sex and/or spatial cues. For CI listeners, significant masking release was observed with masker sex cues, but not with spatial cues, at least for the spatially symmetrically placed maskers and listening task used in this study.

Analysis of temporal bone thickness outside of the petrous temporal bone between superior semicircular canal dehiscence and normal patients.

BACKGROUND: SSCD is a rare inner ear disorder. This study aims to compare the thickness of the temporal bone beyond the petrous portion between healthy subjects and those with SSCD to determine whether the etiopathology of SSCD is localized to the petrous temporal bone or generalized to other parts of the temporal bone. METHODS: A retrospective chart review of electronic medical records from September 2011 to February 2018 was conducted at a single-institution study at the University of California, Los Angeles. Participants were divided into two groups: Group 1 had a confirmed diagnosis of SSCD, while Group 2 had no known ear or temporal bone pathology. Participants' high-resolution coronal and axial temporal bone computed tomography scans were analyzed. Regions within the temporal bone were measured and compared between the two groups. RESULTS: A total of 262 scans were included. Group 1 consisted of 103 scans, while Group 2 consisted of 159 scans. There was no statistically significant difference in the thickness of temporal bones between patients diagnosed with SSCD and patients without otologic disease. CONCLUSION: The results suggest that the etiology of SSCD is limited to the petrous portion of the temporal bone. SSCD may be unrelated to a larger process of global temporal bone degeneration. Additional clinical screening for regions outside the petrous temporal bone is not warranted unless SSCD patients present with symptoms characteristic of other temporal bone pathologies.

Concurrent superior semicircular canal dehiscence and endolymphatic hydrops: A novel case series.

INTRODUCTION: Superior semicircular canal dehiscence (SSCD) is characterized by CT-confirmed bony erosion over the superior semicircular canal, creating vestibular and auditory symptoms. Endolymphatic hydrops (EH) is characterized by an MRI-confirmed excess of endolymph within the scala media that distorts the membranous labyrinth. While there is overlap in symptoms, the two diseases result from different pathophysiologies and require different interventions. PRESENTATION OF CASES: A retrospective chart review was conducted at the University of California, Los Angeles on a database of 270 adult SSCD patients, gathered between March 2011 and February 2020. A review of clinical notes, post-operative findings, and imaging was performed for 16 patients who had both CT-confirmed SSCD and an MRI of the internal auditory canal (IAC). Three cases of concurrent SSCD and EH were identified. Medical and surgical history, symptom progression pre- and post-operatively, and treatment outcomes were gathered. One patient's symptoms were resolved via mycophenolate mofetil, another's via hydrochlorothiazide, and the third's via hydrochlorothiazide and bilateral hearing aids. DISCUSSION: Post-surgical persistence of SSCD symptoms that are mutually shared with EH is the strongest indicator that a physician should investigate for concurrent EH. VEMP and audiogram testing in these cases can be misleading and should not be relied on as rule-in or rule-out tests. CONCLUSION: Concurrent SSCD and EH is a rare but treatable entity. Physicians should consider ordering an MRI of the IAC if SSCD patients' symptoms persist or recur after a successful surgery.

Effects of noise on integration of acoustic and electric hearing within and across ears.

In bimodal listening, cochlear implant (CI) users combine electric hearing (EH) in one ear and acoustic hearing (AH) in the other ear. In electric-acoustic stimulation (EAS), CI users combine EH and AH in the same ear. In quiet, integration of EH and AH has been shown to be better with EAS, but with greater sensitivity to tonotopic mismatch in EH. The goal of the present study was to evaluate how external noise might affect integration of AH and EH within or across ears. Recognition of monosyllabic words was measured for normal-hearing subjects listening to simulations of unimodal (AH or EH alone), EAS, and bimodal listening in quiet and in speech-shaped steady noise (10 dB, 0 dB signal-to-noise ratio). The input/output frequency range for AH was 0.1-0.6 kHz. EH was simulated using an 8-channel noise vocoder. The output frequency range was 1.2-8.0 kHz to simulate a shallow insertion depth. The input frequency range was either matched (1.2-8.0 kHz) or mismatched (0.6-8.0 kHz) to the output frequency range; the mismatched input range maximized the amount of speech information, while the matched input resulted in some speech information loss. In quiet, tonotopic mismatch differently affected EAS and bimodal performance. In noise, EAS and bimodal performance was similarly affected by tonotopic mismatch. The data suggest that tonotopic mismatch may differently affect integration of EH and AH in quiet and in noise.

Tonal Language Speakers Are Better Able to Segregate Competing Speech According to Talker Sex Differences.

Purpose The aim of this study was to compare release from masking (RM) between Mandarin-speaking and English-speaking listeners with normal hearing for competing speech when target-masker sex cues, spatial cues, or both were available. Method Speech recognition thresholds (SRTs) for competing speech were measured in 21 Mandarin-speaking and 15 English-speaking adults with normal hearing using a modified coordinate response measure task. SRTs were measured for target sentences produced by a male talker in the presence of two masker talkers (different male talkers or female talkers). The target sentence was always presented directly in front of the listener, and the maskers were either colocated with the target or were spatially separated from the target (+90°, -90°). Stimuli were presented via headphones and were virtually spatialized using head-related transfer functions. Three masker conditions were used to measure RM relative to the baseline condition: (a) talker sex cues, (b) spatial cues, or (c) combined talker sex and spatial cues. Results The results showed large amounts of RM according to talker sex and/or spatial cues. There was no significant difference in SRTs between Chinese and English listeners for the baseline condition, where no talker sex or spatial cues were available. Furthermore, there was no significant difference in RM between Chinese and English listeners when spatial cues were available. However, RM was significantly larger for Chinese listeners when talker sex cues or combined talker sex and spatial cues were available. Conclusion Listeners who speak a tonal language such as Mandarin Chinese may be able to take greater advantage of talker sex cues than listeners who do not speak a tonal language.

Human Influenza Virus Hemagglutinins Contain Conserved Oligomannose N-Linked Glycans Allowing Potent Neutralization by Lectins.

Hemagglutinins (HAs) from human influenza viruses adapt to bind α2-6-linked sialosides, overcoming a receptor-defined species barrier distinct from the α2-3 specificity of avian virus progenitors. Additionally, human-adapted HAs gain glycosylation sites over time, although their biological function is poorly defined. Using quantitative glycomic analysis, we show that HAs from human pandemic viruses exhibit significant proportions of high-mannose type N-linked glycans throughout the head domain. By contrast, poorly adapted avian-origin HAs contain predominately complex-type glycans, which have greater structural diversity. Although oligomannose levels vary, they are present in all tested recombinant HAs and whole viruses and can be specifically targeted for universal detection. The positions of high-mannose glycosites on the HA of human H1N1 and H3N2 strains are conserved. Additionally, high-mannose-binding lectins possess a broad capacity to neutralize and prevent infection with contemporary H3N2 strains. These findings reveal the biological significance of HA glycosylation and therapeutic potential of targeting these structures.

Effects of Spectral Resolution and Frequency Mismatch on Speech Understanding and Spatial Release From Masking in Simulated Bilateral Cochlear Implants.

OBJECTIVES: Due to interaural frequency mismatch, bilateral cochlear-implant (CI) users may be less able to take advantage of binaural cues that normal-hearing (NH) listeners use for spatial hearing, such as interaural time differences and interaural level differences. As such, bilateral CI users have difficulty segregating competing speech even when the target and competing talkers are spatially separated. The goal of this study was to evaluate the effects of spectral resolution, tonotopic mismatch (the frequency mismatch between the acoustic center frequency assigned to CI electrode within an implanted ear relative to the expected spiral ganglion characteristic frequency), and interaural mismatch (differences in the degree of tonotopic mismatch in each ear) on speech understanding and spatial release from masking (SRM) in the presence of competing talkers in NH subjects listening to bilateral vocoder simulations. DESIGN: During testing, both target and masker speech were presented in five-word sentences that had the same syntax but were not necessarily meaningful. The sentences were composed of five categories in fixed order (Name, Verb, Number, Color, and Clothes), each of which had 10 items, such that multiple sentences could be generated by randomly selecting a word from each category. Speech reception thresholds (SRTs) for the target sentence presented in competing speech maskers were measured. The target speech was delivered to both ears and the two speech maskers were delivered to (1) both ears (diotic masker), or (2) different ears (dichotic masker: one delivered to the left ear and the other delivered to the right ear). Stimuli included the unprocessed speech and four 16-channel sine-vocoder simulations with different interaural mismatch (0, 1, and 2 mm). SRM was calculated as the difference between the diotic and dichotic listening conditions. RESULTS: With unprocessed speech, SRTs were 0.3 and -18.0 dB for the diotic and dichotic maskers, respectively. For the spectrally degraded speech with mild tonotopic mismatch and no interaural mismatch, SRTs were 5.6 and -2.0 dB for the diotic and dichotic maskers, respectively. When the tonotopic mismatch increased in both ears, SRTs worsened to 8.9 and 2.4 dB for the diotic and dichotic maskers, respectively. When the two ears had different tonotopic mismatch (e.g., there was interaural mismatch), the performance drop in SRTs was much larger for the dichotic than for the diotic masker. The largest SRM was observed with unprocessed speech (18.3 dB). With the CI simulations, SRM was significantly reduced to 7.6 dB even with mild tonotopic mismatch but no interaural mismatch; SRM was further reduced with increasing interaural mismatch. CONCLUSIONS: The results demonstrate that frequency resolution, tonotopic mismatch, and interaural mismatch have differential effects on speech understanding and SRM in simulation of bilateral CIs. Minimizing interaural mismatch may be critical to optimize binaural benefits and improve CI performance for competing speech, a typical listening environment. SRM (the difference in SRTs between diotic and dichotic maskers) may be a useful clinical tool to assess interaural frequency mismatch in bilateral CI users and to evaluate the benefits of optimization methods that minimize interaural mismatch.

Antibody Responses to Immunization With HCV Envelope Glycoproteins as a Baseline for B-Cell-Based Vaccine Development.

BACKGROUND & AIMS: We investigated antibody responses to hepatitis C virus (HCV) antigens E1 and E2 and the relevance of animal models for vaccine development. We compared antibody responses to vaccination with recombinant E1E2 complex in healthy volunteers, non-human primates (NHPs), and mice. METHODS: We analyzed 519 serum samples from participants in a phase 1 vaccine trial (ClinicalTrials.gov identifier NCT00500747) and compared them with serum or plasma samples from C57BL/6J mice (n = 28) and rhesus macaques (n = 4) immunized with the same HCV E1E2 antigen. Blood samples were collected at different time points and analyzed for antibody binding, neutralizing activity, and epitope specificity. Monoclonal antibodies from the immunized NHPs were isolated from single plasmablasts and memory B cells, and their immunogenetic properties were characterized. RESULTS: Antibody responses of the volunteers, NHPs, and mice to the non-neutralizing epitopes on the E1 N-terminus and E2 hypervariable region 1 did not differ significantly. Antibodies from volunteers and NHPs that neutralized heterologous strains of HCV primarily interacted with epitopes in the antigen region 3. However, the neutralizing antibodies were not produced in sufficient levels for broad neutralization of diverse HCV isolates. Broadly neutralizing antibodies similar to the human VH1-69 class antibody specific for antigen region 3 were produced in the immunized NHPs. CONCLUSIONS: In an analysis of vaccinated volunteers, NHPs, and mice, we found that recombinant E1E2 vaccine antigen induces high-antibody titers that are insufficient to neutralize diverse HCV isolates. Antibodies from volunteers and NHPs bind to the same neutralizing epitopes for virus neutralization. NHPs can therefore be used as a preclinical model to develop HCV vaccines. These findings also provide useful baseline values for development of vaccines designed to induce production of neutralizing antibodies.