Striatal networks for tinnitus treatment targeting.

Neuromodulation treatment effect size for bothersome tinnitus may be larger and more predictable by adopting a target selection approach guided by personalized striatal networks or functional connectivity maps. Several corticostriatal mechanisms are likely to play a role in tinnitus, including the dorsal/ventral striatum and the putamen. We examined whether significant tinnitus treatment response by deep brain stimulation (DBS) of the caudate nucleus may be related to striatal network increased functional connectivity with tinnitus networks that involve the auditory cortex or ventral cerebellum. The first study was a cross-sectional 2-by-2 factorial design (tinnitus, no tinnitus; hearing loss, normal hearing, n = 68) to define cohort level abnormal functional connectivity maps using high-field 7.0 T resting-state fMRI. The second study was a pilot case-control series (n = 2) to examine whether tinnitus modulation response to caudate tail subdivision stimulation would be contingent on individual level striatal connectivity map relationships with tinnitus networks. Resting-state fMRI identified five caudate subdivisions with abnormal cohort level functional connectivity maps. Of those, two connectivity maps exhibited increased connectivity with tinnitus networks-dorsal caudate head with Heschl's gyrus and caudate tail with the ventral cerebellum. DBS of the caudate tail in the case-series responder resulted in dramatic reductions in tinnitus severity and loudness, in contrast to the nonresponder who showed no tinnitus modulation. The individual level connectivity map of the responder was in alignment with the cohort expectation connectivity map, where the caudate tail exhibited increased connectivity with tinnitus networks, whereas the nonresponder individual level connectivity map did not.

Interhemispheric Auditory Cortical Synchronization in Asymmetric Hearing Loss.

OBJECTIVES: Auditory cortical activation of the two hemispheres to monaurally presented tonal stimuli has been shown to be asynchronous in normal hearing (NH) but synchronous in the extreme case of adult-onset asymmetric hearing loss (AHL) with single-sided deafness. We addressed the wide knowledge gap between these two anchoring states of interhemispheric temporal organization. The objectives of this study were as follows: (1) to map the trajectory of interhemispheric temporal reorganization from asynchrony to synchrony using magnitude of interaural threshold difference as the independent variable in a cross-sectional study and (2) to evaluate reversibility of interhemispheric synchrony in association with hearing in noise performance by amplifying the aidable poorer ear in a repeated measures, longitudinal study. DESIGN: The cross-sectional and longitudinal cohorts were comprised of 49 subjects (AHL; N = 21; 11 male, 10 female; mean age = 48 years) and NH (N = 28; 16 male, 12 female; mean age = 45 years). The maximum interaural threshold difference of the two cohorts spanned from 0 to 65 dB. Magnetoencephalography analyses focused on latency of the M100 peak response from auditory cortex in both hemispheres between 50 msec and 150 msec following monaural tonal stimulation at the frequency (0.5, 1, 2, 3, or 4 kHz) corresponding to the maximum and minimum interaural threshold difference for better and poorer ears separately. The longitudinal AHL cohort was drawn from three subjects in the cross-sectional AHL cohort (all male; ages 49 to 60 years; varied AHL etiologies; no amplification for at least 2 years). All longitudinal study subjects were treated by monaural amplification of the poorer ear and underwent repeated measures examination of the M100 response latency and quick speech in noise hearing in noise performance at baseline, and postamplification months 3, 6, and 12. RESULTS: The M100 response peak latency values in the ipsilateral hemisphere lagged those in the contralateral hemisphere for all stimulation conditions. The mean (SD) interhemispheric latency difference values (ipsilateral less contralateral) to better ear stimulation for three categories of maximum interaural threshold difference were as follows: NH (≤ 10 dB)-8.6 (3.0) msec; AHL (15 to 40 dB)-3.0 (1.2) msec; AHL (≥ 45 dB)-1.4 (1.3) msec. In turn, the magnitude of difference values were used to define interhemispheric temporal organization states of asynchrony, mixed asynchrony and synchrony, and synchrony, respectively. Amplification of the poorer ear in longitudinal subjects drove interhemispheric organization change from baseline synchrony to postamplification asynchrony and hearing in noise performance improvement in those with baseline impairment over a 12-month period. CONCLUSIONS: Interhemispheric temporal organization in AHL was anchored between states of asynchrony in NH and synchrony in single-sided deafness. For asymmetry magnitudes between 15 and 40 dB, the intermediate mixed state of asynchrony and synchrony was continuous and reversible. Amplification of the poorer ear in AHL improved hearing in noise performance and restored normal temporal organization of auditory cortices in the two hemispheres. The return to normal interhemispheric asynchrony from baseline synchrony and improvement in hearing following monoaural amplification of the poorer ear evolved progressively over a 12-month period.

Global resting-state functional connectivity of neural oscillations in tinnitus with and without hearing loss.

This study examined global resting-state functional connectivity of neural oscillations in individuals with chronic tinnitus and normal and impaired hearing. We tested the hypothesis that distinct neural oscillatory networks are engaged in tinnitus with and without hearing loss. In both tinnitus groups, with and without hearing loss, we identified multiple frequency band-dependent regions of increased and decreased global functional connectivity. We also found that the auditory domain of tinnitus severity, assayed by the Tinnitus Functional Index, was associated with global functional connectivity in both auditory and nonauditory regions. These findings provide candidate biomarkers to target and monitor treatments for tinnitus with and without hearing loss.

A Smartphone Application and Education Program for Hearing Health Promotion in High School Teenagers.

OBJECTIVES: To assess knowledge retention after video-based hearing health education and measure headphone listening behavior change using a novel smartphone application. METHODS: In this prospective longitudinal study, students participated in video-based hearing health education and hearing screening sessions. Hearing health knowledge was assessed in students and parents after 6 weeks. A novel smartphone application was created to measure daily noise exposure based on volume settings with headphone use and to display the National Institute for Occupational Safety and Health (NIOSH) noise doses with alerts for cumulative daily doses nearing the maximum. RESULTS: Seventy-six teenage students and parents participated. Eighty three percent of participants identified as a racial or ethnic minority and 66% were of low-income socioeconomic status. Hearing health knowledge was retained in students 6 weeks after education and parents' knowledge improved from baseline. The smartphone app was installed on 12 student phones, and 25% of days monitored exhibited noise doses that exceeded the NIOSH maximum. App use for at least 10 days by nine students showed a significant reduction in average daily noise dose and time spent at the highest volume settings during the second-half of app use. CONCLUSIONS: Video-based hearing health education with knowledge question reinforcement was associated with knowledge retention in students and improved parental attitudes and knowledge about hearing conservation. A smartphone app with a real-time display of headphone cumulative noise exposure dose identified at-risk students. The integration of hearing health education, hearing screening, and digital health tools has promised to promote positive behavior changes for long-term hearing conservation. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2007-2013, 2023.

Cancer survivors and neurotoxic chemotherapy: hearing loss and tinnitus.

OBJECTIVES: Little is known about hearing loss and tinnitus associated with neurotoxic chemotherapy. Study evaluated for differences in occurrence rates and effects of hearing loss and tinnitus in survivors who received a platinum alone, a taxane alone or a platinum and taxane containing regimen. METHODS: Total of 273 survivors with breast, gastrointestinal, gynaecological or lung cancer completed self-report measures of hearing loss and tinnitus and had an audiometric assessment that obtained pure tone air conduction thresholds bilaterally at frequencies of between 0.25 kHz to 16.0 kHz. To adjust for age-related and gender-related changes in hearing, each survivor's audiogram was evaluated using the National Health and Nutrition Examination Survey-modified Occupational Safety and Health Administration standards. Survivor was classified as having hearing loss if at any frequency they scored poorer than the 50th percentile for their age and gender. Survivors were categorised as having tinnitus if they reported that for >10% of their time awake, they were consciously aware of their tinnitus. Differences among the chemotherapy groups were evaluated using parametric and non-parametric tests. RESULTS: For most of the demographic and clinical characteristics, no differences were found among the three chemotherapy groups. Occurrence rates for audiogram-confirmed hearing loss ranged from 52.3% to 71.4%. Occurrence rates for tinnitus ranged from 37.1% to 40.0%. No differences were found among the three chemotherapy groups in the occurrence rates or effects of hearing loss and tinnitus. CONCLUSION: These findings suggest that regardless of the chemotherapy regimen common mechanistic pathway(s) may underlie these two neurotoxicities.

Aging Affects Subcortical Pitch Information Encoding Differently in Humans With Different Language Backgrounds.

Aging and language background have been shown to affect pitch information encoding at the subcortical level. To study the individual and compounded effects on subcortical pitch information encoding, Frequency Following Responses were recorded from subjects across various ages and language backgrounds. Differences were found in pitch information encoding strength and accuracy among the groups, indicating that language experience and aging affect accuracy and magnitude of pitch information encoding ability at the subcortical level. Moreover, stronger effects of aging were seen in the magnitude of phase-locking in the native language speaker groups, while language background appears to have more impact on the accuracy of pitch tracking in older adult groups.

Similarities in the Neuropathy Phenotype of Cancer Survivors Who Received Different Classes of Chemotherapy Drugs.

With the advent of platinum and taxane compounds used as single agents or in combination regimens, survival rates for some of the most common cancers have improved substantially. However, information on differences in the chemotherapy-induced peripheral neuropathy (CIPN) phenotype among single and combination regimens is limited. Study's purposes were to evaluate for differences in demographic and clinical characteristics; subjective and objective measures of CIPN; as well as the severity of common symptoms and quality of life among survivors who received platinum- (n = 95), taxane- (n = 200), or platinum and taxane-containing (n = 131) regimens. Patients completed self-report questionnaires (ie, duration of CIPN, pain intensity, pain qualities, pain interference) and underwent a physical examination that evaluated light touch, pain, and cold sensations and balance. For most of the subjective and objective measures of CIPN, as well as symptom severity and quality of life scores, no differences were found among the 3 chemotherapy groups. In all 3 chemotherapy treatment groups, CIPN was a painful, small fiber, and length dependent neuropathy. These findings support the hypothesis that CIPN induced by different classes of chemotherapy, as single agents or in combination, produce a similar CIPN phenotype which raises the possibility that CIPN induced by diverse chemotherapy protocols has the same underlying mechanism. PERSPECTIVE: In this study, that compared patients who received only platinum, only taxane, or both platinum and taxane containing regimens, no differences were found among the 3 groups in the CIPN phenotype. Findings raise the possibility that CIPN induced by diverse chemotherapy protocols has the same underlying mechanism.

Treated large posterior fossa vestibular schwannoma and meningioma: Hearing outcome and willingness-to-accept brain implant for unilateral deafness.

Background/Objective: To compare functional hearing and tinnitus outcomes in treated large (~ 3 cm) vestibular schwannoma (VS) and posterior fossa meningioma cohorts, and construct willingness-to-accept profiles for an experimental brain implant to treat unilateral hearing loss. Methods: A two-way MANOVA model with two independent variables (tumor type; time from treatment) and three dependent variables (hearing effort of tumor ear; abbreviated Speech, Spatial, and Qualities of Hearing scale (SSQ12); Tinnitus Functional Index (TFI)) was used to analyze data from VS (N = 32) and meningioma (N = 50) patients who were treated at a tertiary care center between 2010 and 2020. A query to probe acceptance of experimental treatment for hearing loss relative to expected benefit was used to construct willingness-to-accept profiles. Results: Tumor type was statistically significant on the combined dependent variables analysis (F[3, 76] = 19.172, p < .0005, Wilks' Λ = 0.569). Meningioma showed better outcome for hearing effort (F[1, 76] = 14.632, p < .0005) and SSQ12 (F[1, 76] = 16.164, p < .0005), but not for TFI (F[1, 76] = 1.247, p = .268) on univariate two-way ANOVA analyses. Superior hearing effort and SSQ12 indices in the short-term (< 2 years) persisted in the long-term (> 2 years) (p ≤ .017). At the 60% speech understanding level, 77% of respondents would accept an experimental brain implant. Conclusion: Hearing outcome is better for posterior fossa meningioma compared to VS. Most patients with hearing loss in the tumor ear would consider a brain implant if the benefit level would be comparable to a cochlear implant. Level of Evidence: 2.

Ear Preference and Interaural Threshold Asymmetry.

OBJECTIVE: To define the relationships among ear preference strength, audiometric interaural asymmetry magnitude, and hearing impairment. STUDY DESIGN: Prospective, cross-sectional. SETTING: Academic audiology clinic. PATIENTS: Adults. INTERVENTIONS: Diagnostic. MAIN OUTCOME MEASURES: Patient-reported ear preference strength using a seven-category preference (no preference; left or right somewhat, strongly, or completely) scheme, hearing disability level on the Speech, Spatial, and Qualities of Hearing scale, and audiometric interaural threshold asymmetry were analyzed in three study cohorts: 1) normal hearing (thresholds ≤ 25 dB, n = 66), 2) symmetric hearing loss (any single threshold > 25 dB, n = 81), and 3) asymmetric hearing loss (maximum average interaural threshold difference at any two adjacent frequencies (IThrDmax2)≥ 15 dB, n = 112). RESULTS: Receiver operating characteristic curves for somewhat, strongly, and completely ear preference levels using IThrDmax2 cutoff values at 15, 30, and 45 dB showed good to excellent classifier performance (all curve areas ≥ 0.84). The mapping of ear preference strength to the most likely IThrDmax2 range by odds ratio analysis demonstrated: no preference (< 15 dB), somewhat (15-29 dB), strongly (30-44 dB), and completely (≥ 45 dB). Complete dependence on one ear was associated with the most severe degradation in spatial hearing function. CONCLUSION: Categorical ratings of ear preference strength may be mapped to ranges of audiometric threshold asymmetry magnitude and spatial hearing disability level. Querying ear preference strength in routine clinical practice would enable practitioners to identify patients with asymmetric hearing more expeditiously and promote timely evaluation and treatment.

Automated Smartphone Audiometry: A Preliminary Validation of a Bone-Conduction Threshold Test App.

OBJECTIVE: To develop and validate an automated smartphone app that determines bone-conduction pure-tone thresholds. METHODS: A novel app, called EarBone, was developed as an automated test to determine best-cochlea pure-tone bone-conduction thresholds using a smartphone driving a professional-grade bone oscillator. Adult, English-speaking patients who were undergoing audiometric assessment by audiologists at an academic health system as part of their prescribed care were invited to use the EarBone app. Best-ear bone-conduction thresholds determined by the app and the gold standard audiologist were compared. RESULTS: Forty subjects with varied hearing thresholds were tested. Sixty-one percent of app-determined thresholds were within 5 dB of audiologist-determined thresholds, and 79% were within 10 dB. Nearly all subjects required assistance with placing the bone oscillator on their mastoid. CONCLUSION: Best-cochlea bone-conduction thresholds determined by the EarBone automated smartphone audiometry app approximate those determined by an audiologist. This serves as a proof of concept for automated smartphone-based bone-conduction threshold testing. Further improvements, such as the addition of contralateral ear masking, are needed to make the app clinically useful.

Corticostriatal functional connectivity of bothersome tinnitus in single-sided deafness.

Subjective tinnitus is an auditory phantom perceptual disorder without an objective biomarker. Bothersome tinnitus in single-sided deafness (SSD) is particularly challenging to treat because the deaf ear can no longer be stimulated by acoustic means. We contrasted an SSD cohort with bothersome tinnitus (TIN; N = 15) against an SSD cohort with no or non-bothersome tinnitus (NO TIN; N = 15) using resting-state functional magnetic resonance imaging (fMRI). All study participants had normal hearing in one ear and severe or profound hearing loss in the other. We evaluated corticostriatal functional connectivity differences by placing seeds in the caudate nucleus and Heschl's Gyrus (HG) of both hemispheres. The TIN cohort showed increased functional connectivity between the left caudate and left HG, and left and right HG and the left caudate. Within the TIN cohort, functional connectivity between the right caudate and cuneus was correlated with the Tinnitus Functional Index (TFI) relaxation subscale. And, functional connectivity between the right caudate and superior lateral occipital cortex, and the right caudate and anterior supramarginal gyrus were correlated with the TFI control subscale. These findings support a striatal gating model of tinnitus and suggest tinnitus biomarkers to monitor treatment response and to target specific brain areas for innovative neuromodulation therapies.

Phase I trial of caudate deep brain stimulation for treatment-resistant tinnitus.

OBJECTIVE: The objective of this open-label, nonrandomized trial was to evaluate the efficacy and safety of bilateral caudate nucleus deep brain stimulation (DBS) for treatment-resistant tinnitus. METHODS: Six participants underwent DBS electrode implantation. One participant was removed from the study for suicidality unrelated to brain stimulation. Participants underwent a stimulation optimization period that ranged from 5 to 13 months, during which the most promising stimulation parameters for tinnitus reduction for each individual were determined. These individual optimal stimulation parameters were then used during 24 weeks of continuous caudate stimulation to reach the endpoint. The primary outcome for efficacy was the Tinnitus Functional Index (TFI), and executive function (EF) safety was a composite z-score from multiple neuropsychological tests (EF score). The secondary outcome for efficacy was the Tinnitus Handicap Inventory (THI); for neuropsychiatric safety it was the Frontal Systems Behavior Scale (FrSBe), and for hearing safety it was pure tone audiometry at 0.5, 1, 2, 3, 4, and 6 kHz and word recognition score (WRS). Other monitored outcomes included surgery- and device-related adverse events (AEs). Five participants provided full analyzable data sets. Primary and secondary outcomes were based on differences in measurements between baseline and endpoint. RESULTS: The treatment effect size of caudate DBS for tinnitus was assessed by TFI [mean (SE), 23.3 (12.4)] and THI [30.8 (10.4)] scores, both of which were statistically significant (Wilcoxon signed-rank test, 1-tailed; alpha = 0.05). Based on clinically significant treatment response categorical analysis, there were 3 responders determined by TFI (≥ 13-point decrease) and 4 by THI (≥ 20-point decrease) scores. Safety outcomes according to EF score, FrSBe, audiometric thresholds, and WRS showed no significant change with continuous caudate stimulation. Surgery-related and device-related AEs were expected, transient, and reversible. There was only one serious AE, a suicide attempt unrelated to caudate neuromodulation in a participant in whom stimulation was in the off mode for 2 months prior to the event. CONCLUSIONS: Bilateral caudate nucleus neuromodulation by DBS for severe, refractory tinnitus in this phase I trial showed very encouraging results. Primary and secondary outcomes revealed a highly variable treatment effect size and 60%-80% treatment response rate for clinically significant benefit, and no safety concerns. The design of a phase II trial may benefit from targeting refinement for final DBS lead placement to decrease the duration of the stimulation optimization period and to increase treatment effect size uniformity.Clinical trial registration no.: NCT01988688 (clinicaltrials.gov).

Vocal motor control and central auditory impairments in unilateral vocal fold paralysis.

OBJECTIVES: To evaluate differences in vocal motor control and central auditory processing between treated unilateral vocal fold paralysis (UVFP) and healthy control cohorts. STUDY DESIGN: Cross-sectional. METHODS: Ten UVFP study patients treated by type I thyroplasty with stable voices were compared to 12 control subjects for vocal motor control using a pitch perturbation response task and central auditory processing performance using a battery of complex sound intelligibility assays that included adverse temporal and noise conditions. Standard clinical evaluations of voice production and peripheral audiometric sensitivity were performed. RESULTS: Vocal motor control was impaired in treated UVFP. The UVFP cohort exhibited a 32.5% reduction in the instantaneous, subconscious compensatory response to pitch feedback perturbation in the interval between 150 ms and 550 ms following onset (P < 0.0001, linear mixed effects model). This impairment cannot simply be ascribed to vocal motor capacity insufficiency in the UVFP cohort because both cohorts demonstrated comparable functional capacity to perform the vocal motor task. The UVFP cohort also showed greater propensity for central auditory processing impairment (P < 0.05), notably for temporal compression and added noise challenges. CONCLUSION: Combined central vocal motor control and auditory processing impairments in treated UVFP highlight reciprocal interdependency of sensory and motor systems. This pilot study suggests that peripheral motor impairment of the larynx can degrade central auditory processing, which in turn may contribute to vocal motor control impairment. A more complete restoration communicative function in UVFP will require deeper understanding of sensory, motor, and sensorimotor aspects of the human communication loop. LEVEL OF EVIDENCE: 3b Laryngoscope, 129:2112-2117, 2019.

Human caudate nucleus subdivisions in tinnitus modulation.

OBJECTIVE: The object of this study was to define caudate nucleus locations responsive to intraoperative direct electrical stimulation for tinnitus loudness modulation and relate those locations to functional connectivity maps between caudate nucleus subdivisions and auditory cortex. METHODS: Six awake study participants who underwent bilateral deep brain stimulation (DBS) electrode placement in the caudate nucleus as part of a phase I clinical trial were analyzed for tinnitus modulation in response to acute stimulation at 20 locations. Resting-state 3-T functional MRI (fMRI) was used to compare connectivity strength between centroids of tinnitus loudness-reducing or loudness-nonreducing caudate locations and the auditory cortex in the 6 DBS phase I trial participants and 14 other neuroimaging participants with a Tinnitus Functional Index > 50. RESULTS: Acute tinnitus loudness reduction was observed at 5 caudate locations, 4 positioned at the body and 1 at the head of the caudate nucleus in normalized Montreal Neurological Institute space. The remaining 15 electrical stimulation interrogations of the caudate head failed to reduce tinnitus loudness. Compared to the caudate head, the body subdivision had stronger functional connectivity to the auditory cortex on fMRI (p < 0.05). CONCLUSIONS: Acute tinnitus loudness reduction was more readily achieved by electrical stimulation of the caudate nucleus body. Compared to the caudate head, the caudate body has stronger functional connectivity to the auditory cortex. These first-in-human findings provide insight into the functional anatomy of caudate nucleus subdivisions and may inform future target selection in a basal ganglia-centric neuromodulation approach to treat medically refractory tinnitus.Clinical trial registration no.: NCT01988688 (clinicaltrials.gov).

Cortical networks for speech motor control in unilateral vocal fold paralysis.

OBJECTIVE: To evaluate brain networks for motor control of voice production in patients with treated unilateral vocal fold paralysis (UVFP). STUDY DESIGN: Cross-sectional comparison. METHODS: Nine UVFP patients treated by type I thyroplasty, and 11 control subjects were compared using magnetoencephalographic imaging to measure beta band (12-30 Hz) neural oscillations during voice production with perturbation of pitch feedback. Differences in beta band power relative to baseline were analyzed to identify cortical areas with abnormal activity within the 400 ms perturbation period and 125 ms beyond, for a total of 525 ms. RESULTS: Whole-brain task-induced beta band activation patterns were qualitatively similar in both treated UVFP patients and healthy controls. Central vocal motor control plasticity in UVFP was expressed within constitutive components of central human communication networks identified in healthy controls. Treated UVFP patients exhibited statistically significant enhancement (P < 0.05) in beta band activity following pitch perturbation onset in left auditory cortex to 525 ms, left premotor cortex to 225 ms, and left and right frontal cortex to 525 ms. CONCLUSION: This study further corroborates that a peripheral motor impairment of the larynx can affect central cortical networks engaged in auditory feedback processing, vocal motor control, and judgment of voice-as-self. Future research to dissect functional relationships among constitutive cortical networks could reveal neurophysiological bases of central contributions to voice production impairment in UVFP. Those novel insights would motivate innovative treatments to improve voice production and reduce misalignment of voice-quality judgment between clinicians and patients. LEVEL OF EVIDENCE: 3b Laryngoscope, 129:2125-2130, 2019.

Automated smartphone audiometry: Validation of a word recognition test app.

OBJECTIVES/HYPOTHESIS: Develop and validate an automated smartphone word recognition test. STUDY DESIGN: Cross-sectional case-control diagnostic test comparison. METHODS: An automated word recognition test was developed as an app for a smartphone with earphones. English-speaking adults with recent audiograms and various levels of hearing loss were recruited from an audiology clinic and were administered the smartphone word recognition test. Word recognition scores determined by the smartphone app and the gold standard speech audiometry test performed by an audiologist were compared. RESULTS: Test scores for 37 ears were analyzed. Word recognition scores determined by the smartphone app and audiologist testing were in agreement, with 86% of the data points within a clinically acceptable margin of error and a linear correlation value between test scores of 0.89. CONCLUSIONS: The WordRec automated smartphone app accurately determines word recognition scores. LEVEL OF EVIDENCE: 3b. Laryngoscope, 128:707-712, 2018.

Abnormal Speech Motor Control in Individuals with 16p11.2 Deletions.

Speech and motor deficits are highly prevalent (>70%) in individuals with the 600 kb BP4-BP5 16p11.2 deletion; however, the mechanisms that drive these deficits are unclear, limiting our ability to target interventions and advance treatment. This study examined fundamental aspects of speech motor control in participants with the 16p11.2 deletion. To assess capacity for control of voice, we examined how accurately and quickly subjects changed the pitch of their voice within a trial to correct for a transient perturbation of the pitch of their auditory feedback. When compared to controls, 16p11.2 deletion carriers show an over-exaggerated pitch compensation response to unpredictable mid-vocalization pitch perturbations. We also examined sensorimotor adaptation of speech by assessing how subjects learned to adapt their sustained productions of formants (speech spectral peak frequencies important for vowel identity), in response to consistent changes in their auditory feedback during vowel production. Deletion carriers show reduced sensorimotor adaptation to sustained vowel identity changes in auditory feedback. These results together suggest that 16p11.2 deletion carriers have fundamental impairments in the basic mechanisms of speech motor control and these impairments may partially explain the deficits in speech and language in these individuals.

Hearing loss and tinnitus in survivors with chemotherapy-induced neuropathy.

PURPOSE: The purpose of this study was to evaluate for differences in demographic, clinical, and pain characteristics, as well as measures of sensation, balance, perceived stress, symptom burden, and quality of life (QOL) among survivors who received neurotoxic chemotherapy (CTX) and who reported only chemotherapy-induced neuropathy (CIN, n = 217), CIN and hearing loss (CIN/HL, n = 69), or CIN, hearing loss, and tinnitus (CIN/HL/TIN, n = 85). We hypothesized that as the number of neurotoxicities increased, survivors would have worse outcomes. METHODS: Survivors were recruited from throughout the San Francisco Bay area. Survivors completed self-report questionnaires for pain and other symptoms, stress and QOL. Objective measures were assessed at an in person visit. RESULTS: Compared to survivors with only CIN, survivors with all three neurotoxicities were less likely to be female and less likely to report child care responsibilities. In addition, survivors with all three neurtoxicities had higher worst pain scores, greater loss of protective sensation, and worse timed get up and go scores. These survivors reported higher state anxiety and depression and poorer QOL. For some outcomes (e.g., longer duration of CIN, self-reported balance problems), significantly worse outcomes were found for the survivors with CIN/HL and CIN/HL/TIN compared to those with only CIN. CONCLUSIONS: Our findings suggest that compared to survivors with only CIN, survivors with CIN/HL/TIN are at increased risk for the most severe symptom burden, significant problems associated with sensory loss and changes in balance, as well as significant decrements in all aspects of QOL.

Spatial plasticity of the auditory cortex in single-sided deafness.

OBJECTIVES/HYPOTHESIS: To evaluate spatial plasticity of the auditory cortex in single-sided deafness (SSD). STUDY DESIGN: Cross-sectional study comparing a cohort with adult-onset, idiopathic SSD to a cohort with normal hearing. METHODS: Demographic, audiometric, magnetoencephalographic imaging, and magnetic resonance imaging data were collected for 13 SSD adult subjects and 13 normal-hearing controls. Locations of peak activation corresponding to the M100 response in auditory cortices ipsilateral and contralateral to tonal stimuli (0.5 kHz and 4 kHz) were extracted from advanced biomagnetic source imaging analyses. Spatial extent of frequency representation across the 0.5 kHz to 4 kHz zone was computed for the two hemispheres. RESULTS: Spatial separation distance between peak locations for 0.5 kHz and 4 kHz stimuli in SSD showed increased activation spread distance in the hemisphere contralateral to the only hearing ear and decreased distance in the ipsilateral hemisphere. In contrast, normal hearing controls had nearly the same activation spread distance in the two hemispheres for ipsilateral and contralateral inputs. The difference between interhemispheric activation spread distance in SSD is significantly increased to 6.5 mm, when compared to 1.7 mm in normal controls (P < .05). CONCLUSIONS: Loss of unilateral peripheral input in SSD is associated with spatial reorganization of the auditory cortex in both hemispheres. This change in central auditory functional organization may in turn lead to higher order hearing deficits that rely on interhemispheric processing. Hearing optimization in the only hearing ear may require remediation of both spatial and temporal central auditory changes in SSD. LEVEL OF EVIDENCE: NA Laryngoscope, 126:2785-2791, 2016.