Assessment of Central Auditory Processing in Children Using a Novel Tablet-Based Platform: Application for Low- and Middle-Income Countries.

OBJECTIVE: Evaluate whether a portable, tablet-based central auditory processing (CAP) test system using native language training videos and administered by minimally trained community health workers can produce CAP results comparable to previously published norms. Our secondary aim was to determine subject parameters that influence test results. STUDY DESIGN: Cross-sectional study. SETTING: Community-based settings in Chontales, Nicaragua, New Hampshire, and Florida. PATIENTS: English- and/or Spanish-speaking children and adolescents (n = 245; average age, 12.20 yr; range, 6-18 yr). MAIN OUTCOME MEASURES: Completion of the following tests with responses comparable to published norms: Pure-tone average (PTA), gap detection threshold (GDT), fixed-level frequency threshold, masking level difference (MLD), Hearing in Noise Test (HINT), Dichotic Digits Test (DDT), and Frequency Pattern Recognition (FPR) test. RESULTS: GDT, HINT, and DDT had comparable results to previously published normative values. MLD and FPR results differed compared with previously published normative values. Most CAP tests (MLD, GDT, HINT) results were independent of age and PTA (p = 0.1-0.9). However, DDT was associated with age and PTA (p < 0.0001). CONCLUSIONS: Pediatric CAP testing can be successfully completed in remote low- and middle- income country environments using a tablet-based platform without the presence of an audiologist. Performance on DDT improved with age but deteriorated with hearing loss. Further investigation is warranted to assess the variability of FPR.

Auditory neural processing in children living with HIV uncovers underlying central nervous system dysfunction.

OBJECTIVE: Central nervous system (CNS) damage from HIV infection or treatment can lead to developmental delays and poor educational outcomes in children living with HIV (CLWH). Early markers of central nervous system dysfunction are needed to target interventions and prevent life-long disability. The frequency following response (FFR) is an auditory electrophysiology test that can reflect the health of the central nervous system. In this study, we explore whether the FFR reveals auditory central nervous system dysfunction in CLWH. STUDY DESIGN: Cross-sectional analysis of an ongoing cohort study. Data were from the child's first visit in the study. SETTING: The infectious disease center in Dar es Salaam, Tanzania. METHODS: We collected the FFR from 151 CLWH and 151 HIV-negative children. To evoke the FFR, three speech syllabi (/da/, /ba/, /ga/) were played monaurally to the child's right ear. Response measures included neural timing (peak latencies), strength of frequency encoding (fundamental frequency and first formant amplitude), encoding consistency (inter-response consistency), and encoding precision (stimulus-to-response correlation). RESULTS: CLWH showed smaller first formant amplitudes ( P  < 0.0001), weaker inter-response consistencies ( P  < 0.0001) and smaller stimulus to response correlations ( P  < 0.0001) than FFRs from HIV-negative children. These findings generalized across the three speech stimuli with moderately strong effect sizes (partial η2 ranged from 0.061 to 0.094). CONCLUSION: The FFR shows auditory central nervous system dysfunction in CLWH. Neural encoding of auditory stimuli was less robust, more variable, and less accurate. As the FFR is a passive and objective test, it may offer an effective way to assess and detect central nervous system function in CLWH.

Peripheral Auditory Function in Tanzanian Children Living With HIV With Clinically Normal Hearing.

Importance: Despite normal audiometry, adults living with HIV have lower distortion product otoacoustic emissions (DPOAEs) compared with HIV-negative controls, but the degree of these differences in children living with HIV is unknown. If subclinical auditory deficits are present, results could affect developmental outcomes in children living with HIV (CLWH). Objective: To compare DPOAEs and auditory brainstem responses (ABR) between 2 age- and sex-matched groups of younger children with normal audiometry, 1 infected with HIV and the other uninfected. Design, Setting, and Participants: Cohort study in an infectious disease center in Dar es Salaam, Tanzania. Participants included 340 Tanzanian children aged 3 to 9 years with clinically normal hearing, type A tympanograms bilaterally, and air-conduction thresholds of 20 dB HL or less from 0.5 to 8 kHz. Participants in the cohort repeated testing approximately every 6 months (approximately 2.2 sessions per participant) for a total of 744 total observations. Data were analyzed from March 2020 to January 2022. Main Outcomes and Measures: DPOAE amplitudes from 1.5 to 8 kHz using an f2 to f1 ratio of 1.2 and L1/L2 values of 65/55 dB sound pressure level and click-evoked ABR using a slow (21.1/s) and fast (61.1/s) click rate. Results: A total of 141 CLWH (70 female participants [49.3%]; mean [SD] age, 7.24 [1.67] years) and 199 HIV-negative individuals (99 female participants [49.7%]; mean [SD] age, 7.26 [1.44] years) participated in the study. The groups did not differ significantly in age, static immittance, or air-conduction thresholds. HIV status was independently associated with approximately 1.4 dB (95% CI, -3.28 to 0.30 dB) to 3.8 dB (95% CI, 6.03 to -1.99 dB) lower DPOAE amplitudes at 6 and 8 kHz bilaterally and 0.28 µV (95% CI, 0.01 to 0.33 µV) lower ABR wave V amplitudes in the right ear. Conclusions and Relevance: Consistent with previous findings in young adults, CLWH had slightly, but reliably, lower DPOAEs and ABR wave V amplitudes than HIV-negative controls. The magnitude of these differences was small, but results suggest an early and consistent association between HIV infection or treatment and outer hair cell and auditory brainstem responses in children as young as 3 years. These subclinical changes suggest tracking both auditory function and development outcomes in CLWH is warranted.

Test-Retest repeatability of automated threshold audiometry in Nicaraguan schoolchildren.

OBJECTIVE: Automated threshold audiometry (ATA) could increase access to paediatric hearing assessment in low- and middle-income countries, but few studies have evaluated test-retest repeatability of ATA in children. This study aims to analyse test-retest repeatability of ATA and to identify factors that affect the reliability of this method. DESIGN: ATA was performed twice in a cohort of Nicaraguan schoolchildren. During testing, the proportion of responses occurring in the absence of a stimulus was measured by calculating a stimulus response false positive rate (SRFP). Absolute test-retest repeatability was determined between the two trials, as well as the impact of age, gender, ambient noise, head circumference, and SRFP on these results. STUDY SAMPLE: 807 children were randomly selected from 35 schools in northern Nicaragua. RESULTS: Across all frequencies, the absolute value of the difference between measurements was 5.5 ± 7.8 dB. 89.6% of test-retest differences were within 10 dB. Intra-class correlation coefficients between the two measurements showed that lower SRFP was associated with improved repeatability. No effect of age, gender, or ambient noise was found. CONCLUSIONS: ATA produced moderate test-retest repeatability in Nicaraguan schoolchildren. Participant testing behaviours, such as delayed or otherwise inappropriate response patterns, significantly impacts the repeatability of these measurements.

Distortion product otoacoustic mapping measured pre- and post-loud sound exposures.

OBJECTIVE: Sampling distortion product otoacoustic emissions (DPOAEs) at multiple f2/f1 ratios and f2 frequency values produces a DPOAE "map." This study examined the efficacy of DPOAE mapping compared with pure tone audiometry and standard DPOAEs for detecting noise effects in subjects exposed to loud sound. DESIGN: A map significance score was developed as a single measure of map change. Significance scores were evaluated before and after exposure to: loud music (LM), controlled noise (CN), and firing range noise (FR) in three separate sets of subjects. Scores were compared to audiometry and standard DPOAE results in the LM study. STUDY SAMPLE: The LM and CN exposure studies involved 22, and 20 healthy young subjects respectively with normal hearing. Eight Marines were studied before and after FR exposure. RESULTS: After LM exposure, audiometry showed significant changes at 1, 2, 4, and 6 kHz. Standard DPOAE measures were also significantly different at several frequencies. Map significance scores detected changes more effectively and showed the distribution of DPOAE alterations. CONCLUSIONS: Map significance scores detected changes after noise exposure more reliably than audiometry and standard DPOAEs. Additionally, maps showed a diffuse response to sound exposure perhaps explaining why individual DP-grams appear less sensitive.

Peripheral Auditory Function in Young HIV-Positive Adults With Clinically Normal Hearing.

OBJECTIVE: Little is known about peripheral auditory function in young adults with HIV, who might be expected to show early evidence of hearing loss if HIV infection or treatment does affect peripheral function. The goal of this study was to compare peripheral auditory function in 2 age- and gender-matched groups of young adults with clinically normal hearing with and without HIV. STUDY DESIGN: Matched cohort study with repeated measures. SETTING: Infectious disease center in Dar es Salaam, Tanzania. METHODS: Participants included HIV-positive (n = 38) and HIV-negative (n = 38) adults aged 20 to 30 years who had clinically normal hearing, defined as type A tympanograms, air conduction thresholds ≤25 dB HL bilaterally from 0.5 to 8 kHz, and distortion product otoacoustic emissions (DPOAEs) >6 dB above the noise floor bilaterally from 1.5 to 8 kHz. Participants were tested multiple times over 6-month intervals (average, 2.7 sessions/participant) for a total of 208 observations. Primary outcome measures included tympanograms, air conduction audiograms, DPOAEs, and click-evoked auditory brainstem responses. RESULTS: HIV groups did not significantly differ in age, static immittance, or air conduction thresholds. HIV-positive status was independently associated with approximately 3.7-dB lower DPOAE amplitudes from 2 to 8 kHz (95% CI, 1.01-6.82) in both ears and 0.04-µV lower (95% CI, 0.003-0.076) auditory brainstem response wave I amplitudes in the right ear. CONCLUSION: Young adults living with HIV have slightly but reliably smaller DPOAEs and auditory brainstem response wave I amplitudes than matched HIV-negative controls. The magnitude of these differences is small, but these results support measuring peripheral auditory function in HIV-positive individuals as they age.

The Relationship Between Central Auditory Tests and Neurocognitive Domains in Adults Living With HIV.

Objective: Tests requiring central auditory processing, such as speech perception-in-noise, are simple, time efficient, and correlate with cognitive processing. These tests may be useful for tracking brain function. Doing this effectively requires information on which tests correlate with overall cognitive function and specific cognitive domains. This study evaluated the relationship between selected central auditory focused tests and cognitive domains in a cohort of normal hearing adults living with HIV and HIV- controls. The long-term aim is determining the relationships between auditory processing and neurocognitive domains and applying this to analyzing cognitive function in HIV and other neurocognitive disorders longitudinally. Method: Subjects were recruited from an ongoing study in Dar es Salaam, Tanzania. Central auditory measures included the Gap Detection Test (Gap), Hearing in Noise Test (HINT), and Triple Digit Test (TDT). Cognitive measures included variables from the Test of Variables of Attention (TOVA), Cogstate neurocognitive battery, and Kiswahili Montreal Cognitive Assessment (MoCA). The measures represented three cognitive domains: processing speed, learning, and working memory. Bootstrap resampling was used to calculate the mean and standard deviation of the proportion of variance explained by the individual central auditory tests for each cognitive measure. The association of cognitive measures with central auditory variables taking HIV status and age into account was determined using regression models. Results: Hearing in Noise Tests and TDT were significantly associated with Cogstate learning and working memory tests. Gap was not significantly associated with any cognitive measure with age in the model. TDT explained the largest mean proportion of variance and had the strongest relationship to the MoCA and Cogstate tasks. With age in the model, HIV status did not affect the relationship between central auditory tests and cognitive measures. Age was strongly associated with multiple cognitive tests. Conclusion: Central auditory tests were associated with measures of learning and working memory. Compared to the other central auditory tests, TDT was most strongly related to cognitive function. These findings expand on the association between auditory processing and cognitive domains seen in other studies and support evaluating these tests for tracking brain health in HIV and other neurocognitive disorders.

Unexplained multi-sensory neuropathy syndrome in young Tanzanian adults.

BACKGROUND: A unique syndrome affecting young adults of unexplained hearing loss often associated with uncorrectable poor visual acuity and lower extremity numbness is endemic in Dar es Salaam. This study characterized the hearing loss, associated it with other symptoms, and gathered information on potential causes. METHODS: Forty-seven patients (23 men, 24 women) <40 years old with a symptom consistent with the syndrome, negative syphilis test, and no head injury history were recruited from Muhimbili National Hospital. 18 controls (10 men, 8 women) were recruited from the same neighborhoods as patients. Hearing ability and cochlear outer hair cell function (distortion-product otoacoustic emissions (DPOAEs)) were assessed, as were visual acuity and color vision. Peripheral neuropathy was evaluated using the Michigan Neuropathy Screening Instrument (MNSI), and physical examination. Blood C-reactive protein levels and toenail trace metal concentrations were measured. Environmental exposures were elicited using a questionnaire. Patients with at least two of the following signs were defined as having the syndrome: poor hearing with normal DPOAEs, vision not correctable to better than 20/30, or a MNSI score greater than 4. RESULTS: 29 participants met the case definition. CRP levels did not differ between groups but manganese, cobalt and tin levels were each greater in the cases than controls. No other environmental exposure differences were noted. CONCLUSIONS: Toenail manganese, cobalt, and tin levels were higher in those with the syndrome. These metals are potential neurotoxins suggesting a possible environmental origin for this unique and debilitating syndrome.

Use of custom-moulded earmoulds to improve repeatability of DPOAE map measurements.

OBJECTIVE: Distortion product otoacoustic emission (DPOAE) mapping characterises cochlear function, can include both the 2f1-2f2 and 2f2-2f1 DPOAEs, and shows promise for tracking cochlear changes. DPOAE amplitude measurements are not as repeatable longitudinally as pure-tone audiometry, likely due in part to probe placement sensitivity. We hypothesised that DPOAE level map variation over multiple testing sessions could be minimised by replacing traditional rubber tips with custom-moulded probe tips. DESIGN: Traditional rubber tips (TRT) and custom-moulded probes tips (CMPT) were used to measure DPOAE level maps repeatedly over five sessions. Probe placement was assessed using a frequency sweep in the ear canal. Repeatability of the DPOAE level maps was assessed using a Bland-Altman analysis. Overall map repeatability was assessed by measuring differences in distortion product amplitude over sessions. STUDY SAMPLE: Crossover study with a convenience sample size of six adults. RESULTS: The CMPT frequency sweeps showed reduced variability in probe placement. The repeatability coefficient for individual DPOAEs measurements improved from 6.9 dB SPL with the TRT to 5.1 dB SPL with the CMPT. Map repeatability improved for most subjects with the CMPT.

Auditory neurophysiology reveals central nervous system dysfunction in HIV-infected individuals.

OBJECTIVE: To test the hypothesis that human immunodeficiency virus (HIV) affects auditory-neurophysiological functions. METHODS: A convenience sample of 68 HIV+ and 59 HIV- normal-hearing adults was selected from a study set in Dar es Salaam, Tanzania. The speech-evoked frequency-following response (FFR), an objective measure of auditory function, was collected. Outcome measures were FFRs to the fundamental frequency (F0) and to harmonics corresponding to the first formant (F1), two behaviorally relevant cues for understanding speech. RESULTS: The HIV+ group had weaker responses to the F1 than the HIV- group; this effect generalized across multiple stimuli (d = 0.59). Responses to the F0 were similar between groups. CONCLUSIONS: Auditory-neurophysiological responses differ between HIV+ and HIV- adults despite normal hearing thresholds. SIGNIFICANCE: The FFR may reflect HIV-associated central nervous system dysfunction that manifests as disrupted auditory processing of speech harmonics corresponding to the first formant.

Reliability of Tablet-based Hearing Testing in Nicaraguan Schoolchildren: A Detailed Analysis.

OBJECTIVE: Determine whether an electronic tablet-based Wireless Automated Hearing-Test System can perform high-quality audiometry to assess schoolchildren for hearing loss in the field in Nicaragua. STUDY DESIGN: Cross-sectional. SETTING: A school and hospital-based audiology clinic in Jinotega, Nicaragua. SUBJECTS AND METHODS: Second and third graders (n = 120) were randomly selected for hearing testing in a school. Air conduction hearing thresholds were obtained bilaterally using a Wireless Automated Hearing-Test System at 1000, 2000, and 4000 Hz. Referral criteria were set at more than 25 dBHL at one or more frequencies. A cohort of children was retested with conventional audiometry in a hospital-based sound booth. Factors influencing false-positive examinations, including ambient noise and behavior, were examined. RESULTS: All children with hearing loss were detected using an automated, manual, or two-step (those referred from automated testing were tested manually) protocol in the school (sensitivity = 100%). Specificity was 76% for automated testing, 97% for manual testing, and 99% for the two-step protocol. The variability between thresholds obtained with automated testing was greater than manual testing when compared with conventional audiometry. The percentage of participant responses when no stimulus tone was presented during automated testing was higher in children with false-positive examinations. CONCLUSION: A Wireless Automated Hearing-Test System identified all children with hearing loss in a challenging field setting. A two-step protocol (those referred from automated testing are tested manually) reduced false-positive examinations and unnecessary referrals. Children who respond frequently when no tone is presented are more likely to have false-positive automated examinations and should be tested manually.

Fixed-Level Frequency Threshold Testing for Ototoxicity Monitoring.

OBJECTIVES: Hearing loss from ototoxicity is often most pronounced at high frequencies. To improve patient monitoring and compliance, high-frequency testing methods should be short and easy to administer. We evaluated the repeatability and accuracy of a Békésy-like, fixed-level frequency threshold (FLFT) technique. This test takes less than a minute and could provide a rapid and effective way to determine the highest audible frequency. We hypothesized the FLFT test would be repeatable in normal-hearing subjects, and accurate when compared with Békésy fixed-frequency audiometry in the sensitive region for ototoxicity (SRO). DESIGN: Twenty-nine normal-hearing subjects (20 females, 9 males) performed 2 different automated audiometry tests at least 4 times over a period of no less than 3 weeks. Ages ranged from 23 to 35 years (average = 28 years). Subjects completed testing under Sennheiser HDA-200 headsets. Initial fixed-frequency audiometry thresholds were obtained at frequencies ranging from 0.5 to 20 kHz to identify each subject's highest audible frequency, which was used to determine the SRO. The SRO was defined as the seven frequencies at and below the highest audible frequency in 1/6-octave steps. These frequencies were monitored with fixed-frequency audiometry. At each session, the FLFT test was administered at 80 dB SPL. Subjects used a Békésy-style tracking method to determine the frequency threshold. All testing was completed in a sound booth (single wall, Industrial Acoustics Company) using a computerized, laptop-based, system. FLFT repeatability was calculated as the root mean square difference from the first test session. FLFT accuracy was calculated as the difference from the highest audible frequency determined from fixed-frequency audiometry interpolated to 80 dB SPL level. RESULTS: The FLFT average RMSD for intersession variability was 0.05 ± 0.05 octaves. The test showed no learning effect [F(3,78) = 0.7; p = 0.6]. The overall intersession variability for SRO fixed-frequency audiometry thresholds at all frequencies was within clinically acceptable test-retest variability (10 dB) at 5.8 dB (range 2.7 to 9.9 dB). The SRO fixed-frequency audiometry therefore served as a repeatable basis of comparison for accuracy of the FLFT test. The mean absolute difference between the fixed-frequency audiometry and FLFT-determined highest audible frequency was 0.03 octaves. The FLFT and the highest audible frequency via fixed-frequency audiometry at 80 dB SPL were not different statistically (p = 0.12). The FLFT took approximately 30 seconds to complete, compared with approximately 4.5 min for fixed-frequency audiometry SRO and 20 to 25 min for a traditional ototoxic audiometric assessment. CONCLUSIONS: The Békésy-style FLFT was repeatable within 1/12 octave (1 step size in the testing procedure). The FLFT agreed well with the highest audible frequency determined via fixed-frequency audiometry at 80 dB SPL. The FLFT test is amenable to automatic and self-administration and may enable quick, accurate, noise-tolerant ototoxicity, and high-frequency hearing monitoring.

Auditory Impairments in HIV-Infected Children.

OBJECTIVES: In a cross-sectional study of human immunodeficiency virus (HIV)-infected adults, the authors showed lower distortion product otoacoustic emissions (DPOAEs) in HIV+ individuals compared with controls as well as findings consistent with a central auditory processing deficit in HIV+ adults on antiretroviral therapy. The authors hypothesized that HIV+ children would also have a higher prevalence of abnormal central and peripheral hearing test results compared with HIV- controls. DESIGN: Pure-tone thresholds, DPOAEs, and tympanometry were performed on 244 subjects (131 HIV+ and 113 HIV- subjects). Thirty-five of the HIV+, and 3 of the HIV- subjects had a history of tuberculosis treatment. Gap detection results were available for 18 HIV- and 44 HIV+ children. Auditory brainstem response results were available for 72 HIV- and 72 HIV+ children. Data from ears with abnormal tympanograms were excluded. RESULTS: HIV+ subjects were significantly more likely to have abnormal tympanograms, histories of ear drainage, tuberculosis, or dizziness. All audiometric results were compared between groups using a two-way ANOVA with HIV status and ear drainage history as grouping variables. Mean audiometric thresholds, gap detection thresholds, and auditory brainstem response latencies did not differ between groups, although the HIV+ group had a higher proportion of individuals with a hearing loss >25 dB HL in the better ear. The HIV+ group had reduced DPOAE levels (p < 0.05) at multiple frequencies compared with HIV- subjects. No relationships were found between treatment regimens or delay in starting treatment and audiological parameters. CONCLUSIONS: As expected, children with HIV+ were more likely to have a history of ear drainage, and to have abnormal tympanograms. Similar to the adult findings, the HIV+ group did not show significantly reduced audiometric thresholds, but did have significantly lower DPOAE magnitudes. These data suggest that (1) HIV+ children often have middle ear damage which complicates understanding the direct effects of HIV on the hearing system, and (2) even when corrected for confounders DPOAEs were lower in the HIV+ group. Previous studies suggest ototoxicity from antiretroviral drugs is an unlikely cause of the reduced DPOAE magnitudes. Other possibilities include effects on efferent pathways connecting to outer hair cells or a direct effect of HIV on the cochlea.