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.

Multiple Cases of Auditory Neuropathy Illuminate the Importance of Subcortical Neural Synchrony for Speech-in-noise Recognition and the Frequency-following Response.

OBJECTIVES: The role of subcortical synchrony in speech-in-noise (SIN) recognition and the frequency-following response (FFR) was examined in multiple listeners with auditory neuropathy. Although an absent FFR has been documented in one listener with idiopathic neuropathy who has severe difficulty recognizing SIN, several etiologies cause the neuropathy phenotype. Consequently, it is necessary to replicate absent FFRs and concomitant SIN difficulties in patients with multiple sources and clinical presentations of neuropathy to elucidate fully the importance of subcortical neural synchrony for the FFR and SIN recognition. DESIGN: Case series. Three children with auditory neuropathy (two males with neuropathy attributed to hyperbilirubinemia, one female with a rare missense mutation in the OPA1 gene) were compared to age-matched controls with normal hearing (52 for electrophysiology and 48 for speech recognition testing). Tests included standard audiological evaluations, FFRs, and sentence recognition in noise. The three children with neuropathy had a range of clinical presentations, including moderate sensorineural hearing loss, use of a cochlear implant, and a rapid progressive hearing loss. RESULTS: Children with neuropathy generally had good speech recognition in quiet but substantial difficulties in noise. These SIN difficulties were somewhat mitigated by a clear speaking style and presenting words in a high semantic context. In the children with neuropathy, FFRs were absent from all tested stimuli. In contrast, age-matched controls had reliable FFRs. CONCLUSION: Subcortical synchrony is subject to multiple forms of disruption but results in a consistent phenotype of an absent FFR and substantial difficulties recognizing SIN. These results support the hypothesis that subcortical synchrony is necessary for the FFR. Thus, in healthy listeners, the FFR may reflect subcortical neural processes important for SIN recognition.

Nonverbal cognitive assessment of children in Tanzania with and without HIV.

Children living with HIV can experience cognitive difficulties. Most neuropsychological tests have been constructed in Western languages, meaning they may not be appropriate for use in non-Western settings. To address this, we used an entirely nonverbal measure of cognitive ability in a sub-Saharan African sample. For this cross-sectional analysis, 316 children (162 HIV+ and 154 HIV-, ages 3-9) completed the Leiter-3 as part of a larger study in Dar es Salaam, Tanzania. Statistical tests included analysis of covariance and multiple linear regression to account for environmental variables. HIV+ children performed worse than HIV - controls on two composite scores: Nonverbal IQ (p < .001) and Processing Speed (p < 0.001). Similar trends were observed on core subtests. Multiple linear regression models revealed that age, socioeconomic status, and school attendance predicted all Leiter-3 test composites. Critically, the addition of HIV status to the models improved prediction of Nonverbal IQ (∆R2 = 0.03, p = .001) and Processing Speed (∆R2 = 0.06, p < .001). Children living with HIV performed worse than HIV- controls on most Leiter-3 measures. While age, SES, and school attendance predicted Leiter-3 performance, HIV status improved prediction capabilities when added to the model. The Leiter-3 may offer a viable measure of cognitive ability in non-Western settings that can be used in its original form without translation.

Auditory neurophysiological development in early childhood: A growth curve modeling approach.

OBJECTIVE: During early childhood, the development of communication skills, such as language and speech perception, relies in part on auditory system maturation. Because auditory behavioral tests engage cognition, mapping auditory maturation in the absence of cognitive influence remains a challenge. Furthermore, longitudinal investigations that capture auditory maturation within and between individuals in this age group are scarce. The goal of this study is to longitudinally measure auditory system maturation in early childhood using an objective approach. METHODS: We collected frequency-following responses (FFR) to speech in 175 children, ages 3-8 years, annually for up to five years. The FFR is an objective measure of sound encoding that predominantly reflects auditory midbrain activity. Eliciting FFRs to speech provides rich details of various aspects of sound processing, namely, neural timing, spectral coding, and response stability. We used growth curve modeling to answer three questions: 1) does sound encoding change across childhood? 2) are there individual differences in sound encoding? and 3) are there individual differences in the development of sound encoding? RESULTS: Subcortical auditory maturation develops linearly from 3-8 years. With age, FFRs became faster, more robust, and more consistent. Individual differences were evident in each aspect of sound processing, while individual differences in rates of change were observed for spectral coding alone. CONCLUSIONS: By using an objective measure and a longitudinal approach, these results suggest subcortical auditory development continues throughout childhood, and that different facets of auditory processing follow distinct developmental trajectories. SIGNIFICANCE: The present findings improve our understanding of auditory system development in typically-developing children, opening the door for future investigations of disordered sound processing in clinical populations.

Rhythm, reading, and sound processing in the brain in preschool children.

A child's success in school relies on their ability to quickly grasp language and reading skills, the foundations of which are acquired even before entering a formal classroom setting. Previous studies in preschoolers have begun to establish relationships linking beat synchronization, preliteracy skills, and auditory processing. Beat synchronization involves the integration of sensorimotor systems with auditory and cognitive circuits and, therefore calls on many of the same neural networks as language. Using a drumming task, we analyzed the relationship between children's ability to maintain an isochronous beat with preliteracy skills and frequency following responses (FFRs) in over 150 preschoolers. We show that preschoolers who performed well on the beat synchronization task outscored their peers on all preliteracy measures and had more robust FFRs. Furthermore, the good synchronizers experienced less degradation of certain FFR measures when listening in noise. Together, our results are consistent with the view that rhythm, preliteracy, and auditory processing are interconnected during early childhood.

Clapping in Time With Feedback Relates Pervasively With Other Rhythmic Skills of Adolescents and Young Adults.

Rhythmic expertise is a multidimensional skill set with clusters of distinct rhythmic abilities. For example, the ability to clap in time with feedback relates extensively to distinct beat- and pattern-based rhythmic skills in school-age children. In this study we aimed to determine whether clapping in time would relate to both beat- and pattern- based rhythmic tasks among adolescents and young adults. We assessed our participants on seven tasks: two beat-based tasks (Metronome and Tempo adaptation), two pattern-based tasks (Reproducing rhythmic patterns and Remembering rhythmic patterns), a self-paced drumming task, a task of drumming to a music beat, and a clapping in time task. We found that clapping in time correlated with all other rhythmic tasks, even though some were not mutually related to one another. These results provide insight into the taxonomy of rhythmic skills and support the practice of clapping in time with feedback as a means of developing broad spectrum rhythmic abilities.

Central Auditory Tests to Track Cognitive Function in People With HIV: Longitudinal Cohort Study.

BACKGROUND: The development of neurocognitive deficits in people infected with HIV is a significant public health problem. Previous cross-sectional studies have shown that performance on central auditory tests (CATs) correlates with cognitive test results in those with HIV, but no longitudinal data exist for confirmation. We have been performing longitudinal assessments of central auditory and cognitive function on a cohort of HIV-positive and HIV-negative individuals in Dar es Salaam, Tanzania to understand how the central auditory system could be used to study and track the progress of central nervous system dysfunction. OBJECTIVE: The goal of the project was to determine if CATs can track the trajectory of cognitive function over time in people diagnosed with HIV. METHODS: Tests of peripheral and central auditory function as well as cognitive performance were performed on 382 individuals over the course of 3.5 years. Visits were scheduled every 6 months. CATs included tests of auditory temporal processing (gap detection) and speech perception in noise (Hearing in Noise Test and Triple Digit Test). Cognitive tests included the Montreal Cognitive Assessment (MoCA), Test of Variables of Attention (TOVA), and subtests from the Cogstate battery. HIV-positive subjects were divided into groups based on their CAT results at their final visit (bottom 20%, top 20%, middle 60%). Primary analyses focused on the comparison between HIV-positive individuals that performed worse on CATs (bottom 20%) and the overall HIV-positive group (middle 60%). Data were analyzed using linear mixed-effect models with time as the main fixed effect. RESULTS: The group with the worst (bottom 20%) CAT performance showed a difference in trajectory for the MoCA (P=.003), TOVA (P<.048), and Cogstate (P<.046) over the course of the study period compared to the overall HIV-positive group. A battery of three CATs showed a significant difference in cognitive trajectory over a relatively short study period of 3.5 years independent of age (bottom 20% vs HIV-positive group). CONCLUSIONS: The results of this study support the ability for CATs to track cognitive function over time, suggesting that central auditory processing can provide a window into central nervous system performance. CATs can be simple to perform, and are relatively insensitive to education and socioeconomic status because they only require repeating sentences, numbers, or detecting gaps in noise. These tests could potentially provide a time-efficient, low-cost method to screen for and monitor cognitive decline in patients with HIV, making them a useful surveillance tool for this major public health problem.

Case studies in neuroscience: cortical contributions to the frequency-following response depend on subcortical synchrony.

Frequency-following responses to musical notes spanning the octave 65-130 Hz were elicited in a person with auditory neuropathy, a disorder of subcortical neural synchrony, and a control subject. No phaselocked responses were observed in the person with auditory neuropathy. The control subject had robust responses synchronized to the fundamental frequency and its harmonics. Cortical onset responses to each note in the series were present in both subjects. These results support the hypothesis that subcortical neural synchrony is necessary to generate the frequency-following response-including for stimulus frequencies at which a cortical contribution has been noted. Although auditory cortex ensembles may synchronize to fundamental frequency cues in speech and music, subcortical neural synchrony appears to be a necessary antecedent.NEW & NOTEWORTHY A listener with auditory neuropathy, an absence of subcortical neural synchrony, did not have electrophysiological frequency-following responses synchronized to an octave of musical notes, with fundamental frequencies ranging from 65 to 130 Hz. A control subject had robust responses that phaselocked to each note. Although auditory cortex may contribute to the scalp-recorded frequency-following response in healthy listeners, our results suggest this phenomenon depends on subcortical neural synchrony.

Distinct rhythmic abilities align with phonological awareness and rapid naming in school-age children.

Difficulty in performing rhythmic tasks often co-occurs with literacy difficulties. Motivated by evidence showing that people can vary in their performance across different rhythmic tasks, we asked whether two rhythmic skills identified as distinct in school-age children and young adults would reveal similar or different relationships with two literacy skills known to be important for successful reading development. We addressed our question by focusing on 55 typically developing children (ages 5-8). Results show that drumming to a beat predicted the variability of rapid naming but not of phonological awareness, whereas tapping rhythmic patterns predicted phonological awareness, but not rapid naming. Our finding suggests that rhythmic interventions can be tailored to address PA and RAN deficits specifically in reading disabled children.

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.

Baseline profiles of auditory, vestibular, and visual functions in youth tackle football players.

AIM: Neurosensory tests have emerged as components of sport-related concussion management. Limited normative data are available in healthy, nonconcussed youth athletes. PATIENTS & METHODS/RESULTS: In 2017 and 2018, we tested 108 youth tackle football players immediately before their seasons on the frequency-following response, Balance Error Scoring System, and King-Devick test. We compared results with published data in older and/or and nonathlete populations. Performance on all tests improved with age. Frequency-following response and Balance Error Scoring System results aligned with socioeconomic status. Performance was not correlated across neurosensory domains. CONCLUSION: Baseline neurosensory functions in seven 14-year-old male tackle football players are consistent with previously published data. Results reinforce the need for individual baselines or demographic-specific norms and the use of multiple neurosensory measures in sport-related concussion management.

Performance on auditory, vestibular, and visual tests is stable across two seasons of youth tackle football.

Objective: Few studies have tracked neurologic function in youth football players longitudinally. This study aimed to determine whether changes in tests of auditory, vestibular, and/or visual functions are evident after participation in one or two seasons of youth tackle football.Study Design: Prospective cohort study.Subjects and Methods: Before their 2017 and/or 2018 seasons, male tackle football players (ages 7-14 yrs) completed three tests that tend to exhibit acute disruptions following a concussion: (1) the FFR (frequency-following response), aphysiologic test of auditory function, (2) the BESS (Balance Error Scoring System), a test of vestibular function, and (3) the King-Devick, a test of oculomotor function. We planned to repeat these on all subjects at the end of each season.Results: Performance on neurosensory tests was stable, with no changes observed in FFR or King-Devick and a slight improvement observed in BESS performance across each season. Performance was also stable over two years for the subjects who participated both years. Across-season test-retest reliability correlations were high.Conclusions: In the absence of concussion, young athletes' performance on the FFR, King-Devick, and BESS is stable across one or two seasons of youth tackle football.

Play Sports for a Quieter Brain: Evidence From Division I Collegiate Athletes.

BACKGROUND: Playing sports has many benefits, including boosting physical, cardiovascular, and mental fitness. We tested whether athletic benefits extend to sensory processing-specifically auditory processing-as measured by the frequency-following response (FFR), a scalp-recorded electrophysiological potential that captures neural activity predominately from the auditory midbrain to complex sounds. HYPOTHESIS: Given that FFR amplitude is sensitive to experience, with enrichment enhancing FFRs and injury reducing them, we hypothesized that playing sports is a form of enrichment that results in greater FFR amplitude. STUDY DESIGN: Cross-sectional study. LEVEL OF EVIDENCE: Level 3. METHODS: We measured FFRs to the speech syllable "da" in 495 student-athletes across 19 Division I teams and 493 age- and sex-matched controls and compared them on 3 measures of FFR amplitude: amplitude of the response, amplitude of the background noise, and the ratio of these 2 measures. RESULTS: Athletes have larger responses to sound than nonathletes, driven by a reduction in their level of background neural noise. CONCLUSION: These findings suggest that playing sports increases the gain of an auditory signal by turning down the background noise. This mode of enhancement may be tied to the overall fitness level of athletes and/or the heightened need of an athlete to engage with and respond to auditory stimuli during competition. CLINICAL RELEVANCE: These results motivate athletics overall and engagement in athletic interventions for populations that struggle with sensory processing, such as individuals with language disorders. Also, because head injuries can disrupt these same auditory processes, it is important to consider how auditory processing enhancements may offset injury.

Evolving perspectives on the sources of the frequency-following response.

The auditory frequency-following response (FFR) is a non-invasive index of the fidelity of sound encoding in the brain, and is used to study the integrity, plasticity, and behavioral relevance of the neural encoding of sound. In this Perspective, we review recent evidence suggesting that, in humans, the FFR arises from multiple cortical and subcortical sources, not just subcortically as previously believed, and we illustrate how the FFR to complex sounds can enhance the wider field of auditory neuroscience. Far from being of use only to study basic auditory processes, the FFR is an uncommonly multifaceted response yielding a wealth of information, with much yet to be tapped.

Neurophysiological, linguistic, and cognitive predictors of children's ability to perceive speech in noise.

Hearing in noisy environments is a complicated task that engages attention, memory, linguistic knowledge, and precise auditory-neurophysiological processing of sound. Accumulating evidence in school-aged children and adults suggests these mechanisms vary with the task's demands. For instance, co-located speech and noise demands a large cognitive load and recruits working memory, while spatially separating speech and noise diminishes this load and draws on alternative skills. Past research has focused on one or two mechanisms underlying speech-in-noise perception in isolation; few studies have considered multiple factors in tandem, or how they interact during critical developmental years. This project sought to test complementary hypotheses involving neurophysiological, cognitive, and linguistic processes supporting speech-in-noise perception in young children under different masking conditions (co-located, spatially separated). Structural equation modeling was used to identify latent constructs and examine their contributions as predictors. Results reveal cognitive and language skills operate as a single factor supporting speech-in-noise perception under different masking conditions. While neural coding of the F0 supports perception in both co-located and spatially separated conditions, neural timing predicts perception of spatially separated listening exclusively. Together, these results suggest co-located and spatially separated speech-in-noise perception draw on similar cognitive/linguistic skills, but distinct neural factors, in early childhood.

Stable auditory processing underlies phonological awareness in typically developing preschoolers.

Sound processing is an important scaffold for early language acquisition. Here we investigate its relationship to three components of phonological processing in young children (∼age 3): Phonological Awareness (PA), Phonological Memory (PM), and Rapid Automatized Naming (RAN). While PA is believed to hinge upon consistency of sound processing to distinguish and manipulate word features, PM relies on an internal store of the sounds of language and RAN relies on fluid production of those sounds. Given the previously demonstrated link between PA and the auditory system, we hypothesized that only this component would be associated with auditory neural stability. Moreover, we expected relationships to manifest at early ages because additional factors may temper the association in older children. We measured across-trial stability of the frequency-following response, PA, PM, and RAN longitudinally in twenty-seven children. Auditory neural stability at age ∼3 years exclusively predicts PA, but this relationship vanishes in older children.

Case studies in neuroscience: subcortical origins of the frequency-following response.

The auditory frequency-following response (FFR) reflects synchronized and phase-locked activity along the auditory pathway in response to sound. Although FFRs were historically thought to reflect subcortical activity, recent evidence suggests an auditory cortex contribution as well. Here we present electrophysiological evidence for the FFR's origins from two cases: a patient with bilateral auditory cortex lesions and a patient with auditory neuropathy, a condition of subcortical origin. The patient with auditory cortex lesions had robust and replicable FFRs, but no cortical responses. In contrast, the patient with auditory neuropathy had no FFR despite robust and replicable cortical responses. This double dissociation shows that subcortical synchrony is necessary and sufficient to generate an FFR.NEW & NOTEWORTHY The frequency-following response (FFR) reflects synchronized and phase-locked neural activity in response to sound.  The authors present a dual case study, comparing FFRs and cortical potentials between a patient with auditory neuropathy (a condition of subcortical origin) and a patient with bilateral auditory cortex lesions. They show that subcortical synchrony is necessary and sufficient to generate an FFR.

How Rhythmic Skills Relate and Develop in School-Age Children.

Rhythmic expertise can be considered a multidimensional skill set, with clusters of distinct rhythmic abilities evident in young adults. In this article, we explore relationships in school-age children (ages 5-8 years) among 4 rhythmic tasks hypothesized to reflect different clusters of skills, namely, drumming to an isochronous beat, remembering rhythmic patterns, drumming to the beat in music, and clapping in time with feedback. We find that drumming to an isochronous beat and remembering rhythmic patterns are not related. In addition, clapping in time with feedback correlates with performance on the other 3 rhythm tasks. This study contributes to the taxonomy of rhythmic skills in school-age children. It also supports the use of clapping in time training as a way to possibly affect a broad spectrum of rhythmic abilities that are linked to language and literacy processes.

Clapping in time parallels literacy and calls upon overlapping neural mechanisms in early readers.

The auditory system is extremely precise in processing the temporal information of perceptual events and using these cues to coordinate action. Synchronizing movement to a steady beat relies on this bidirectional connection between sensory and motor systems, and activates many of the auditory and cognitive processes used when reading. Here, we use Interactive Metronome, a clinical intervention technology requiring an individual to clap her hands in time with a steady beat, to investigate whether the links between literacy and synchronization skills, previously established in older children, are also evident in children who are learning to read. We tested 64 typically developing children (ages 5-7 years) on their synchronization abilities, neurophysiological responses to speech in noise, and literacy skills. We found that children who have lower variability in synchronizing have higher phase consistency, higher stability, and more accurate envelope encoding-all neurophysiological response components linked to language skills. Moreover, performing the same task with visual feedback reveals links with literacy skills, notably processing speed, phonological processing, word reading, spelling, morphology, and syntax. These results suggest that rhythm skills and literacy call on overlapping neural mechanisms, supporting the idea that rhythm training may boost literacy in part by engaging sensory-motor systems.