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.

Subconcussion revealed by sound processing in the brain.

Introduction/Purpose: We tested the hypothesis that an objective measure of auditory processing reveals a history of head trauma that does not meet the clinical definition of concussion. Methods: Division I collegiate student-athletes (n = 709) across 19 sports were divided into groups, based on their sport, using prevailing classifications of "contact" (317 males, 212 females) and "noncontact" (58 males, 122 females). Participants were evaluated using the frequency-following response (FFR) to speech. The amplitude of FFR activity in a frequency band corresponding to the fundamental frequency (F0)-the voice pitch-of the speech stimulus, an outcome reduced in individuals with concussions, was critically examined. Results: We found main effects of contact level and sex. The FFR-F0 was smaller in contact athletes than noncontact athletes and larger in females than males. There was a contact by sex interaction, with the FFR-F0 of males in the contact group being smaller than the three other groups. Secondary analyses found a correlation between FFR-F0 and length of participation in contact sports in male athletes. Conclusion: These findings suggest that the disruption of sensory processing in the brain can be observed in individuals without a concussion but whose sport features regular physical contact. This evidence identifies sound processing in the brain as an objective marker of subconcussion in athletes.

Preliteracy assessment in children living with HIV in Tanzania: comparison to results from children living without HIV in Tanzania and the United States.

OBJECTIVE: Children with HIV (CWH) are at increased risk for cognitive and developmental delays. Whether HIV affects literacy development, however, remains unknown. Rapid automatized naming (RAN) tasks offer the simplest preliteracy assessment a child can perform that predicts future reading skills across languages. DESIGN AND METHODS: RAN performance was analyzed cross-sectionally on 473 children (249 children without HIV and 217 CWH; ages 3-9) drawn from a longitudinal study in Tanzania. These data were compared to results from 341 normally developing children without HIV (ages 3-8) from the United States. Participants performed two RAN subtests: colors and objects. RESULTS: RAN object completion was greater than for the RAN color in Tanzanian children. CWH were less likely to complete either subtest and performed worse on the object subtest compared to Tanzanian children without HIV. Compared to the US cohort, the Tanzanian cohort was less likely to complete both subtests - in particular the colors subtest - and showed more variability in responses at younger ages. After approximately age 6, however, the trajectory of improvement between the United States and Tanzania was similar. CONCLUSIONS: CWH performed worse on this per-literacy test, indicating literacy skill development in CWH needs further study. The differences between US and Tanzanian results likely reflect variability in when children learn to name colors and objects. The trajectory of improvement between countries became more similar as the children aged. This study motivates further longitudinal analyses aimed at assessing the developmental trajectory of the RAN, its predictive ability for reading skills, and its link with other preliteracy and cognitive skills.

Athleticism and sex impact neural processing of sound.

Biology and experience both influence the auditory brain. Sex is one biological factor with pervasive effects on auditory processing. Females process sounds faster and more robustly than males. These differences are linked to hormone differences between the sexes. Athleticism is an experiential factor known to reduce ongoing neural noise, but whether it influences how sounds are processed by the brain is unknown. Furthermore, it is unknown whether sports participation influences auditory processing differently in males and females, given the well-documented sex differences in auditory processing seen in the general population. We hypothesized that athleticism enhances auditory processing and that these enhancements are greater in females. To test these hypotheses, we measured auditory processing in collegiate Division I male and female student-athletes and their non-athlete peers (total n = 1012) using the frequency-following response (FFR). The FFR is a neurophysiological response to sound that reflects the processing of discrete sound features. We measured across-trial consistency of the response in addition to fundamental frequency (F0) and harmonic encoding. We found that athletes had enhanced encoding of the harmonics, which was greatest in the female athletes, and that athletes had more consistent responses than non-athletes. In contrast, F0 encoding was reduced in athletes. The harmonic-encoding advantage in female athletes aligns with previous work linking harmonic encoding strength to female hormone levels and studies showing estrogen as mediating athlete sex differences in other sensory domains. Lastly, persistent deficits in auditory processing from previous concussive and repetitive subconcussive head trauma may underlie the reduced F0 encoding in athletes, as poor F0 encoding is a hallmark of concussion injury.

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.

Non-stimulus-evoked activity as a measure of neural noise in the frequency-following response.

BACKGROUND: The frequency-following response, or FFR, is a neurophysiologic response that captures distinct aspects of sound processing. Like all evoked responses, FFR is susceptible to electric and myogenic noise contamination during collection. Click-evoked auditory brainstem response collection standards have been adopted for FFR collection, however, whether these standards sufficiently limit FFR noise contamination is unknown. Thus, a critical question remains: to what extent do distinct FFR components reflect noise contamination? This is especially relevant for prestimulus amplitude (i.e., activity preceding the evoked response), as this measure has been used to index both noise contamination and neural noise. NEW METHOD: We performed two experiments. First, using >1000 young-adult FFRs, we ran regressions to determine the variance explained by myogenic and electrical noise, as indexed by artifact rejection count and electrode impedance, on each FFR component. Second, we reanalyzed prestimulus amplitude differences attributed to athletic experience and socioeconomic status, adding covariates of artifact rejection and impedance. RESULTS: We found that non-neural noise marginally contributed to FFR components and could not explain group differences on prestimulus amplitude. COMPARISON WITH EXISTING METHOD: Prestimulus amplitude has been considered a measure of non-neural noise contamination. However, non-neural noise was not the sole contributor to variance in this measure and did not explain group differences. CONCLUSIONS: Results from the two experiments suggest that the effects of non-neural noise on FFR components are minimal and do not obscure individual differences in the FFR and that prestimulus amplitude indexes neural noise.

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.

Sex differences in subcortical auditory processing only partially explain higher prevalence of language disorders in males.

Males and females differ in their subcortical evoked responses to sound. For many evoked response measures, the sex difference is driven by a faster developmental decline of auditory processing in males. Using the frequency-following response (FFR), an evoked potential that reflects predominately midbrain processing of stimulus features, sex differences were identified in the response to the temporal envelope of speech. The pattern of later and smaller responses in males versus females is consistent with two of the three response features that track with language development and reading abilities. Therefore, here we analyzed subcortical response consistency, the third distinguishing feature of language ability. Furthermore, though the envelope is primarily a low-frequency response, the greatest sex differences were observed in harmonics encoding. To better understand these sex differences, we extended these findings to the temporal fine structure response, which is biased to high-frequency information. Using the same 516 participants as previously reported (Krizman et al., 2019), we analyzed the effect of sex across development on response consistency and the encoding of temporal fine structure, as indexed by the subtracted frequency-following response. We found that while males and females did not differ on response consistency, there was an effect of age on this measure. Moreover, while males still showed a faster decline in harmonic encoding, the magnitude and breadth of the sex differences were smaller (accounting for 2% variance) in the temporal fine structure response compared to the envelope response. These results suggest that sex differences are distinct, at least in part, from the differences that underlie language abilities and that developmental sex differences reflect subcortical auditory processing differences of both the temporal envelope and fine structure of sounds.

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.

The Effectiveness of Interventions for Developmental Dyslexia: Rhythmic Reading Training Compared With Hemisphere-Specific Stimulation and Action Video Games.

Developmental dyslexia is a very common learning disorder causing an impairment in reading ability. Although the core deficit underlying dyslexia is still under debate, significant agreement is reached in the literature that dyslexia is related to a specific deficit in the phonological representation of speech sounds. Many studies also reported an association between reading skills and music. These findings suggest that interventions aimed at enhancing basic auditory skills of children with DD may impact reading abilities. However, music education alone failed to produce improvements in reading skills comparable to those resulting from traditional intervention methods for DD. Therefore, a computer-assisted intervention method, called Rhythmic Reading Training (RRT), which combines sublexical reading exercises with rhythm processing, was implemented. The purpose of the present study was to compare the effectiveness of RRT and that of an intervention resulting from the combination of two yet validated treatments for dyslexia, namely, Bakker's Visual Hemisphere-Specific Stimulation (VHSS) and the Action Video Game Training (AVG). Both interventions, administered for 13 h over 9 days, significantly improved reading speed and accuracy of a group of Italian students with dyslexia aged 8-14. However, each intervention program produced improvements that were more evident in specific reading parameters: RRT was more effective for improvement of pseudoword reading speed, whereas VHSS + AVG was more effective in increasing general reading accuracy. Such different effects were found to be associated with different cognitive mechanisms, namely, phonological awareness for RRT and rapid automatized naming for VHSS + AVG, thus explaining the specific contribution of each training approach. Clinical Trial registration: ClinicalTrials.gov NCT02791841.

Auditory Processing Differences in Toddlers With Autism Spectrum Disorder.

Purpose Auditory processing measures have been used in an attempt to understand the relationship between neurological mechanisms and autism spectrum disorder (ASD) symptomatology in school-age children. The focus of the current study was to understand neural auditory processing in 2- to 3-year-olds with ASD. Method Auditory processing measures (click auditory brainstem responses and speech-evoked frequency-following responses) were hypothesized to differ between typically developing children (n = 18) and children with ASD (n = 18). Auditory processing measures were hypothesized to relate to language development in children with ASD. Results The current study found limited differences in auditory processing measures between the two groups. No relationships were found between auditory processing measures and language development measures. Conclusions Future research is necessary to characterize auditory processing in toddlers with ASD. Longitudinal approaches should be considered when studying auditory processing in children with ASD in order to explore its developmental relationship with ASD symptomatology.

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.

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.

Sex differences in subcortical auditory processing emerge across development.

Human subcortical auditory processing is sexually dimorphic. The prevailing view - that sex differences arise from cochlear differences - remains unproven, and the extent to which these differences reflect distinct auditory processes is unknown. To determine the origin of subcortical sex differences, we mapped their emergence onto the peripheral-to-central maturation of the auditory system in 516 participants (250 female) across three age groups: 3-5, 14-15, and 22-26 years. To examine whether these sex differences arise from distinct processes, we compared developmental trajectories of each evoked-response component and tested their ability to predict a participant's sex and age. We find that some subcortical sex differences emerge well after the cochlea is mature and that each measure uniquely contributes to predicting participant demographics, indicating that sex differences arise from multiple central auditory processes.

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.

Improving reading skills in students with dyslexia: the efficacy of a sublexical training with rhythmic background.

The core deficit underlying developmental dyslexia (DD) has been identified in difficulties in dynamic and rapidly changing auditory information processing, which contribute to the development of impaired phonological representations for words. It has been argued that enhancing basic musical rhythm perception skills in children with DD may have a positive effect on reading abilities because music and language share common mechanisms and thus transfer effects from the former to the latter are expected to occur. A computer-assisted training, called Rhythmic Reading Training (RRT), was designed in which reading exercises are combined with rhythm background. Fourteen junior high school students with DD took part to 9 biweekly individual sessions of 30 min in which RRT was implemented. Reading improvements after the intervention period were compared with ones of a matched control group of 14 students with DD who received no intervention. Results indicated that RRT had a positive effect on both reading speed and accuracy and significant effects were found on short pseudo-words reading speed, long pseudo-words reading speed, high frequency long words reading accuracy, and text reading accuracy. No difference in rhythm perception between the intervention and control group were found. Findings suggest that rhythm facilitates the development of reading skill because of the temporal structure it imposes to word decoding.