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.

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.

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.

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.

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.

Auditory Processing in Noise: A Preschool Biomarker for Literacy.

Learning to read is a fundamental developmental milestone, and achieving reading competency has lifelong consequences. Although literacy development proceeds smoothly for many children, a subset struggle with this learning process, creating a need to identify reliable biomarkers of a child's future literacy that could facilitate early diagnosis and access to crucial early interventions. Neural markers of reading skills have been identified in school-aged children and adults; many pertain to the precision of information processing in noise, but it is unknown whether these markers are present in pre-reading children. Here, in a series of experiments in 112 children (ages 3-14 y), we show brain-behavior relationships between the integrity of the neural coding of speech in noise and phonology. We harness these findings into a predictive model of preliteracy, revealing that a 30-min neurophysiological assessment predicts performance on multiple pre-reading tests and, one year later, predicts preschoolers' performance across multiple domains of emergent literacy. This same neural coding model predicts literacy and diagnosis of a learning disability in school-aged children. These findings offer new insight into the biological constraints on preliteracy during early childhood, suggesting that neural processing of consonants in noise is fundamental for language and reading development. Pragmatically, these findings open doors to early identification of children at risk for language learning problems; this early identification may in turn facilitate access to early interventions that could prevent a life spent struggling to read.

Children with autism spectrum disorder have unstable neural responses to sound.

Autism spectrum disorder (ASD) is diverse, manifesting in a wide array of phenotypes. However, a consistent theme is reduced communicative and social abilities. Auditory processing deficits have been shown in individuals with ASD-these deficits may play a role in the communication difficulties ASD individuals experience. Specifically, children with ASD have delayed neural timing and poorer tracking of a changing pitch relative to their typically developing peers. Given that accurate processing of sound requires highly coordinated and consistent neural activity, we hypothesized that these auditory processing deficits stem from a failure to respond to sound in a consistent manner. Therefore, we predicted that individuals with ASD have reduced neural stability in response to sound. We recorded the frequency-following response (FFR), an evoked response that mirrors the acoustic features of its stimulus, of high-functioning children with ASD age 7-13 years. Evident across multiple speech stimuli, children with ASD have less stable FFRs to speech sounds relative to their typically developing peers. This reduced auditory stability could contribute to the language and communication profiles observed in individuals with ASD.

Individual Differences in Human Auditory Processing: Insights From Single-Trial Auditory Midbrain Activity in an Animal Model.

Auditory-evoked potentials are classically defined as the summations of synchronous firing along the auditory neuraxis. Converging evidence supports a model whereby timing jitter in neural coding compromises listening and causes variable scalp-recorded potentials. Yet the intrinsic noise of human scalp recordings precludes a full understanding of the biological origins of individual differences in listening skills. To delineate the mechanisms contributing to these phenomena, in vivo extracellular activity was recorded from inferior colliculus in guinea pigs to speech in quiet and noise. Here we show that trial-by-trial timing jitter is a mechanism contributing to auditory response variability. Identical variability patterns were observed in scalp recordings in human children, implicating jittered timing as a factor underlying reduced coding of dynamic speech features and speech in noise. Moreover, intertrial variability in human listeners is tied to language development. Together, these findings suggest that variable timing in inferior colliculus blurs the neural coding of speech in noise, and propose a consequence of this timing jitter for human behavior. These results hint both at the mechanisms underlying speech processing in general, and at what may go awry in individuals with listening difficulties.

Difficulty hearing in noise: a sequela of concussion in children.

OBJECTIVE: Concussions can result in auditory processing deficits even in the absence of hearing loss. In children and adolescents, the extent to which these impairments have functional consequences for everyday listening, such as the ability to understand speech in noisy environments, is unknown. RESEARCH DESIGN: Case-control study. SUBJECTS AND METHODS: Forty youth comprised the participants: 20 had sustained a concussion and were recovering from their injury, and 20 controls had sustained non-concussive orthopaedic (e.g. musculoskeletal) injuries. All were evaluated on the Hearing in Noise Test, an audiologic index of the ability to hear sentences in adverse listening conditions. RESULTS: Children and adolescents recovering from concussions demonstrated an overall impaired ability to perceive speech in noisy backgrounds compared to a peer control group. This deficit also emerged across trials in the most taxing listening condition, and with respect to published, age-normative values. CONCLUSIONS: Functional listening skills-such as the ability to understand speech in noise, and the ability to sustain performance over time in taxing auditory conditions-may be compromised in children with concussions. These impairments may exacerbate cognitive and academic challenges associated with concussion injuries, and should be considered in return-to-learn and return-to-play decisions.

Individual Differences in Rhythm Skills: Links with Neural Consistency and Linguistic Ability.

Durational patterns provide cues to linguistic structure, thus so variations in rhythm skills may have consequences for language development. Understanding individual differences in rhythm skills, therefore, could help explain variability in language abilities across the population. We investigated the neural foundations of rhythmic proficiency and its relation to language skills in young adults. We hypothesized that rhythmic abilities can be characterized by at least two constructs, which are tied to independent language abilities and neural profiles. Specifically, we hypothesized that rhythm skills that require integration of information across time rely upon the consistency of slow, low-frequency auditory processing, which we measured using the evoked cortical response. On the other hand, we hypothesized that rhythm skills that require fine temporal precision rely upon the consistency of fast, higher-frequency auditory processing, which we measured using the frequency-following response. Performance on rhythm tests aligned with two constructs: rhythm sequencing and synchronization. Rhythm sequencing and synchronization were linked to the consistency of slow cortical and fast frequency-following responses, respectively. Furthermore, whereas rhythm sequencing ability was linked to verbal memory and reading, synchronization ability was linked only to nonverbal auditory temporal processing. Thus, rhythm perception at different time scales reflects distinct abilities, which rely on distinct auditory neural resources. In young adults, slow rhythmic processing makes the more extensive contribution to language skills.

Beat synchronization predicts neural speech encoding and reading readiness in preschoolers.

Temporal cues are important for discerning word boundaries and syllable segments in speech; their perception facilitates language acquisition and development. Beat synchronization and neural encoding of speech reflect precision in processing temporal cues and have been linked to reading skills. In poor readers, diminished neural precision may contribute to rhythmic and phonological deficits. Here we establish links between beat synchronization and speech processing in children who have not yet begun to read: preschoolers who can entrain to an external beat have more faithful neural encoding of temporal modulations in speech and score higher on tests of early language skills. In summary, we propose precise neural encoding of temporal modulations as a key mechanism underlying reading acquisition. Because beat synchronization abilities emerge at an early age, these findings may inform strategies for early detection of and intervention for language-based learning disabilities.

Reversal of age-related neural timing delays with training.

Neural slowing is commonly noted in older adults, with consequences for sensory, motor, and cognitive domains. One of the deleterious effects of neural slowing is impairment of temporal resolution; older adults, therefore, have reduced ability to process the rapid events that characterize speech, especially in noisy environments. Although hearing aids provide increased audibility, they cannot compensate for deficits in auditory temporal processing. Auditory training may provide a strategy to address these deficits. To that end, we evaluated the effects of auditory-based cognitive training on the temporal precision of subcortical processing of speech in noise. After training, older adults exhibited faster neural timing and experienced gains in memory, speed of processing, and speech-in-noise perception, whereas a matched control group showed no changes. Training was also associated with decreased variability of brainstem response peaks, suggesting a decrease in temporal jitter in response to a speech signal. These results demonstrate that auditory-based cognitive training can partially restore age-related deficits in temporal processing in the brain; this plasticity in turn promotes better cognitive and perceptual skills.

Music enrichment programs improve the neural encoding of speech in at-risk children.

Musicians are often reported to have enhanced neurophysiological functions, especially in the auditory system. Musical training is thought to improve nervous system function by focusing attention on meaningful acoustic cues, and these improvements in auditory processing cascade to language and cognitive skills. Correlational studies have reported musician enhancements in a variety of populations across the life span. In light of these reports, educators are considering the potential for co-curricular music programs to provide auditory-cognitive enrichment to children during critical developmental years. To date, however, no studies have evaluated biological changes following participation in existing, successful music education programs. We used a randomized control design to investigate whether community music participation induces a tangible change in auditory processing. The community music training was a longstanding and successful program that provides free music instruction to children from underserved backgrounds who stand at high risk for learning and social problems. Children who completed 2 years of music training had a stronger neurophysiological distinction of stop consonants, a neural mechanism linked to reading and language skills. One year of training was insufficient to elicit changes in nervous system function; beyond 1 year, however, greater amounts of instrumental music training were associated with larger gains in neural processing. We therefore provide the first direct evidence that community music programs enhance the neural processing of speech in at-risk children, suggesting that active and repeated engagement with sound changes neural function.

Development of subcortical speech representation in human infants.

Previous studies have evaluated representation of the fundamental frequency (F0) in the frequency following response (FFR) of infants, but the development of other aspects of the FFR, such as timing and harmonics, has not yet been examined. Here, FFRs were recorded to a speech syllable in 28 infants, ages three to ten months. The F0 amplitude of the response was variable among individuals but was strongly represented in some infants as young as three months of age. The harmonics, however, showed a systematic increase in amplitude with age. In the time domain, onset, offset, and inter-peak latencies decreased with age. These results are consistent with neurophysiological studies indicating that (1) phase locking to lower frequency sounds emerges earlier in life than phase locking to higher frequency sounds and (2) myelination continues to increase in the first year of life. Early representation of low frequencies may reflect greater exposure to low frequency stimulation in utero. The improvement in temporal precision likely parallels an increase in the efficiency of neural transmission accompanied by exposure to speech during the first year of life.

Older adults benefit from music training early in life: biological evidence for long-term training-driven plasticity.

Aging results in pervasive declines in nervous system function. In the auditory system, these declines include neural timing delays in response to fast-changing speech elements; this causes older adults to experience difficulty understanding speech, especially in challenging listening environments. These age-related declines are not inevitable, however: older adults with a lifetime of music training do not exhibit neural timing delays. Yet many people play an instrument for a few years without making a lifelong commitment. Here, we examined neural timing in a group of human older adults who had nominal amounts of music training early in life, but who had not played an instrument for decades. We found that a moderate amount (4-14 years) of music training early in life is associated with faster neural timing in response to speech later in life, long after training stopped (>40 years). We suggest that early music training sets the stage for subsequent interactions with sound. These experiences may interact over time to sustain sharpened neural processing in central auditory nuclei well into older age.

Aging affects neural precision of speech encoding.

Older adults frequently report they can hear what is said but cannot understand the meaning, especially in noise. This difficulty may arise from the inability to process rapidly changing elements of speech. Aging is accompanied by a general slowing of neural processing and decreased neural inhibition, both of which likely interfere with temporal processing in auditory and other sensory domains. Age-related reductions in inhibitory neurotransmitter levels and delayed neural recovery can contribute to decreases in the temporal precision of the auditory system. Decreased precision may lead to neural timing delays, reductions in neural response magnitude, and a disadvantage in processing the rapid acoustic changes in speech. The auditory brainstem response (ABR), a scalp-recorded electrical potential, is known for its ability to capture precise neural synchrony within subcortical auditory nuclei; therefore, we hypothesized that a loss of temporal precision results in subcortical timing delays and decreases in response consistency and magnitude. To assess this hypothesis, we recorded ABRs to the speech syllable /da/ in normal hearing younger (18-30 years old) and older (60-67 years old) adult humans. Older adults had delayed ABRs, especially in response to the rapidly changing formant transition, and greater response variability. We also found that older adults had decreased phase locking and smaller response magnitudes than younger adults. Together, our results support the theory that older adults have a loss of temporal precision in the subcortical encoding of sound, which may account, at least in part, for their difficulties with speech perception.

Effects of hearing loss on the subcortical representation of speech cues.

Individuals with sensorineural hearing loss often report frustration with speech being loud but not clear, especially in background noise. Despite advanced digital technology, hearing aid users may resort to removing their hearing aids in noisy environments due to the perception of excessive loudness. In an animal model, sensorineural hearing loss results in greater auditory nerve coding of the stimulus envelope, leading to a relative deficit of stimulus fine structure. Based on the hypothesis that brainstem encoding of the temporal envelope is greater in humans with sensorineural hearing loss, speech-evoked brainstem responses were recorded in normal hearing and hearing impaired age-matched groups of older adults. In the hearing impaired group, there was a disruption in the balance of envelope-to-fine structure representation compared to that of the normal hearing group. This imbalance may underlie the difficulty experienced by individuals with sensorineural hearing loss when trying to understand speech in background noise. This finding advances the understanding of the effects of sensorineural hearing loss on central auditory processing of speech in humans. Moreover, this finding has clinical potential for developing new amplification or implantation technologies, and in developing new training regimens to address this relative deficit of fine structure representation.

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.

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.

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.