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.

Positive impacts of early auditory training on cortical processing at an older age.

Progressive negative behavioral changes in normal aging are paralleled by a complex series of physical and functional declines expressed in the cerebral cortex. In studies conducted in the auditory domain, these degrading physical and functional cortical changes have been shown to be broadly reversed by intensive progressive training that improves the spectral and temporal resolution of acoustic inputs and suppresses behavioral distractors. Here we found older rats that were intensively trained on an attentionally demanding modulation-rate recognition task in young adulthood substantially retained training-driven improvements in temporal rate discrimination abilities over a subsequent 18-mo epoch-that is, forward into their older age. In parallel, this young-adult auditory training enduringly enhanced temporal and spectral information processing in their primary auditory cortices (A1). Substantially greater numbers of parvalbumin- and somatostatin-labeled inhibitory neurons (closer to the numbers recorded in young vigorous adults) were recorded in the A1 and hippocampus in old trained versus untrained age-matched rats. These results show that a simple form of training in young adulthood in this rat model enduringly delays the otherwise expected deterioration of the physical status and functional operations of the auditory nervous system, with evident training impacts generalized to the hippocampus.

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.

Got Rhythm? Better Inhibitory Control Is Linked with More Consistent Drumming and Enhanced Neural Tracking of the Musical Beat in Adult Percussionists and Nonpercussionists.

Musical rhythm engages motor and reward circuitry that is important for cognitive control, and there is evidence for enhanced inhibitory control in musicians. We recently revealed an inhibitory control advantage in percussionists compared with vocalists, highlighting the potential importance of rhythmic expertise in mediating this advantage. Previous research has shown that better inhibitory control is associated with less variable performance in simple sensorimotor synchronization tasks; however, this relationship has not been examined through the lens of rhythmic expertise. We hypothesize that the development of rhythm skills strengthens inhibitory control in two ways: by fine-tuning motor networks through the precise coordination of movements "in time" and by activating reward-based mechanisms, such as predictive processing and conflict monitoring, which are involved in tracking temporal structure in music. Here, we assess adult percussionists and nonpercussionists on inhibitory control, selective attention, basic drumming skills (self-paced, paced, and continuation drumming), and cortical evoked responses to an auditory stimulus presented on versus off the beat of music. Consistent with our hypotheses, we find that better inhibitory control is correlated with more consistent drumming and enhanced neural tracking of the musical beat. Drumming variability and the neural index of beat alignment each contribute unique predictive power to a regression model, explaining 57% of variance in inhibitory control. These outcomes present the first evidence that enhanced inhibitory control in musicians may be mediated by rhythmic expertise and provide a foundation for future research investigating the potential for rhythm-based training to strengthen cognitive function.

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.

Music training alters the course of adolescent auditory development.

Fundamental changes in brain structure and function during adolescence are well-characterized, but the extent to which experience modulates adolescent neurodevelopment is not. Musical experience provides an ideal case for examining this question because the influence of music training begun early in life is well-known. We investigated the effects of in-school music training, previously shown to enhance auditory skills, versus another in-school training program that did not focus on development of auditory skills (active control). We tested adolescents on neural responses to sound and language skills before they entered high school (pretraining) and again 3 y later. Here, we show that in-school music training begun in high school prolongs the stability of subcortical sound processing and accelerates maturation of cortical auditory responses. Although phonological processing improved in both the music training and active control groups, the enhancement was greater in adolescents who underwent music training. Thus, music training initiated as late as adolescence can enhance neural processing of sound and confer benefits for language skills. These results establish the potential for experience-driven brain plasticity during adolescence and demonstrate that in-school programs can engender these changes.

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.

Variations on the theme of musical expertise: cognitive and sensory processing in percussionists, vocalists and non-musicians.

Comparisons of musicians and non-musicians have revealed enhanced cognitive and sensory processing in musicians, with longitudinal studies suggesting these enhancements may be due in part to experience-based plasticity. Here, we investigate the impact of primary instrument on the musician signature of expertise by assessing three groups of young adults: percussionists, vocalists, and non-musician controls. We hypothesize that primary instrument engenders selective enhancements reflecting the most salient acoustic features to that instrument, whereas cognitive functions are enhanced regardless of instrument. Consistent with our hypotheses, percussionists show more precise encoding of the fast-changing acoustic features of speech than non-musicians, whereas vocalists have better frequency discrimination and show stronger encoding of speech harmonics than non-musicians. There were no strong advantages to specialization in sight-reading vs. improvisation. These effects represent subtle nuances to the signature since the musician groups do not differ from each other in these measures. Interestingly, percussionists outperform both non-musicians and vocalists in inhibitory control. Follow-up analyses reveal that within the vocalists and non-musicians, better proficiency on an instrument other than voice is correlated with better inhibitory control. Taken together, these outcomes suggest the more extensive engagement of motor systems during instrumental practice may be an important factor for enhancements in inhibitory control, consistent with evidence for overlapping neural circuitry involved in both motor and cognitive control. These findings contribute to the ongoing refinement of the musician signature of expertise and may help to inform the use of music in training and intervention to strengthen cognitive function.

Beyond Words: How Humans Communicate Through Sound.

Every day we communicate using complex linguistic and musical systems, yet these modern systems are the product of a much more ancient relationship with sound. When we speak, we communicate not only with the words we choose, but also with the patterns of sound we create and the movements that create them. From the natural rhythms of speech, to the precise timing characteristics of a consonant, these patterns guide our daily communication. By examining the principles of information processing that are common to speech and music, we peel back the layers to reveal the biological foundations of human communication through sound. Further, we consider how the brain's response to sound is shaped by experience, such as musical expertise, and implications for the treatment of communication disorders.

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.

Getting back on the beat: links between auditory-motor integration and precise auditory processing at fast time scales.

The auditory system is unique in its ability to precisely detect the timing of perceptual events and use this information to update motor plans, a skill that is crucial for language. However, the characteristics of the auditory system that enable this temporal precision are only beginning to be understood. Previous work has shown that participants who can tap consistently to a metronome have neural responses to sound with greater phase coherence from trial to trial. We hypothesized that this relationship is driven by a link between the updating of motor output by auditory feedback and neural precision. Moreover, we hypothesized that neural phase coherence at both fast time scales (reflecting subcortical processing) and slow time scales (reflecting cortical processing) would be linked to auditory-motor timing integration. To test these hypotheses, we asked participants to synchronize to a pacing stimulus, and then changed either the tempo or the timing of the stimulus to assess whether they could rapidly adapt. Participants who could rapidly and accurately resume synchronization had neural responses to sound with greater phase coherence. However, this precise timing was limited to the time scale of 10 ms (100 Hz) or faster; neural phase coherence at slower time scales was unrelated to performance on this task. Auditory-motor adaptation therefore specifically depends upon consistent auditory processing at fast, but not slow, time scales.

Bilingual enhancements have no socioeconomic boundaries.

To understand how socioeconomic status (SES) and bilingualism simultaneously operate on cognitive and sensory function, we examined executive control, language skills, and neural processing of sound in adolescents who differed in language experience (i.e. English monolingual or Spanish-English bilingual) and level of maternal education (a proxy for SES). We hypothesized that experience communicating in two languages provides an enriched linguistic environment that can bolster neural precision in subcortical auditory processing which, in turn, enhances cognitive and linguistic function, regardless of the adolescent's socioeconomic standing. Consistent with this, we report that adolescent bilinguals of both low and high SES demonstrate more stable neural responses, stronger phonemic decoding skills, and heightened executive control, relative to their monolingual peers. These results support the argument that bilingualism can bolster cognitive and neural function in low-SES children and suggest that strengthened neural response consistency provides a biological mechanism through which these enhancements occur.

Stability and plasticity of auditory brainstem function across the lifespan.

The human auditory brainstem is thought to undergo rapid developmental changes early in life until age ∼2 followed by prolonged stability until aging-related changes emerge. However, earlier work on brainstem development was limited by sparse sampling across the lifespan and/or averaging across children and adults. Using a larger dataset than past investigations, we aimed to trace more subtle variations in auditory brainstem function that occur normally from infancy into the eighth decade of life. To do so, we recorded auditory brainstem responses (ABRs) to a click stimulus and a speech syllable (da) in 586 normal-hearing healthy individuals. Although each set of ABR measures (latency, frequency encoding, response consistency, nonstimulus activity) has a distinct developmental profile, across all measures developmental changes were found to continue well past age 2. In addition to an elongated developmental trajectory and evidence for multiple auditory developmental processes, we revealed a period of overshoot during childhood (5-11 years old) for latency and amplitude measures, when the latencies are earlier and the amplitudes are greater than the adult value. Our data also provide insight into the capacity for experience-dependent auditory plasticity at different stages in life and underscore the importance of using age-specific norms in clinical and experimental applications.

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.