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.

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.

Listening in the Moment: How Bilingualism Interacts With Task Demands to Shape Active Listening.

While there is evidence for bilingual enhancements of inhibitory control and auditory processing, two processes that are fundamental to daily communication, it is not known how bilinguals utilize these cognitive and sensory enhancements during real-world listening. To test our hypothesis that bilinguals engage their enhanced cognitive and sensory processing in real-world listening situations, bilinguals and monolinguals performed a selective attention task involving competing talkers, a common demand of everyday listening, and then later passively listened to the same competing sentences. During the active and passive listening periods, evoked responses to the competing talkers were collected to understand how online auditory processing facilitates active listening and if this processing differs between bilinguals and monolinguals. Additionally, participants were tested on a separate measure of inhibitory control to see if inhibitory control abilities related with performance on the selective attention task. We found that although monolinguals and bilinguals performed similarly on the selective attention task, the groups differed in the neural and cognitive processes engaged to perform this task, compared to when they were passively listening to the talkers. Specifically, during active listening monolinguals had enhanced cortical phase consistency while bilinguals demonstrated enhanced subcortical phase consistency in the response to the pitch contours of the sentences, particularly during passive listening. Moreover, bilinguals' performance on the inhibitory control test related with performance on the selective attention test, a relationship that was not seen for monolinguals. These results are consistent with the hypothesis that bilinguals utilize inhibitory control and enhanced subcortical auditory processing in everyday listening situations to engage with sound in ways that are different than monolinguals.

Sex differences in auditory processing vary across estrous cycle.

In humans, females process a sound's harmonics more robustly than males. As estrogen regulates auditory plasticity in a sex-specific manner in seasonally breeding animals, estrogen signaling is one hypothesized mechanism for this difference in humans. To investigate whether sex differences in harmonic encoding vary similarly across the reproductive cycle of mammals, we recorded frequency-following responses (FFRs) to a complex sound in male and female rats. Female FFRs were collected during both low and high levels of circulating estrogen during the estrous cycle. Overall, female rodents had larger harmonic encoding than male rodents, and greater harmonic strength was seen during periods of greater estrogen production in the females. These results argue that hormonal differences, specifically estrogen, underlie sex differences in harmonic encoding in rodents and suggest that a similar mechanism may underlie differences seen in humans.

Auditory Cortical Changes Precede Brainstem Changes During Rapid Implicit Learning: Evidence From Human EEG.

The auditory system is sensitive to stimulus regularities such as frequently occurring sounds and sound combinations. Evidence of regularity detection can be seen in how neurons across the auditory network, from brainstem to cortex, respond to the statistical properties of the soundscape, and in the rapid learning of recurring patterns in their environment by children and adults. Although rapid auditory learning is presumed to involve functional changes to the auditory network, the chronology and directionality of changes are not well understood. To study the mechanisms by which this learning occurs, auditory brainstem and cortical activity was simultaneously recorded via electroencephalogram (EEG) while young adults listened to novel sound streams containing recurring patterns. Neurophysiological responses were compared between easier and harder learning conditions. Collectively, the behavioral and neurophysiological findings suggest that cortical and subcortical structures each provide distinct contributions to auditory pattern learning, but that cortical sensitivity to stimulus patterns likely precedes subcortical sensitivity.

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.

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.

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.

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.

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.

Analyzing the FFR: A tutorial for decoding the richness of auditory function.

The frequency-following response, or FFR, is a neurophysiological response to sound that precisely reflects the ongoing dynamics of sound. It can be used to study the integrity and malleability of neural encoding of sound across the lifespan. Sound processing in the brain can be impaired with pathology and enhanced through expertise. The FFR can index linguistic deprivation, autism, concussion, and reading impairment, and can reflect the impact of enrichment with short-term training, bilingualism, and musicianship. Because of this vast potential, interest in the FFR has grown considerably in the decade since our first tutorial. Despite its widespread adoption, there remains a gap in the current knowledge of its analytical potential. This tutorial aims to bridge this gap. Using recording methods we have employed for the last 20 + years, we have explored many analysis strategies. In this tutorial, we review what we have learned and what we think constitutes the most effective ways of capturing what the FFR can tell us. The tutorial covers FFR components (timing, fundamental frequency, harmonics) and factors that influence FFR (stimulus polarity, response averaging, and stimulus presentation/recording jitter). The spotlight is on FFR analyses, including ways to analyze FFR timing (peaks, autocorrelation, phase consistency, cross-phaseogram), magnitude (RMS, SNR, FFT), and fidelity (stimulus-response correlations, response-to-response correlations and response consistency). The wealth of information contained within an FFR recording brings us closer to understanding how the brain reconstructs our sonic world.

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.