Auditory Temporal Processing Deficits Research Articles

Early Auditory Temporal Processing Deficit in Children with Autism Spectrum Disorder: The Research Domain Criteria Framework

Altered sensory processing especially in the auditory system is considered a typical observation in children with autism spectrum disorder (ASD). Auditory temporal processing is known to be impaired in ASD children. Although research suggests that auditory temporal processing abnormalities could be responsible for the core aspects of ASD, few studies have examined early time processing and their results have been conflicting. The present event-related potential (ERP) study investigated the early neural responses to duration and inter-stimulus interval (ISI) deviants in nonspeech contexts in children with ASD and a control group of typically developing (TD) children matched in terms of age and IQ. A passive auditory oddball paradigm was employed to elicit the mismatch negativity (MMN) for change detection considering both the duration and ISI-based stimulus. The MMN results showed that the ASD group had a relatively diminished amplitude and significant delayed latency in response to duration deviants. The findings are finally discussed in terms of hyper-hyposensitivity of auditory processing and the fact that the observed patterns may potentially act as risk factors for ASD development within the research domain criteria (RDoC) framework.

The Relative Contribution of Cochlear Synaptopathy and Reduced Inhibition to Age-Related Hearing Impairment for People With Normal Audiograms.

Older people often show auditory temporal processing deficits and speech-in-noise intelligibility difficulties even when their audiogram is clinically normal. The causes of such problems remain unclear. Some studies have suggested that for people with normal audiograms, age-related hearing impairments may be due to a cognitive decline, while others have suggested that they may be caused by cochlear synaptopathy. Here, we explore an alternative hypothesis, namely that age-related hearing deficits are associated with decreased inhibition. For human adults (N = 30) selected to cover a reasonably wide age range (25-59 years), with normal audiograms and normal cognitive function, we measured speech reception thresholds in noise (SRTNs) for disyllabic words, gap detection thresholds (GDTs), and frequency modulation detection thresholds (FMDTs). We also measured the rate of growth (slope) of auditory brainstem response wave-I amplitude with increasing level as an indirect indicator of cochlear synaptopathy, and the interference inhibition score in the Stroop color and word test (SCWT) as a proxy for inhibition. As expected, performance in the auditory tasks worsened (SRTNs, GDTs, and FMDTs increased), and wave-I slope and SCWT inhibition scores decreased with ageing. Importantly, SRTNs, GDTs, and FMDTs were not related to wave-I slope but worsened with decreasing SCWT inhibition. Furthermore, after partialling out the effect of SCWT inhibition, age was no longer related to SRTNs or GDTs and became less strongly related to FMDTs. Altogether, results suggest that for people with normal audiograms, age-related deficits in auditory temporal processing and speech-in-noise intelligibility are mediated by decreased inhibition rather than cochlear synaptopathy.

Amyloid Pathology in the Central Auditory Pathway of 5XFAD Mice Appears First in Auditory Cortex.

Effective treatment of Alzheimer's disease (AD) will hinge on early detection. This has led to the search for early biomarkers that use non-invasive testing. One possible early biomarker is auditory temporal processing deficits, which reflect central auditory pathway dysfunction and precede cognitive and memory declines in AD. Gap detection is a measure of auditory temporal processing, is impaired in human AD, and is also impaired in the 5XFAD mouse model of AD. Gap detection deficits appear as early as postnatal day 60 in 5XFAD mice, months before cognitive deficits or cell death, supporting gap detection as an early biomarker. However, it remains unclear how gap detection deficits relate to the progression of amyloid pathology in the auditory system. To determine the progression of amyloid pathology throughout the central auditory system and across age in 5XFAD mice. We quantified intracellular and extracellular antibody labelling of Aβ42 in 6 regions of the central auditory system from p14 to p150. Pathology appeared first in primary auditory cortex (A1) as intracellular accumulation of Aβ42 in layer 5 pyramidal neurons by age p21. Extracellular plaques appeared later, by age p90, in A1, medial geniculate body, and inferior colliculus. Auditory brainstem structures showed minimal amyloid pathology. We also observed pathology in the caudal pontine reticular nucleus, a brainstem structure that is outside of the central auditory pathway but which is involved in the acoustic startle reflex. These results suggest that Aβ42 accumulation, but not plaques, may impair gap detection.

The recognition of time-compressed speech as a function of age in listeners with cochlear implants or normal hearing.

Speech recognition is diminished when a listener has an auditory temporal processing deficit. Such deficits occur in listeners over 65 years old with normal hearing (NH) and with age-related hearing loss, but their source is still unclear. These deficits may be especially apparent when speech occurs at a rapid rate and when a listener is mostly reliant on temporal information to recognize speech, such as when listening with a cochlear implant (CI) or to vocoded speech (a CI simulation). Assessment of the auditory temporal processing abilities of adults with CIs across a wide range of ages should better reveal central or cognitive sources of age-related deficits with rapid speech because CI stimulation bypasses much of the cochlear encoding that is affected by age-related peripheral hearing loss. This study used time-compressed speech at four different degrees of time compression (0, 20, 40, and 60%) to challenge the auditory temporal processing abilities of younger, middle-aged, and older listeners with CIs or with NH. Listeners with NH were presented vocoded speech at four degrees of spectral resolution (unprocessed, 16, 8, and 4 channels). Results showed an interaction between age and degree of time compression. The reduction in speech recognition associated with faster rates of speech was greater for older adults than younger adults. The performance of the middle-aged listeners was more similar to that of the older listeners than to that of the younger listeners, especially at higher degrees of time compression. A measure of cognitive processing speed did not predict the effects of time compression. These results suggest that central auditory changes related to the aging process are at least partially responsible for the auditory temporal processing deficits seen in older listeners, rather than solely peripheral age-related changes.

Deficits in Acoustic Startle Reactivity and Auditory Temporal Processing after Traumatic Brain Injury.

Traumatic brain injury (TBI) exacts significant neurological and financial costs on patients and their families. In adult patients with moderate-to-severe TBI, central auditory impairments have been reported. These auditory impairments may interfere with language receptivity, as observed in children with developmental brain injury. Although rodent models of TBI have been widely used to examine behavioral outcomes, few studies have evaluated how TBI affects higher-order central auditory processing across a range of cue complexities. Here, auditory processing was assessed using a modified acoustic startle paradigm. We used a battery of progressively complex stimuli (single-tone, silent gaps in white noise, and frequency-modulated [FM] sweeps) in adult rats that received unilateral controlled cortical impact injury. TBI subjects showed significant reductions in acoustic startle absolute responses across nearly all stimuli, regardless of cue, duration of stimuli, or cue complexity. Despite this overall reduction of startle magnitudes in injured animals, the detection of single-tone stimuli was comparable between TBI and sham-injured subjects, indicating intact hearing after TBI. TBI subjects showed deficits in rapid gap (5 ms) and FM sweep (175 ms) detection, and, in contrast to shams, they did not improve on detecting silent gaps and FM sweeps across days of testing. Our findings provide evidence for both low-level (brainstem-mediated) and higher-order central auditory processing deficits in a rodent model of TBI, which parallel sensory impairments observed in TBI patients. The present findings support the use of modified pre-pule auditory detection paradigms to investigate clinically relevant processes in TBI.

Open-Set Phoneme Recognition Performance With Varied Temporal Cues in Younger and Older Cochlear Implant Users.

The goal of this study was to investigate the effect of age on phoneme recognition performance in which the stimuli varied in the amount of temporal information available in the signal. Chronological age is increasingly recognized as a factor that can limit the amount of benefit an individual can receive from a cochlear implant (CI). Central auditory temporal processing deficits in older listeners may contribute to the performance gap between younger and older CI users on recognition of phonemes varying in temporal cues. Phoneme recognition was measured at three stimulation rates (500, 900, and 1800 pulses per second) and two envelope modulation frequencies (50 Hz and unfiltered) in 20 CI participants ranging in age from 27 to 85 years. Speech stimuli were multiple word pairs differing in temporal contrasts and were presented via direct stimulation of the electrode array using an eight-channel continuous interleaved sampling strategy. Phoneme recognition performance was evaluated at each stimulation rate condition using both envelope modulation frequencies. Duration of deafness was the strongest subject-level predictor of phoneme recognition, with participants with longer durations of deafness having poorer performance overall. Chronological age did not predict performance for any stimulus condition. Additionally, duration of deafness interacted with envelope filtering. Participants with shorter durations of deafness were able to take advantage of higher frequency envelope modulations, while participants with longer durations of deafness were not. Age did not significantly predict phoneme recognition performance. In contrast, longer durations of deafness were associated with a reduced ability to utilize available temporal information within the signal to improve phoneme recognition performance.

Auditory temporal processing deficits in developmental dyslexia

Auditory temporal processing deficits in developmental dyslexia

Auditory Phenotypic Variability in Friedreich\u2019s Ataxia Patients

Auditory neural impairment is a key clinical feature of Friedreich’s Ataxia (FRDA). We aimed to characterize the phenotypical spectrum of the auditory impairment in FRDA in order to facilitate early identification and timely management of auditory impairment in FRDA patients and to explore the relationship between the severity of auditory impairment with genetic variables (the expansion size of GAA trinucleotide repeats, GAA1 and GAA2), when controlled for variables such as disease duration, severity of the disease and cognitive status. Twenty-seven patients with genetically confirmed FRDA underwent baseline audiological assessment (pure-tone audiometry, otoacoustic emissions, auditory brainstem response). Twenty of these patients had additional psychophysical auditory processing evaluation including an auditory temporal processing test (gaps in noise test) and a binaural speech perception test that assesses spatial processing (Listening in Spatialized Noise-Sentences Test). Auditory spatial and auditory temporal processing ability were significantly associated with the repeat length of GAA1. Patients with GAA1 greater than 500 repeats had more severe auditory temporal and spatial processing deficits, leading to poorer speech perception. Furthermore, the spatial processing ability was strongly correlated with the Montreal Cognitive Assessment (MoCA) score. To our knowledge, this is the first study to demonstrate an association between genotype and auditory spatial processing phenotype in patients with FRDA. Auditory temporal processing, neural sound conduction, spatial processing and speech perception were more severely affected in patients with GAA1 greater than 500 repeats. The results of our study may indicate that auditory deprivation plays a role in the development of mild cognitive impairment in FRDA patients.

Dysfunctional auditory gamma oscillations in developmental dyslexia: A potential target for a tACS-based intervention.

Interventions in developmental dyslexia typically consist of orthography-based reading and writing trainings. However, their efficacy is limited and, consequently, the symptoms persist into adulthood. Critical for this lack of efficacy is the still ongoing debate about the core deficit in dyslexia and its underlying neurobiological causes. There is ample evidence on phonological as well as auditory temporal processing deficits in dyslexia and, on the other hand, cortical gamma oscillations in the auditory cortex as functionally relevant for the extraction of linguistically meaningful information units from the acoustic signal. The present work aims to shed more light on the link between auditory gamma oscillations, phonological awareness, and literacy skills in dyslexia. By mean of EEG, individual gamma frequencies were assessed in a group of children and adolescents diagnosed with dyslexia as well as in an age-matched control group with typical literacy skills. Furthermore, phonological awareness was assessed in both groups, while in dyslexic participants also reading and writing performance was measured. We found significantly lower gamma peak frequencies as well as lower phonological awareness scores in dyslexic participants compared to age-matched controls. Additionally, results showed a positive correlation between the individual gamma frequency and phonological awareness. Our data suggest a hierarchical structure of neural gamma oscillations, phonological awareness, and literacy skills. Thereby, the results emphasize altered gamma oscillation not only as a core deficit in dyslexia but also as a potential target for future causal interventions. We discuss these findings considering non-invasive brain stimulation techniques and suggest transcranial alternating current stimulation as a promising approach to normalize dysfunctional oscillations in dyslexia.

Impact of Aging and the Electrode-to-Neural Interface on Temporal Processing Ability in Cochlear-Implant Users: Amplitude-Modulation Detection Thresholds.

Although cochlear implants (CIs) are a viable treatment option for severe hearing loss in adults of any age, older adults may be at a disadvantage compared with younger adults. CIs deliver signals that contain limited spectral information, requiring CI users to attend to the temporal information within the signal to recognize speech. Older adults are susceptible to acquiring auditory temporal processing deficits, presenting a potential age-related limitation for recognizing speech signals delivered by CIs. The goal of this study was to measure auditory temporal processing ability via amplitude-modulation (AM) detection as a function of age in CI users. The contribution of the electrode-to-neural interface, in addition to age, was estimated using electrically evoked compound action potential (ECAP) amplitude growth functions. Within each participant, two electrodes were selected: one with the steepest ECAP slope and one with the shallowest ECAP slope, in order to represent electrodes with varied estimates of the electrode-to-neural interface. Single-electrode AM detection thresholds were measured using direct stimulation at these two electrode locations. Results revealed that AM detection ability significantly declined as a function of chronological age. ECAP slope did not significantly impact AM detection, but ECAP slope decreased (became shallower) with increasing age, suggesting that factors influencing the electrode-to-neural interface change with age. Results demonstrated a significant negative impact of chronological age on auditory temporal processing. The locus of the age-related limitation (peripheral vs. central origin), however, is difficult to evaluate because the peripheral influence (ECAPs) was correlated with the central factor (age).

Impact of Aging and the Electrode-to-Neural Interface on Temporal Processing Ability in Cochlear-Implant Users: Gap Detection Thresholds.

Accurate processing of temporal information is critical to understanding speech through a cochlear implant (CI). This has potential implications for the growing population of CI users who are ≥65 years of age because of age-related auditory temporal processing deficits. The goal of this study was to measure temporal processing ability in a gap detection task in younger, middle-aged, and older CI users and to determine the relative contributions of chronological age and peripheral neural survival to performance. Single-electrode gap detection thresholds (GDTs) were measured using direct stimulation at five electrode locations and three electrical stimulation rates. The relationship between peripheral status (e.g., electrode-to-neural interface) and GDTs was assessed by the slope of the electrically evoked compound action potential (ECAP) amplitude growth function. Results showed that ECAP slope was the strongest subject-level predictor of GDTs. Steeper ECAP slopes, which are partially indicative of better peripheral function, were associated with better GDTs in younger participants. However, ECAP slope significantly interacted with stimulation rate and age, suggesting that ECAP slopes were not predictive of GDTs in middle-aged and older participants at some stimulation rates. ECAP slope was also related to age, with middle-aged and older participants exhibiting relatively shallow slopes and smaller ranges of slopes compared with younger participants. This pattern of ECAP results limited the evaluation of the independent effects of aging per se and peripheral status on temporal processing ability.

Temporal Coding of Single Auditory Nerve Fibers Is Not Degraded in Aging Gerbils.

People suffering from age-related hearing loss typically present with deficits in temporal processing tasks. Temporal processing deficits have also been shown in single-unit studies at the level of the auditory brainstem, midbrain, and cortex of aged animals. In this study, we explored whether temporal coding is already affected at the level of the input to the central auditory system. Single-unit auditory nerve fiber recordings were obtained from 41 Mongolian gerbils of either sex, divided between young, middle-aged, and old gerbils. Temporal coding quality was evaluated as vector strength in response to tones at best frequency, and by constructing shuffled and cross-stimulus autocorrelograms, and reverse correlations, from responses to 1 s noise bursts at 10-30 dB sensation level (dB above threshold). At comparable sensation levels, all measures showed that temporal coding was not altered in auditory nerve fibers of aging gerbils. Furthermore, both temporal fine structure and envelope coding remained unaffected. However, spontaneous rates were decreased in aging gerbils. Importantly, despite elevated pure tone thresholds, the frequency tuning of auditory nerve fibers was not affected. These results suggest that age-related temporal coding deficits arise more centrally, possibly due to a loss of auditory nerve fibers (or their peripheral synapses) but not due to qualitative changes in the responses of remaining auditory nerve fibers. The reduced spontaneous rate and elevated thresholds, but normal frequency tuning, of aged auditory nerve fibers can be explained by the well known reduction of endocochlear potential due to strial dysfunction in aged gerbils.SIGNIFICANCE STATEMENT As our society ages, age-related hearing deficits become ever more prevalent. Apart from decreased hearing sensitivity, elderly people often suffer from a reduced ability to communicate in daily settings, which is thought to be caused by known age-related deficits in auditory temporal processing. The current study demonstrated, using several different stimuli and analysis techniques, that these putative temporal processing deficits are not apparent in responses of single-unit auditory nerve fibers of quiet-aged gerbils. This suggests that age-related temporal processing deficits may develop more central to the auditory nerve, possibly due to a reduced population of active auditory nerve fibers, which will be of importance for the development of treatments for age-related hearing disorders.

Mice heterozygous for the Cdh23/Ahl1 mutation show age-related deficits in auditory temporal processing

A mutation in the Cdh23 gene is implicated in both syndromic and nonsyndromic hearing loss in humans and age-related hearing loss in C57BL/6 mice. It is generally assumed that human patients (as well as mouse models) only have a hearing loss phenotype if the mutation is homozygous. However, a major complaint for patients with a hearing disability is a reduced speech intelligibility that may be related to temporal processing deficits rather than just elevated thresholds. In this study, we used the amplitude modulation following response (AMFR) to test whether mice heterozygous for Cdh23735A > G have an auditory phenotype that includes temporal processing deficits. The hearing of mice heterozygous for the Cdh23735A > G mutation was compared with age-matched mice homozygous for either the mutation or the wild type in 3 cohorts of mice of both sexes at 2-3, 6, and 12 months of age. The AMFR technique was used to generate objective hearing thresholds for all mice across their range of hearing and to test their temporal processing. We found a genotype-dependent hearing loss in mice homozygous for the mutation starting at 5–11 weeks of age, an age when mice on the C57BL/6 background are often presumed to have normal hearing. The heterozygous animals retained normal hearing thresholds up to one year of age. Nevertheless, the heterozygous animals showed a decline in temporal processing abilities at one year of age that was independent of their hearing thresholds. These results suggest that mice heterozygous for the Cdh23 mutation do not have truly normal hearing.

5XFAD Mice Show Early Onset Gap Detection Deficits.

Alzheimer's patients show auditory temporal processing deficits very early in disease progression, before the onset of major cognitive impairments. In addition to potentially contributing to speech perception and communication deficits in patients, this also represents a potential early biomarker for Alzheimer's. For this reason, tests of temporal processing such as gap detection have been proposed as an early diagnosis tool. For a biomarker such as gap detection deficits to have maximum clinical value, it is important to understand what underlying neuropathology it reflects. For example, temporal processing deficits could arise from alterations at cortical, midbrain, or brainstem levels. Mouse models of Alzheimer's disease can provide the ability to reveal in detail the molecular and circuit pathology underlying disease symptoms. Here we tested whether 5XFAD mice, a leading Alzheimer's mouse model, exhibit impaired temporal processing. We found that 5XFAD mice showed robust gap detection deficits. Gap detection deficits were first detectable at about 2 months of age and became progressively worse, especially for males and for longer gap durations. We conclude that 5XFAD mice are well-suited to serve as a model for understanding the circuit mechanisms that contribute to Alzheimer's-related gap detection deficits.

Auditory temporal processing, reading, and phonological awareness among aging adults

Auditory temporal processing (ATP) has been related in the literature to both speech perception as well as reading and phonological awareness. In aging adults, it is known to be related to difficulties in speech perception. In the present study, we aimed to test whether an age-related deficit in ATP would also be accompanied by poor reading and phonological awareness. Thirty-eight aging adults were compared to 55 readers with dyslexia and 42 young normal readers on temporal order judgment (TOJ), speech perception, reading, and phonological awareness tests. Aging adults had longer TOJ thresholds than young normal readers, but shorter than readers with dyslexia; however, they had lower speech perception accuracy than both groups. Phonological awareness of the aging adults was better than readers with dyslexia, but poorer than young normal readers, although their reading accuracy was similar to that of the young controls. This is the first report on poor phonological awareness among aging adults. Suprisingly, it was not accompanied by difficulties in reading ability, and might instead be related to aging adults' difficulties in speech perception. This newly discovered relationship between ATP and phonological awareness among aging adults appears to extend the existing understanding of this relationship, and suggests it should be explored in other groups with ATP deficits.

Synaptopathy in the Aging Cochlea: Characterizing Early-Neural Deficits in Auditory Temporal Envelope Processing.

Aging listeners, even in the absence of overt hearing loss measured as changes in hearing thresholds, often experience impairments processing temporally complex sounds such as speech in noise. Recent evidence has shown that normal aging is accompanied by a progressive loss of synapses between inner hair cells and auditory nerve fibers. The role of this cochlear synaptopathy in degraded temporal processing with age is not yet understood. Here, we used population envelope following responses, along with other hair cell- and neural-based measures from an age-graded series of male and female CBA/CaJ mice to study changes in encoding stimulus envelopes. By comparing responses obtained before and after the application of the neurotoxin ouabain to the inner ear, we demonstrate that we can study changes in temporal processing on either side of the cochlear synapse. Results show that deficits in neural coding with age emerge at the earliest neural stages of auditory processing and are correlated with the degree of cochlear synaptopathy. These changes are seen before losses in neural thresholds and particularly affect the suprathreshold processing of sound. Responses obtained from more central sources show smaller differences with age, suggesting compensatory gain. These results show that progressive cochlear synaptopathy is accompanied by deficits in temporal coding at the earliest neural generators and contribute to the suprathreshold sound processing deficits observed with age.SIGNIFICANCE STATEMENT Aging listeners often experience difficulty hearing and understanding speech in noisy conditions. The results described here suggest that age-related loss of cochlear synapses may be a significant contributor to those performance declines. We observed aberrant neural coding of sounds in the early auditory pathway, which was accompanied by and correlated with an age-progressive loss of synapses between the inner hair cells and the auditory nerve. Deficits first appeared before changes in hearing thresholds and were largest at higher sound levels relevant to real world communication. The noninvasive tests described here may be adapted to detect cochlear synaptopathy in the clinical setting.

Effect of auditory temporal processing training on behavioral and electrophysiological functions in central presbycusis

ObjectiveAge-related changes in the central auditory system, particularly auditory temporal processing abilities, were considered among most important factors affecting speech understanding performance in older adults. Once these factors are identified, clinical management procedures could be developed for prevention and treatment. The aim of this study was to determine the effects of short-term auditory training on the behavioral and electrophysiological measurements of auditory function in individuals with age-related temporal processing deficit.Participants and methodsA prospective study of 20 individuals aged 60–67 years with either normal or bilateral symmetric high-frequency hearing loss was conducted. Evaluations of auditory temporal processing using behavioral tests (Pitch Discrimination Test, Pitch Pattern Sequence Test, Auditory Fusion Test-Revised, and Time Compressed Speech Test), P300 potential, and the administration of ‘Amsterdam inventory for auditory disability and handicap’ were performed before and after short-term auditory training.ResultsAll participants demonstrated poor pretraining Pitch Pattern Sequence Test results which were significantly improved after remediation. All patients showed normal pretraining performance on Pitch Discrimination Test, Auditory Fusion Test-Revised, and Time Compressed Speech Test tests. There was a statistically significant increase in P300 amplitude and shortening in latency after remediation.ConclusionShort-term auditory training in older adults with auditory temporal processing deficit led to improvements in temporal sequencing skills and communication in noisy environments. P300 potential has been proved to be an objective indicator of neurophysiologic changes in the central auditory system resulting from auditory experience.RecommendationShort-term auditory training is an efficient rehabilitative tool for elderly people with auditory temporal processing deficit. However, maintenance of treatment effects over time should be evaluated.

Age-related deficits in auditory temporal processing: unique contributions of neural dyssynchrony and slowed neuronal processing

This study was guided by the hypothesis that the aging central nervous system progressively loses its ability to process rapid acoustic changes that are important for speech recognition. Specifically, we hypothesized that age-related deficits in neural synchrony and neuronal oscillatory activity occur independently in older adults and disrupt auditory temporal processing. Neural synchrony is largely dependent on phase locking within the central auditory pathway, beginning at the auditory nerve. In contrast, the resonance characteristics of oscillatory activity are dependent on the integrity and structure of long range cortical connections. We tested our hypotheses by assessing age-related differences in electrophysiologic correlates of neural synchrony and peak oscillatory frequency in younger and older adults with normal hearing and determining their associations with a behavioral measure of gap detection. Phase-locking values were smaller (poorer neural synchrony) and peak alpha frequency was lower for older than younger adults and decreased as gap detection thresholds increased; variations in phase-locking values and peak alpha frequency uniquely predicted gap detection thresholds. These effects were driven, in large part, by associations in older adults. These results reveal dissociable neural mechanisms associated with distinct underlying pathology that may differentially be present in older adults and contribute to auditory processing declines.

Pb exposure prolongs the time period for postnatal transient uptake of 5-HT by murine LSO neurons

Pb exposure is associated with cognitive deficits including Attention Deficit Hyperactivity Disorder (ADHD) in children and alters auditory temporal processing in humans and animals. Serotonin has been implicated in auditory temporal processing and previous studies from our laboratory have demonstrated that developmental Pb decreases expression of serotonin (5-HT) in the adult murine lateral superior olive (LSO). During development, certain non-serotonergic sensory neurons, including auditory LSO neurons, transiently take up 5-HT through the serotonin reuptake transporter (SERT). The uptake of 5-HT is important for development of sensory systems. This study examines the effect of Pb on the serotonergic system in the LSO of the early postnatal mouse. Mice were exposed to moderate Pb (0.01mM) or high Pb (0.1mM) throughout gestation and postnatal day 4 (P4) and P8. We found that Pb exposure prolongs the normal developmental expression of 5-HT by LSO neurons and this is correlated with expression of SERT on LSO cell bodies. The prolonged expression of 5-HT by postnatal LSO neurons is correlated with decreased synaptic immunolabeling within the LSO. This Pb-associated decrease in synaptic density within the LSO could contribute to the auditory temporal processing deficits and cognitive deficits associated with developmental Pb exposure.

Evidence of degraded representation of speech in noise, in the aging midbrain and cortex.

Humans have a remarkable ability to track and understand speech in unfavorable conditions, such as in background noise, but speech understanding in noise does deteriorate with age. Results from several studies have shown that in younger adults, low-frequency auditory cortical activity reliably synchronizes to the speech envelope, even when the background noise is considerably louder than the speech signal. However, cortical speech processing may be limited by age-related decreases in the precision of neural synchronization in the midbrain. To understand better the neural mechanisms contributing to impaired speech perception in older adults, we investigated how aging affects midbrain and cortical encoding of speech when presented in quiet and in the presence of a single-competing talker. Our results suggest that central auditory temporal processing deficits in older adults manifest in both the midbrain and in the cortex. Specifically, midbrain frequency following responses to a speech syllable are more degraded in noise in older adults than in younger adults. This suggests a failure of the midbrain auditory mechanisms needed to compensate for the presence of a competing talker. Similarly, in cortical responses, older adults show larger reductions than younger adults in their ability to encode the speech envelope when a competing talker is added. Interestingly, older adults showed an exaggerated cortical representation of speech in both quiet and noise conditions, suggesting a possible imbalance between inhibitory and excitatory processes, or diminished network connectivity that may impair their ability to encode speech efficiently.