Peripheral and brainstem auditory function in paroxysmal (px) White Leghorn chicks

The paroxysmal (px) chick is a mutant White Leghorn (Gallus domesticus) which appears normal at hatching and during the subsequent week. By ca. 8 days posthatching, various symptoms develop, of which the most obvious are depressed food intake (anorexia) and audiogenic seizures. Histological evidence suggests that central auditory and vestibular nuclei and fiber tracts begin to degenerate prior to seizure onset. This degeneration, which affects central and peripheral components of both systems, becomes increasingly severe over time although auditory stimulation continues to elicit seizures. Characterization and analysis of peripheral and brainstem auditory response to auditory stimuli indicated that major response differences between px and normal chicks exist in peaks reflecting brainstem activity (P3A, P3B, P4A, P5A). In 5 of 8 px chicks, these later response peaks were either grossly abnormal in terms of amplitude and latency (including amplitude input/output functions) or often entirely absent. Early peaks (P1A and P2A), however, in px waveforms were normal in morphology and amplitude, indicating normal function of peripheral auditory structures. Although lower body temperature of px chicks may account for some of the longer latencies observed, other abnormalities (e.g. absence of peaks) could not be produced in normal birds by induced hypothermia.     

Characteristic findings of auditory brainstem response and otoacoustic emission in the Bronx waltzer mouse

Auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs) were evaluated serially from 1 to 22 months in Bronx waltzer homozygotes (bv/bv), heterozygotes (+/bv) and control (+/+) mice, which were differentiated by means of PCR of marker DNA (D5Mit209). The wave IV threshold of the click-evoked ABR was higher than the DPOAE threshold with the DP growth method in each bv/bv, although the two thresholds were almost the same in the +/+ group. The DP value at 2f₁ − f₂ in the bv/bv showed an apparent decrease at 2 to 3 months of age with 80 dB SPL stimulation using f₂ frequency 7996 Hz and frequency ratio f₂/f₁ = 1.22, compared to control or heterozygote mice. It was characteristic that the 2f₂ − f₁ DP signal-to-noise ratio (SNR) value was more preserved from 80 to 60 dB SPL than the 2f₁ − f₂ DP value at f₂ frequency 7996 Hz in most bv/bv, however, control mice showed almost the same levels of 2f₁ − f₂ and 2f₂ − f₁ SNR value at both f₂ frequencies of 6006 and 7996 Hz. The preservation of a substantial 2f₂ − f₁ DP suggested that it would be generated basal to the primary-tone place on the basilar membrane and there might be a reflection of the unique function of the remaining outer hair cells in the Bronx waltzer mice. These findings suggest that combination of ABR with DPOAE could offer useful information about differentiating the mechanism of hair cell dysfunction of the hereditary hearing impairment in the clinical fields.     

Normalization of poor auditory brainstem response in infants and children

In these past 10 years, the usefulness of auditory brainstem response (ABR) has been demonstrated in the clinical evaluation of audiological or neurological disorders, and the absence of an ABR is commonly accepted as consistent with a peripheral hearing loss caused by middle or inner ear diseases. In this article, the authors report nine infants and children who had an absent or difficult to detect ABR at the first examination with subsequent normalization of ABR. Repeated otological examinations were always normal in these patients. The final diagnoses were delayed development, Waardenburg syndrome with congenital heart disease and epilepsy, healthy infant, infantile convulsion, mental retardation with history of low birth weight, in each case, and chromosomal aberration in four patients. The reason for normalization of ABR in our patients is not clear and is yet to be ascertained. However, the authors believe that neurological maturation rather than an improved primary peripheral disorder is responsible for the noted normalization of the ABR, because of the high incidence of neurological abnormalities in these patients.     

A comparison of the three-dimensional auditory brainstem response and the conventional auditory brainstem response in children

For measurement of neural activity in the brainstem auditory pathway, the conventional two-dimensional (2D) auditory brainstem response (ABR) does not provide a true response, because the equivalent dipoles originate from the stereoregularity pathway. It is thus necessary to use three-dimensional (3D) ABR to estimate the true response of the brainstem. We recorded 3D ABR in a group of children and adults, and compared the results with those of the conventional 2D ABR.

The subjects were 22 children (age range 3–10 years) and 10 adults with no neurological disorders, and three patients: a boy and a girl who had experienced sudden brainstem dysfunction, and a girl who had sudden deafness. 3D ABR was recorded for all subjects, and the results were displayed on a computer screen for off-line analysis using an original 3D ABR analysis program.

Four leaf-like vector segments of 3D ABR existed during the first 8 ms after stimulation. Each vector segment corresponded to a peak of the conventional ABR, and showed the original directivity. The amplitudes of waves II and IV of the 3D ABR were significantly larger than those of the conventional ABR. 3D ABR was shown to be superior to the conventional ABR in obtaining absolute amplitude. We were able to clarify the development of brainstem function using 3D ABR. In one patient in whom only one wave was obtained, 3D ABR was able to identify the wave as wave V. These results indicate that ABR is useful both for identifying the kind of wave produced and for suggesting the wave origin.     

Pentobarbital-induced changes in the mouse brainstem auditory evoked potential as a function of click repetition rate and time postdrug

The effects of pentobarbital (80 mg/kg, i.p.) and saline injections on the BAEP were studied in 10 adult female BDF1 mice. Pentobarbital anesthesia induced statistically significant increases in the amplitudes and latencies of various BAEP components relative to preinjection and saline control values. These pentobarbital-induced changes were maximal shortly after drug administration and dissipated over time in a pattern similar to a drug elimination curve. Since pentobarbital and fast stimulus repetition rates are considered to be 'synaptic stressors', it was predicted that pentobarbital anesthesia and click repetition rate would have combined effects on the BAEP. This prediction was partially supported in that pentobarbital-induced changes in P4 amplitude and latency were significantly dependent on click repetition rate. The pentobarbital-induced effects on earlier BAEP components, however, proved to be largely independent of click rate. Pentobarbital-associated changes in the BAEP were not due to such factors as core temperature changes, circadian variations, and stress. The importance of anesthetic-induced changes in the BAEP for clinical and experimental studies is discussed.     

What subcortical-cortical relationships tell us about processing speech in noise

To advance our understanding of the biological basis of speech-in-noise perception, we investigated the effects of background noise on both subcortical- and cortical-evoked responses, and the relationships between them, in normal hearing young adults. The addition of background noise modulated subcortical and cortical response morphology. In noise, subcortical responses were later, smaller in amplitude and demonstrated decreased neural precision in encoding the speech sound. Cortical responses were also delayed by noise, yet the amplitudes of the major peaks (N1, P2) were affected differently, with N1 increasing and P2 decreasing. Relationships between neural measures and speech-in-noise ability were identified, with earlier subcortical responses, higher subcortical response fidelity and greater cortical N1 response magnitude all relating to better speech-in-noise perception. Furthermore, it was only with the addition of background noise that relationships between subcortical and cortical encoding of speech and the behavioral measures of speech in noise emerged. Results illustrate that human brainstem responses and N1 cortical response amplitude reflect coordinated processes with regards to the perception of speech in noise, thereby acting as a functional index of speech-in-noise perception.     

Temporal relationship between single unit activity in superior olivary complex and scalp-derived auditory brainstem response in guinea pig

Single unit activities in the region of the superior olivary complex were recorded from 8 guinea pigs concurrently with the recording of auditory brainstem potentials from the scalp. At any one anatomical site, be it a fiber tract (e.g. trapezoid body) or a nucleus (e.g. medial nucleus of the trapezoid body), the modal latency of the onset discharge of the units encountered corresponded in time with the latencies of several different waves (waves P2-P5) of the auditory brainstem response (ABR). Moreover, at the time of occurrence of just one of the ABR waves, single units in several diverse anatomical sites in and around the superior olive were found with modal latencies of onset discharge at that same time period. The slopes of the latency/intensity functions for both the peaks of the ABR and the modal latency of the onset discharge for most of the single units studied in the superior olive and its adjacent fiber tracts were remarkably similar. These data support the hypothesis of multiple rather than single generator site(s) for components of the ABR, at least, for waves P2-P5 in the guinea pig. These data do not distinguish whether the ABR are generated in part by travelling nerve action potentials or graded synaptic events.     

Binaural interaction effects on the auditory brainstem response of the cat and kitten

The auditory brainstem response (ABR) is a series of volume conducted potentials that can be recorded from the scalp within 10 ms following auditory stimulation. Differences between ABRs evoked with binaural stimulation and those constructed by summing equivalent numbers of monaural stimulation to each ear indicate the presence of binaural interaction for some ABR potentials but not for others. In the present study, ABR binaural interactions were studied in both cats and kittens. Binaural interactions were not seen for waves 1-3 but were present at the latencies of waves 4, 5 and, in most cases, 6. The sound intensities used were selected to insure that acoustic cross-over, i.e. sound presented monaurally to one ear stimulating the other, did not influence binaural interaction effects. Experiments with cats that had been monaurally deafened confirmed that the effects observed were not due to acoustic cross-over. Systematic manipulation of stimulus rate and intensity produced marked changes in the level of binaural interaction. Increases in stimulation rate from 10 to 100 clicks/s reduced binaural interaction for wave 4 and reversed the direction of binaural interaction for wave 5. Wave 6 was not generally present at rates above 10 clicks/s. Reduction of stimulus intensity reduced binaural interaction for wave 4. Binaural interaction effects were at adult levels in kittens of 20 days for waves 4 and 5. Wave 6 was not present until 30 days of age. These data suggest a possible model of the physiological processes producing binaural interaction which is based on occlusion as seen in other areas of the nervous system. In such a model, convergent input becomes more important in driving the generators of some ABR potentials when the system is stressed (as, for example, by increased stimulus rate), than it is when the system is not stressed.     

Coordinated plasticity in brainstem and auditory cortex contributes to enhanced categorical speech perception in musicians

Musicianship is associated with neuroplastic changes in brainstem and cortical structures, as well as improved acuity for behaviorally relevant sounds including speech. However, further advance in the field depends on characterizing how neuroplastic changes in brainstem and cortical speech processing relate to one another and to speech‐listening behaviors. Here, we show that subcortical and cortical neural plasticity interact to yield the linguistic advantages observed with musicianship. We compared brainstem and cortical neuroelectric responses elicited by a series of vowels that differed along a categorical speech continuum in amateur musicians and non‐musicians. Musicians obtained steeper identification functions and classified speech sounds more rapidly than non‐musicians. Behavioral advantages coincided with more robust and temporally coherent brainstem phase‐locking to salient speech cues (voice pitch and formant information) coupled with increased amplitude in cortical‐evoked responses, implying an overall enhancement in the nervous system's responsiveness to speech. Musicians' subcortical and cortical neural enhancements (but not behavioral measures) were correlated with their years of formal music training. Associations between multi‐level neural responses were also stronger in musically trained listeners, and were better predictors of speech perception than in non‐musicians. Results suggest that musicianship modulates speech representations at multiple tiers of the auditory pathway, and strengthens the correspondence of processing between subcortical and cortical areas to allow neural activity to carry more behaviorally relevant information. We infer that musicians have a refined hierarchy of internalized representations for auditory objects at both pre‐attentive and attentive levels that supplies more faithful phonemic templates to decision mechanisms governing linguistic operations.     

A study of adaptation mechanisms based on ABR recorded at high stimulation rate

ObjectiveThis paper analyzes the fast and slow mechanisms of adaptation through a study of latencies and amplitudes on ABR recorded at high stimulation rates using the randomized stimulation and averaging (RSA) technique.MethodsThe RSA technique allows a separate processing of auditory responses, and is used, in this study, to categorize responses according to the interstimulus interval (ISI) of their preceding stimulus. The fast and slow mechanisms of adaptation are analyzed by the separated responses methodology, whose underlying principles and mathematical basis are described in detail.ResultsThe morphology of the ABR is influenced by both fast and slow mechanisms of adaptation. These results are consistent with previous animal studies based on spike rate.ConclusionsBoth fast and slow mechanisms of adaptation are present in all subjects. In addition, the distribution of the jitter and the sequencing of the stimuli may be critical parameters when obtaining reliable ABRs.SignificanceThe separated responses methodology enables for the first time the analysis of the fast and slow mechanisms of adaptation in ABR obtained at stimulation rates greater than 100 Hz. The non-invasive nature of this methodology is appropriate for its use in humans.     

Effects of Background Noise on Cortical Encoding of Speech in Autism Spectrum Disorders

This study provides new evidence of deficient auditory cortical processing of speech in noise in autism spectrum disorders (ASD). Speech-evoked responses (~100–300 ms) in quiet and background noise were evaluated in typically-developing (TD) children and children with ASD. ASD responses showed delayed timing (both conditions) and reduced amplitudes (quiet) compared to TD responses. As expected, TD responses in noise were delayed and reduced compared to quiet responses. However, minimal quiet-to-noise response differences were found in children with ASD, presumably because quiet responses were already severely degraded. Moreover, ASD quiet responses resembled TD noise responses, implying that children with ASD process speech in quiet only as well as TD children do in background noise.     

听性脑干反应和纯音听阈在听神经瘤早期诊断中的应用

目的 探讨采用听性脑干反应和纯音听阈对早期诊断听神经瘤的临床应用价值.方法 回顾性分析了111例听神经瘤患者的临床资料、纯音听阈、听性脑干反应及增强磁共振结果,采用线性回归分析纯音听阈均值与肿瘤体积、病程是否存在相关性,采用卡方检验分析不同肿瘤体积在听性脑干反应异常发生率上是否存在差异.结果 听神经瘤引起感音神经性耳聋,纯音听阈均值与病程存在显著地相关性(P=0.000);听性脑干反应诊断听神经瘤的敏感度和特异度分别为98.2％和93.6％,肿瘤最大径＞3 cm与≤3 cm两组,在患侧和对侧Ⅲ～Ⅳ波间期异常发生率上,差异均具有统计学意义(P值分别为0.038和0.045).结论 听性脑干反应联合纯音测听是早期诊断听神经瘤的有效方法.     

Lesch-Nyhan syndrome with delayed onset of self-mutilation: hyperactivity of interneurons at the brainstem and blink reflex

We studied a case of Lesch-Nyhan syndrome with delayed onset of self-mutilation. Athetotic cerebral palsy and mental retardation were diagnosed at 1 year old, but the disease was not suspected until age 8 years when he began biting his lips and fingers. There was no obvious alteration of catecholamine in urine and CSF. We attempted to induce a series of blink reflexes by electric, mechanical and photic procedures. The R1 amplitude increased and the latency of the R2 shortened compared with controls. This shows that not only orbicularis motoneuron itself, but also uncrossed interneurons, are in a state of hyperexcitability. The contralateral R2 was poor which was in favour of hypoexcitability of the crossed interneurons at the brainstem. The significant large response was obtained by photic procedure which was in favour of hyperexcitability of the motoneurons. Therefore, it is demonstrated that a thorough examination of blink reflexes provides a useful method for examination of a state of the underlying neural activity.     

Newborn brain event-related potentials revealing atypical processing of sound frequency and the subsequent association with later literacy skills in children with familial dyslexia

The role played by an auditory-processing deficit in dyslexia has been debated for several decades. In a longitudinal study using brain event-related potentials (ERPs) we investigated 1) whether dyslexic children with familial risk background would show atypical pitch processing from birth and 2) how these newborn ERPs later relate to these same children’s pre-reading cognitive skills and literacy outcomes. Auditory ERPs were measured at birth for tones varying in pitch and presented in an oddball paradigm (1100 Hz, 12%, and 1000 Hz, 88%). The brain responses of the typically reading control group children (TRC group, N = 25) showed clear differentiation between the frequencies, while those of the group of reading disability with familial risk (RDFR, 8 children) and the group of typical readers with familial risk (TRFR, 14 children) did not differentiate between the tones. The ERPs of the latter two groups differed from those of the TRC group. However, the two risk groups also showed a differential hemispheric ERP pattern. Furthermore, newborn ERPs reflecting passive change detection were associated with phonological skills and letter knowledge prior to school age and with phoneme duration perception, reading speed (RS) and spelling accuracy in the 2nd grade of school. The early obligatory response was associated with more general pre-school language skills, as well as with RS and reading accuracy (RA). Results suggest that a proportion of dyslexic readers with familial risk background are affected by atypical auditory processing. This is already present at birth and also relates to pre-reading phonological processing and speech perception. These early differences in auditory processing could later affect phonological representations and reading development. However, atypical auditory processing is unlikely to suffice as a sole explanation for dyslexia but rather as one risk factor, dependent on the genetic profile of the child.     

Effects of neonatal hypoxic-ischemic brain injury on skilled motor tasks and brainstem function in adult rats

In an attempt to establish more sensitive long-term neurofunctional measurements for neonatal hypoxic-ischemic brain injury, we examined skilled motor task and brainstem functions in adult rats after neonatal cerebral hypoxia-ischemia (H-I), using a staircase test and auditory brainstem response (ABR), respectively. Seven-day-old rats underwent a combination of left common carotid artery ligation and exposure to 8% O(2) for 1 h (n=16). The control animals only received sham operation (n=16). At 3 months of age, the staircase test and ABR were performed. In the staircase test, H-I animals showed marked impairment of skilled forelimb use in the side contralateral to the occluded artery, and the degree of brain damage correlated significantly to skilled forelimb use. In the ABR, H-I animals showed brainstem dysfunction assessed by measuring interpeak latencies for waves III-V and I-V. We also examined the brainstem with antibodies specific for activated caspase-3, a protein involved in initiation of apoptosis, and observed that caspase-3 was activated in the ipsilateral inferior colliculus at 24 h after H-I. The present study shows that both the staircase test and ABR are sensitive and objective long-term neurofunctional measurements that can be used in future studies to assess therapeutic intervention in this neonatal cerebral H-I model.     

Acute and long-term effects of adrenocorticotropin and dexamethasone on the auditory brainstem response in multiple sclerosis patients

Auditory brain-stem responses (ABRs) were compared in two groups of multiple sclerosis (MS) patients receiving standard treatment with adrenocorticotropin (ACTH) and with dexamethasone (DEX). ABRs were recorded prior to treatment, on the lst and 8th day of therapy, and 21 days after the hormonal treatment had been discontinued. ABRs in MS patients were within the normal range of variability. Latencies of ABR components increased with increasing rate of presentation, and with decreasing intensity of the click stimuli. Changes in ABRs displayed a consistent pattern in patients treated with ACTH, but showed less coherence after DEX. In ACTH treated patients' latencies of the late ABR waves V and V_n were prolonged after clicks of high intensity, and reduced following clicks of low intensity resulting in a decreased slope of the latency-intensity function of these ABR waves. This pattern became most prominent in the recordings after the treatment had been discontinued, and could reflect an improved transmission across both afferent excitatory and recurrent inhibitory synapses in the auditory pathways. The findings indicate that — besides a common anti-inflammatory action — therapies with ACTH and DEX differ with regard to their influence on central nervous functioning.     

Modulating calbindin and parvalbumin immunoreactivity in the cochlear nucleus by moderate noise exposure in mice.: A quantitative study on the dorsal and posteroventral cochlear nucleus

The number of calbindin D-28k and parvalbumin immunoreactive (IR) neurons were characterized on sections from the cochlear nucleus, dorsal cochlear nucleus (DCN) and posteroventral cochlear nucleus (PVCN) using two-dimensional quantification. After noise exposure (6–12 kHz, 2 h, at either 80 dB SPL or 103 dB SPL), the number of calbindin and parvalbumin immunoreactive neurons increased in CBA/CBA mice. Quantitative analysis of calbindin-IR in the PVCN did not show a statistically significant difference between any of the groups, whereas statistically significant differences in calbindin-IR were found in the DCN for the 103 dB and 80 dB group compared to the control group, and 103 dB compared to the 80 dB group, respectively. A statistically significant increase in the number of parvalbumin-IR neurons in the PVCN and the DCN was evident in the 103 dB and 80 dB group compared to the control group, and in the 103 dB compared to the 80 dB group. The data indicate that increasing sound stimulation causes a graded increase in the expression of calcium-binding protein immunoreactivity in the DCN and PVCN neurons and neuropil. This increase of protein expression is due to increased positive immunoreactivity in `silent' neurons. These findings implicate that these neurons have the possibility to react against trauma and display calbindin or parvalbumin as a rescue event. The ability to map sound-induced calcium-binding protein changes in auditory neurons may be useful in future studies designed for detecting early patterns of neurodegeneration and neuroprotection in the central auditory pathway.     

The effects of stress and statistical cues on continuous speech segmentation: an event-related brain potential study

The study of the processes involved in speech segmentation has gained special relevance in recent years by trying to establish what type of information listeners use to segment the speech signal into words. An event-related brain potential experiment was conducted in order to understand how two of these cues (statistical and stress cues) interact. The experiment consisted of the presentation of artificial speech streams in which words were marked either by statistical cues alone, or by a combination of statistical and stress cues. As a baseline, comparison streams were also created with the same syllables but organized in random order. Results showed an N400 component that marks the on-line segmentation of speech into words, and an increased positivity (P2 component) for languages that include both types of cues. Possible implications of these results for the process of speech segmentation are discussed.     

Exploring the relation between brain response to speech at 6-months and language outcomes at 24-months in infants at high and low risk for autism spectrum disorder: A preliminary functional near-infrared spectroscopy study

Infants at high familial risk for autism spectrum disorder (ASD) are at increased risk for language impairments. Studies have demonstrated that atypical brain response to speech is related to language impairments in this population, but few have examined this relation longitudinally. We used functional near-infrared spectroscopy (fNIRS) to investigate the neural correlates of speech processing in 6-month-old infants at high (HRA) and low risk (LRA) for autism. We also assessed the relation between brain response to speech at 6-months and verbal developmental quotient (VDQ) scores at 24-months. LRA infants exhibited greater brain response to speech in bilateral anterior regions of interest (ROIs) compared to posterior ROIs, while HRA infants exhibited similar brain response across all ROIs. Compared to LRA infants, HRA+ infants who were later diagnosed with ASD had reduced brain response in bilateral anterior ROIs, while HRA- infants who were not later diagnosed with ASD had increased brain response in right posterior ROI. Greater brain response in left anterior ROI predicted VDQ scores for LRA infants only. Findings highlight the importance of studying HRA+ and HRA- infants separately, and implicate a different, more distributed neural system for speech processing in HRA infants that is not related to language functioning.