Search

Objective The purpose of this study is to expand our understanding of how the human auditory brainstem encodes temporal and spectral acoustic cues in voiced stop consonant–vowel syllables. Methods Auditory evoked potentials measuring activity from the brainstem of 22 normal learning children were recorded to the voiced stop consonant syllables [ga], [da], and [ba]. Spectrotemporal information distinguishing these voiced consonant–vowel syllables is contained within the first few milliseconds of the burst and the formant transition to the vowel. Responses were compared across stimuli with respect to their temporal and spectral content. Results Brainstem response latencies change in a predictable manner in response to systematic alterations in a speech syllable indicating that the distinguishing acoustic cues are represented by neural response timing (synchrony). Spectral analyses of the responses show frequency distribution differences across stimuli (some of which appear to represent acoustic characteristics created by difference tones of the stimulus formants) indicating that neural phase-locking is also important for encoding these acoustic elements. Conclusions Considered within the context of existing knowledge of brainstem encoding of speech–sound structure, these data are the beginning of a comprehensive delineation of how the human auditory brainstem encodes perceptually critical features of speech. Significance The results of this study could be used to determine how neural encoding is disrupted in the clinical populations for whom stop consonants pose particular perceptual challenges (e.g., hearing impaired individuals and poor readers).

Temporal integration was measured at a relatively low and a relatively high signal frequency under conditions of off-frequency masking. The masker was typically gated for 300 ms, and the signal was presented 70 ms after masker onset. In experiment 1, the signal frequency was 500 or 2000 Hz. Temporal integration was measured in quiet and in the presence of a masker whose frequency was lower or higher than the signal frequency. In all listening situations, there was less integration at 2000 Hz than at 500 Hz. This effect of frequency was particularly dramatic in the presence of a lower frequency masker, where there was almost no integration at 2000 Hz. Experiment 2 showed that this dramatic effect of frequency cannot be understood in terms of the underlying psychometric functions. Experiment 3 measured temporal integration at 750 and 2000 Hz for a large number of masker-signal frequency separations for both a tonal and a noise masker, and in conditions where the masker was gated or continuous. The results with the gated tonal masker largely confirmed the results of experiment 1. The results with the continuous tonal masker and the gated or continuous noise masker, however, were quite different. In those cases, the amount of temporal integration at both signal frequencies was more or less independent of the masker-signal separation; the masked temporal integration was nearly equal to the integration in quiet. Thus based on the conditions evaluated here, off-frequency masked temporal integration differs substantially from integration in quiet only for gated tonal maskers located considerably lower in frequency than the signal. It is unclear how to account for this finding, although it may be related to attentional factors.

Subcellular localization of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds has been examined only in the liver. The objective of this study was (1) to examine and compare the subcellular distribution of TCDD within hepatic and nonhepatic (lungs/kidneys) tissues of female Sprague–Dawley rats acutely exposed to TCDD, (2) to analyze species comparisons in the subcellular localization of TCDD in multiple tissues, (3) to investigate the effect of dose on subcellular distribution of TCDD, (4) to analyze the effect of subchronic exposure on the subcellular distribution of TCDD, and (5) to examine one possible mechanism for subcellular localization of TCDD. Female Sprague–Dawley rats and B6C3F1 mice received a single oral dose of 0.1, 1.0, or 10 μg [3H]TCDD/kg body weight and subcellular fractions of the liver, lungs, and kidneys were prepared by differential centrifugation 3 days after exposure. Analysis of the rat subcellular fractions revealed that TCDD was equally distributed between the hepatic P9 (mitochondrial, lysosomal, and nuclear) and S9 (cytosol and microsomal) fractions at all doses tested. In contrast, TCDD was concentrated in the P9 of rat nonhepatic tissues at all doses studied. Differential centrifugation of the hepatic S9 showed that TCDD was localized within the hepatic P100 (microsomal) fraction at all doses tested. In contrast, TCDD localized in pulmonary and renal S100 (cytosolic) fractions at all doses. The subcellular distribution of TCDD in the liver and lungs of acutely exposed B6C3F1 mice was similar to that observed in the rats. Although TCDD was concentrated within the renal P9, the remainder of TCDD in the S9 was evenly distributed between the S100 and the P100 fractions of acutely exposed B6C3F1 mice. Subchronic exposure of B6C3F1 mice to 1.5 or 150 ng [3H]TCDD/kg/day revealed that increasing dose resulted in equal distribution of TCDD between the hepatic S9 and P9 versus concentration in the renal P9. In addition, a dose-dependent increase in accumulation of TCDD in the hepatic P100 was accompanied by a dose-dependent increase in TCDD localization in the renal S100 of mice subchronically exposed to TCDD. TCDD exposure in rats resulted in a dose-dependent increase in the induction of CYP1A1 protein and associated enzyme activity in hepatic, pulmonary, and renal microsomes. TCDD-induced CYP1A2 protein levels and associated enzymatic activity were only present in hepatic microsomes. This is the first report to suggest that subcellular distribution of TCDD differs between hepatic and nonhepatic tissues and demonstrate that the liver-specific microsomal localization of TCDD in female Sprague–Dawley rats also occurs in the liver of female B6C3F1 mice acutely or subchronically exposed to TCDD. In addition, these data are consistent with the hypothesis that the hepatic sequestration of TCDD is due to an interaction with CYP1A2. Furthermore, the lack of pulmonary/renal sequestration coupled with the lack of localization of TCDD in pulmonary/renal microsomes also supports the role of CYP1A2 as a hepatic microsomal binding protein involved in TCDD sequestration..

Development of the human auditory brainstem is thought to be primarily complete by the age of ∼2 years, such that subsequent sensory plasticity is confined primarily to the cortex. However, recent findings have revealed experience-dependent developmental plasticity in the mammalian auditory brainstem in an animal model. It is not known whether the human system demonstrates similar changes and whether experience with sounds composed of acoustic elements relevant to speech may alter brainstem response characteristics. We recorded brainstem responses evoked by both click and speech syllables in children between the ages of 3 and 12 years. Here, we report a neural response discrepancy in brainstem encoding of these two sounds, observed in 3- to 4-year-old children but not in school-age children. Whereas all children exhibited identical neural activity to a click, 3- to 4-year-old children displayed delayed and less synchronous onset and sustained neural response activity when elicited by speech compared with 5- to 12-year-olds. These results suggest that the human auditory system exhibits developmental plasticity, in both frequency and time domains, for sounds that are composed of acoustic elements relevant to speech. The findings are interpreted within the contexts of stimulus-related differences and experience-dependent plasticity.

Children with language-based learning problems often exhibit pronounced speech perception difficulties. Specifically, these children have increased difficulty separating brief sounds occurring in rapid succession (temporal resolution). The purpose of this study was to better understand the consequences of auditory temporal resolution deficits from the perspective of the neural encoding of speech. The findings provide evidence that sensory processes relevant to cognition take place at much earlier levels than traditionally believed. Thresholds from a psychophysical backward masking task were used to divide children into groups with good and poor temporal resolution. Speech-evoked brainstem responses were analyzed across groups to measure the neural integrity of stimulus-time mechanisms. Results suggest that children with poor temporal resolution do not have an overall neural processing deficit, but rather a deficit specific to the encoding of certain acoustic cues in speech. Speech understanding relies on the ability to attach meaning to rapidly fluctuating changes of both the temporal and spectral information found in consonants and vowels. For this to happen properly, the auditory system must first accurately encode these time-varying acoustic cues. Speech perception difficulties that often co-occur in children with poor temporal resolution may originate as a neural encoding deficit in structures as early as the auditory brainstem. Thus, speech-evoked brainstem responses are a biological marker for auditory temporal processing ability.

The auditory brain stem response to speech mimics the acoustic characteristics of the speech signal with remarkable fidelity. This makes it possible to derive from it considerable theoretical and clinically applicable information relevant to auditory processing of complex stimuli. Years of research have led to the current characterization of these neural events with respect to the underlying acoustic information they reflect. The majority of data reviewed here originates from studies using a /da/ syllable to elicit the brain stem response, which consists of transient and periodic (frequency following) neural activity. We describe how the human auditory brain stem response separately encodes source and filter characteristics of the acoustic signal, which reflects paralinguistic and linguistic information simultaneously conveyed in speech. In normal-hearing individuals, these two classes of response components (source and filter) are highly correlated within a class but not between classes. This response dissociation becomes pronounced when stimuli are presented in background noise or with faster stimulus rates. In addition, some learning-impaired children show a selective deficiency in the neural encoding of acoustic features associated with the filter characteristics of speech. These children show no deficits in the encoding of source components, further supporting the notion of separate neural mechanisms. Overall, the auditory brain stem response to speech provides a way to access subcortical auditory processing mechanisms and may be used as a biological marker of deficient sound encoding associated with learning and auditory processing disorders.

The physiological mechanisms that contribute to abnormal encoding of speech in children with learning problems are yet to be well understood. Furthermore, speech perception problems appear to be particularly exacerbated by background noise in this population. This study compared speech-evoked cortical responses recorded in a noisy background to those recorded in quiet in normal children (NL) and children with learning problems (LP). Timing differences between responses recorded in quiet and in background noise were assessed by cross-correlating the responses with each other. Overall response magnitude was measured with root-mean-square (RMS) amplitude. Cross-correlation scores indicated that 23% of LP children exhibited cortical neural timing abnormalities such that their neurophysiological representation of speech sounds became distorted in the presence of background noise. The latency of the N2 response in noise was isolated as being the root of this distortion. RMS amplitudes in these children did not differ from NL children, indicating that this result was not due to a difference in response magnitude. LP children who participated in a commercial auditory training program and exhibited improved cortical timing also showed improvements in phonological perception. Consequently, auditory pathway timing deficits can be objectively observed in LP children, and auditory training can diminish these deficits.

Previous studies showed exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) enhances the development of endometriotic lesions. In this study we examined the effects of other polyhalogenated aromatic hydrocarbons on endometriotic proliferation. B6C3F1 female mice were treated via oral gavage a total of five times, with 3 weeks between each dosing, with 0, 1, 3, or 10 micrograms 2,3,7,8,-TCDD/kg body weight (bw); 3 or 30 mg 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153)/kg bw; 100, 300, or 1000 micrograms 3,3',4,4',5-pentachlorobiphenyl (PCB 126)/kg bw; 10, 30, or 100 micrograms 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF)/kg bw; or 2 or 20 mg 1,3,6,8-TCDD/kg at 10 ml/kg bw. Endometriosis was surgically induced during the week of the second dosing. Three weeks following the final dose, the mice were euthanized and endometriotic lesions, whole body, liver, ovaries, uterine horn, and thymus were weighted, and lesion diameters were measured. Lesions, uterine horns, and ovaries were fixed for histopathology and livers were processed for measurement of ethoxyresorufin O-deethylase (EROD) activity. Both 2,3,7,8-TCDD (1 and 3 micrograms/kg bw) and 4-PeCDF (100 micrograms/kg bw) significantly enhanced the growth of endometrial lesions. No statistically significant increase in endometriotic lesion size was detected in animals treated with either PCB 126 or with the highest dose of 2,3,7,8-TCDD, possibly due to the effects of histologically observed ovarian toxicity. The nondioxin-like compounds, PCB 153 and 1,3,6,8-TCDD, produced no observable effects on endometriosis. Hepatic EROD activity was significantly induced by 2,3,7,8-TCDD, 4-PeCDF, and PCB 126, but not by PCB 153 or 1,3,6,8-TCDD. The results of this study provide preliminary support for the hypothesis that halogenated aromatic hydrocarbon-promoted endometriosis may be Ah receptor mediated.