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Biomedical subjects

N Kraus

Publications and source records attributed to N Kraus.

At least 55 records · Page 3Linked to original sources

Clinical implications of primary and nonprimary pathway contributions to the middle latency response generating system.

Clinical use of the middle latency response (MLR) has been limited by the variability of the response during sleep in young children. Theoretically, this variability can be explained by the differential maturation of the primary and nonprimary components of the MLR generating system. The model is supported by animal neurophysiological data. Applied to the human system, the model predicts that, in children, MLR generators are active only during certain stages of sleep. From a clinical standpoint, this has led to a procedure for signaling the clinician when a child is in a sleep state favorable for recording the MLR.

Acoustic Stimulation↗

Improving the reliability of the auditory middle latency response by monitoring EEG delta activity.

The auditory middle latency response (MLR), a useful tool in the assessment of low-frequency auditory sensitivity, can be consistently recorded in young children during wakefulness, stages 1 and 2, and REM sleep. Responses are often absent or questionable during stage 4. An on-line measure indicating favorable periods for recording MLR during sleep is important for interpretation of absent potentials. Here, for children 5 to 7 years old, the reliability and detectability of MLR was compared to sleep state and the dominance of delta activity (0-3 Hz) in the EEG frequency spectrum. Dominance of delta activity, a characteristic of stage 4, was expressed in a "delta ratio," a measure of relative EEG energy in the 0 to 3 Hz frequency spectrum. A fixed delta ratio (DR = 9) allowed the differentiation of periods favorable for MLR. MLR wave Pa amplitude and latency also varied with delta ratio. Results indicate that on-line monitoring of the delta ratio will allow reliable testing of MLR in clinical situations.

Acoustic Stimulation↗

Mismatch negativity in the neurophysiologic/behavioral evaluation of auditory processing deficits: a case study.

The subject of this case report is an 18-year-old woman with grossly abnormal auditory brain stem response (ABR), normal peripheral hearing, and specific behavioral auditory processing deficits. Auditory middle latency responses (MLRs) and cortical potentials N1, P2, and P300 were intact. The mismatch negativity (MMN) was normal in response to certain synthesized speech stimuli and impaired to others--consistent with her behavioral discrimination of these stimuli. Behavioral tests of auditory processing were consistent with auditory brain stem dysfunction. A neuropsychological evaluation revealed normal intellectual and academic performance. The subject was in her first year of college at the time of the evaluation. This case study is important because: (1) Although there have been several reports of absent/abnormal ABR with preserved peripheral hearing and deficits in auditory processing, little is known about the specific nature of the auditory deficits experienced by these individuals. Such information may be valuable to the clinical management of patients with this constellation of findings. (2) Of interest is the information that the mismatch negativity (MMN) cortical event-related potential can bring to the evaluation of patients with auditory processing deficits. The MMN reflects central auditory processing of small acoustic differences and may provide an objective measure of auditory discrimination. (3) From a theorectical standpoint, a patient with neural deficits affecting specific components of the auditory pathway provides insight into the relationship between evoked potentials and physiological mechanisms of auditory processing. How do various components of the auditory pathway contribute to speech discrimination? How might evoked potentials reflect the processes underlying the neural coding of specific features of speech stimuli such as timing and spectral cues?

Achievement↗

Speech-evoked cortical potentials in children.

Event-related potentials (ERPs) were obtained to synthesized speech stimuli in 16 school-aged children (7-11 years) and compared to responses in 10 adults. P1, N1, and P2 event-related potentials were elicited by the phoneme /ga/. The mismatch negativity (MMN) was elicited by variants of /da/ and /ga/, which differ in the onset frequency of the second and third formant transitions. In general, the well-defined N1/P2 complex characteristic of the adult response, was not found in children. Waves P1 and N1 had longer peak latencies in children than in adults. Wave P2 amplitude was smaller in children than in adults. In contrast to the often poorly delineated earlier cortical potentials, the MMN was well defined in children. Significant MMNs were obtained in all subjects tested. MMN magnitude (peak amplitude and area) was significantly larger in the children. No significant differences were found in peak latency and duration of the MMN in children compared to the adult response. Another negative wave occurring at 400 msec was also observed in response to the deviant stimuli. This negative wave occurred at a similar latency in adults and children and was significantly larger and more robust in children. Results support the view that development of ERPs does not involve a hierarchical process with respect to latency. That is, earlier occurring waves do not necessarily mature before later occurring waves. The latencies of P1, N1, and P2 and overall morphology of these waves may provide a measure of maturation of central pathways. The early development of the MMN, its apparent robustness in school-aged children, and its reflection of the processing of acoustic differences in speech stimuli suggest its possible use in the assessment of central auditory function.

Acoustic Stimulation↗

Reticular formation influences on primary and non-primary auditory pathways as reflected by the middle latency response.

Ongoing studies are aimed at identifying the neural pathways responsible for the middle latency response (MLR). These studies involve the analysis of surface and intracranial potentials following pharmacologic inactivation (with lidocaine) of discrete regions of the guinea pig brain. Previous investigations have shown that MLR surface waves recorded over the temporal lobe originate from pathways anatomically and functionally distinct from those that generate MLR waves recorded over the midline, and that both primary and non-primary auditory thalamo-cortical pathways contribute to the guinea pig MLR. The present investigation examines the role of the mesencephalic reticular formation (mRF) in the MLR generating system. Inactivation of the mRF was associated with disruption of the midline response. These waves have been shown to reflect activity from non-primary subdivisions of the thalamo-cortical pathway. Components recorded over the temporal lobe were also affected, consisting of amplitude reduction and latency prolongation without changes in response morphology. Changes in temporal MLR components with mRF inactivation were smaller than those associated with direct inactivation of primary and non-primary subdivisions of the medial geniculate body. These findings indicate that mRF input is essential for normal generation of those components of the MLR thought to reflect both primary and non-primary auditory pathway activity.

Animals↗

Contributions of medial geniculate body subdivisions to the middle latency response.

Ongoing studies in our laboratory, concerned with identifying the neural pathways responsible for the auditory middle latency response (MLR), have involved analysis of surface and intracranial potentials following pharmacologic inactivation (with lidocaine) of small regions in the guinea pig brain. Previous studies indicate that MLR surface waves recorded over the temporal lobe originate from pathways anatomically distinct from those that generate MLR waves recorded over the midline. The medial geniculate body (MG) contributes to both MLR responses. At issue here are the relative contributions of ventral and caudomedial subdivisions, which have been linked to primary and non-primary auditory pathways, respectively. Ventral and caudomedial subdivisions contributed to the surface-recorded MLR in a distinctive manner. Lidocaine injections to both areas reduced the amplitude of the surface temporal response. Caudomedial injections had a much greater effect on the surface midline responses than did injections in the ventral portion. Thus, the ventral division, a part of the primary auditory pathway, contributes chiefly to the temporal response. The caudomedial portion, which may be linked to non-primary auditory pathways, contributes to both responses.

Acoustic Stimulation↗

Mismatch negativity event-related potential elicited by speech stimuli.

The mismatch negativity (MMN) is a passively elicited event-related potential that is extremely sensitive to acoustic stimulus properties. The MMN was characterized in normal adults and school-age children in response to speech stimuli differing minimally in the onset frequency of the second and third formant transitions. The speech-evoked MMN consists of a negative waveform at about 230 msec that occurs in response to the deviant stimulus when it is presented in an oddball paradigm. It is absent in response to that same stimulus when presented alone. The MMN was clearly present in all adults and children tested. Using the procedures developed in this study, this event-related potential was found to be robust enough in individual subjects to be considered a potential clinical measure for assessing central auditory function in school-age children and adults.

Adolescent↗

Absence of sensorineural hearing loss in treated infants and children with congenital toxoplasmosis.

Educationally significant hearing loss has been reported in 10% to 15% of children with congenital toxoplasmosis. As part of a pilot study to assess feasibility and safety of prolonged therapy for congenital toxoplasmosis, 30 congenitally infected infants and children were evaluated for auditory function. Serial testing, beginning within 2 months of birth, was performed. Availability of auditory brainstem response (ABR) testing made evaluation at an earlier age than previously possible. Six (20%) of the 30 infants had mild to moderate conductive type hearing loss associated with otitis media. No infant or child had sensorineural hearing loss. The better outcome we observed compared to previous reports of a 15% to 26% incidence of sensorineural hearing loss and 10% to 15% incidence of educationally significant, bilateral hearing impairment may be related to early initiation and/or prolonged institution of antimicrobial therapy. Continued followup to exclude progressive hearing impairment and study of larger numbers of children are needed to verify these preliminary findings.

Audiometry, Evoked Response↗

Subcortical and cortical components of the MLR generating system.

The contributions of the auditory thalamo-cortical pathway, mesencephalic reticular formation, and inferior colliculus to the surface recorded auditory middle latency response (MLR) were assessed by selective inactivation of these areas with lidocaine. Evoked responses were recorded simultaneously from these areas and from the cortical surface. Lidocaine-induced changes were compared across recording sites. In the guinea pig, surface components measured from over the temporal lobe (waves A, B and C) and the midline (waves M- and M+) have been previously shown to reflect the activity of two distinct generating mechanisms. Effects of lidocaine injections corresponded to selective changes in components from these two systems. Injections in the medial geniculate body (MGB) were associated with total disruption of surface potentials measured over the temporal lobe, auditory cortex (AC) responses, and local activity in MGB. Thus the thalamo-cortical pathway appears to be important for the generation of MLRs recorded from the surface of the temporal lobe. These injections generally did not alter the surface midline responses or activity obtained from either the mesencephalic reticular formation (mRF) or the inferior colliculus (IC). Lidocaine injections within AC did not alter the basic response morphology of surface potentials, nor were significant changes measured within AC. Lidocaine injections into the mRF produced changes in all surface temporal potentials, the M+ midline surface potential, and in local potentials recorded from MGB and mRF. Injections into the IC changed surface and subcortical responses at all sites. This was the only injection to affect activity at the latency of surface midline wave, M-1. This wave may be the animal analogue for human wave Na. Control experiments indicated that the effects observed were specific to the neural inactivation of target areas. The MLR generating system appears to consist of contributions and interactions from multiple areas including the auditory thalamo-cortical pathway, mRF and IC. The animal model and experimental strategy described appear promising for linking the contributions from specific brain areas to surface MLR waves.

Animals↗

Perceived risk, stigma, and potential economic impacts of a high-level nuclear waste repository in Nevada.

This study investigates the potential impacts of the proposed nuclear waste repository at Yucca Mountain, Nevada, upon tourism, retirement and job-related migration, and business development in Las Vegas and the state. Adverse impacts may be expected to result from perceptions of risk, stigmatization, and socially amplified reactions to "unfortunate events" associated with the repository (major and minor accidents, discoveries of radiation releases, evidence of mismanagement, attempts to sabotage or disrupt the facility, etc.). The conceptual underpinnings of risk perception, stigmatization, and social amplification are discussed and empirical data are presented to demonstrate how nuclear images associated with Las Vegas and the State of Nevada might trigger adverse economic effects. The possibility that intense negative imagery associated with the repository may cause significant harm to Nevada's economy can no longer be ignored by serious attempts to assess the risks and impacts of this unique facility. The behavioral processes described here appear relevant as well to the social impact assessment of any proposed facility that produces, uses, transports, or disposes of hazardous materials.

Humans↗

Clinical applications of the middle latency response.

The protocol developed in our laboratory for the assessment of hearing, involving the middle latency response (MLR), is described. Applications are illustrated in cases: (1) where the MLR was used to identify residual low frequency hearing and (2) where the MLR provided the only available threshold data because brainstem damage compromised the use of the ABR for hearing assessment. An understanding of the MLR generating system can provide insight into the mechanisms responsible for the inconsistency of the MLR in children. Animal models and human data indicate that maturation of the generating network may involve an early developing, variable system influenced by the mesencephalic reticular formation, and a later developing, stable system dominated by the thalamo-cortical pathway. If the thalamo-cortical system is not yet mature, one might expect the response to vary depending upon the subject's level of alertness. The observed MLR may then be dominated by other, sleep-dependent systems involving the reticular formation.

Animals↗

MLRs in children are consistently present during wakefulness, stage 1, and REM sleep.

Auditory middle latency responses (MLRs) were recorded continuously from normal children, ages 4 to 9 years, during natural sleep. Concurrently obtained EEG recordings were used to determine stages of sleep. Wave Pa was consistently present during wakefulness, alpha, stage 1, and REM sleep. Wave Pa detectability was poor during stage 4 sleep. The probability of obtaining wave Pa during stage 4 increased systematically with age. During stages 2 and 3, Pa detectability was variable. The inconsistency of MLRs in children currently limits their clinical use. These data indicate that the occurrence of MLRs in children is not haphazard, and that the MLR in children can be reliably obtained during certain states of arousal. A straightforward clinical application of these findings is that efforts to obtain MLRs be concentrated during periods favorable for recording the response. We suggest practical strategies for detecting optimal sleep stages.

Auditory Perception↗

Multichannel intracranial recording device using a color imaging brain mapping system.

A procedure is described for the manufacture and use of a multichannel (up to 20) intracranial recording device. Electrodes are arranged in a horizontal plane, and can be controlled by a conventional microdrive. Data from multiple channels are visualized and analyzed utilizing a commercially available color imaging brain mapping system. Potential research applications include studies of neural generators of evoked responses through the simultaneous recording of intracranial and scalp potentials.

Animals↗

Midline and temporal lobe MLRs in the guinea pig originate from different generator systems: a conceptual framework for new and existing data.

In the guinea pig and gerbil, individual components within the MLR time frame differ in optimal recording location. Specifically, MLR components obtained from the midline differ from those obtained over the temporal lobe. In the present paper midline and temporal lobe components were shown to differ not only in scalp topography but also in response to the following experimental manipulations: intracortical injection of neural inactivating agents (lidocaine and kainic acid), temporal lobe ablation, electrolytic lesions, systemic anesthesia, stimulation rate and course of development. Since midline and temporal lobe components respond differently to experimental manipulations, it can be concluded that the midline and temporal lobe responses are mediated by different generator sources. The particular orientation of the generators responsible for the MLR in the guinea pig and gerbil facilitates the identification of individual components. Results from simultaneous recordings of these components during experimental manipulations support the hypothesis of multiple MLR generators in laboratory animals and provide insight into the generators and developmental aspects of the MLR in humans.

Acoustic Stimulation↗

Viewing the audiogram through a mathematical model.

In an effort to better quantify audiometric results, audiograms were modeled with a hyperbolic tangent function of the form: t = a tanh [(f-c)/b] + d, where t = threshold and f = frequency. The parameters, a, b, c, and d, were determined for a specific audiogram via a least-squares nonlinear curve fitting technique. The parameters describe salient features of the audiogram. The point (c,d) is the midpoint of the sloping portion of the audiogram, while a and b describe the slope. Other features of the configuration can be described by combinations of the parameters. This approach quantifies the entire audiogram and allows simple correlations of routinely gathered clinical data. To demonstrate the application of the model, a small data set of 500 Hz ABR and behavioral thresholds recorded from 28 ears (23 subjects) was analyzed. The model showed that agreement between the thresholds varied with audiometric configuration.

Adolescent↗

Color imaging of the human middle latency response.

Color imaging brain mapping techniques were applied to the middle latency response in 40 normal-hearing, neurologically intact adults. Stimuli included 9/sec and 41/sec clicks and 500 and 2000 Hz tone bursts. Wave Na had no specific focus of activity while wave Pa was largest in amplitude over the vertex and frontal lobes. Variables such as the baseline from which amplitude measures are made (prestimulus versus preceding wave) and reference electrode (ipsilateral mastoid versus C7) were assessed. The preceding trough (Na) yielded a more precise measure of Pa amplitude than the prestimulus baseline. The reference electrode location did not influence the topography of wave Pa, although response amplitudes were significantly larger with the noncephalic reference. Two averaging strategies were assessed: (1) averaging the entire pre- and poststimulus epoch point for point across individuals and (2) averaging the voltage of Pa at the latency of Pa for each individual. The z statistic was evaluated as a means for identifying clinically encountered abnormalities. The use of this measure was found to be problematic because such an analysis assumes normally distributed data while Pa amplitude approximates a gamma distribution. The z statistic may be more appropriate for the analysis of interhemispheric differences, which have a normal distribution with a mean close to zero. Responses obtained to 500 Hz stimuli tended to be larger than 2000 Hz-elicited responses. Of interest clinically, is that Pa amplitude was largest at electrode location Fz. The scalp topography and subsequent conclusions regarding 9 versus 41/sec responses differed depending on the data analysis strategy used, emphasizing the importance of these strategies. Future directions for this technology were discussed.

Adult↗

Toward a strategy for analyzing the auditory middle-latency response waveform.

The present paper describes for the auditory middle latency response (MLR) an analysis strategy which includes measures of latency, amplitude, waveform width, and area under the waveform. This combination of parameters can adequately describe the MLR and allow reliable and comprehensible comparisons of experimental conditions within and across studies. MLRs were recorded from normal-hearing adults utilizing a variety of recording filter settings, stimulus frequencies and stimulus envelopes. A filter window narrower than 3-300 Hz caused marked distortions in the MLR and significantly affected all parameters. Lower stimulus frequencies yielded significantly larger MLR amplitude, width, and area compared to higher frequencies. Stimulus envelope had no effect on any parameter.

Acoustic Stimulation↗

Hearing loss in an institutionalized mentally retarded population. Identification by auditory brainstem response.

We report the results of auditory brainstem response testing of 122 profoundly retarded institutionalized children, a segment of the retarded population heretofore generally regarded as untestable by behavioral audiometry. Major findings include: 32% of the study population showed, by auditory brainstem response, hearing loss exceeding 20 decibels of hearing level in one or both ears (12% showed conductive loss and 20% sensorineural loss); of the 15.6% with evidence of bilateral sensorineural loss, 7.37% had losses in the 30- to 50-dB range, and 8.19% had losses of 60 dB or greater; and evidence of abnormal brain-stem function was found in 11%. Results of otologic examinations and audiologic habilitative follow-up in selected children are also reported.

Adolescent↗