Biomedical subjects

T McGee

Publications and source records attributed to T McGee.

At least 19 recordsLinked to original sources

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1991

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↗

PubMed1990

The hearing-impaired infant: patterns of identification and habilitation revisited.

This study is a follow-up of an 1980-1982 study that examined the occurrence of risk factors and the patterns of identification and habilitation in a group of hearing-impaired infants from an urban setting. Current findings covering the period 1983-1988, indicate that only one out of three hearing-impaired infants can be expected to be identified through audiological screening programs in Neonatal Intense Care Units (NICUs) and although the age at diagnosis for NICU graduates is significantly earlier than for Well Baby Nursery (WBN) graduates, age at enrollment in a parent-infant program for both NICU and WBN infants is around 20 months. Over the 8 year period covered by our two studies, the age hearing-impaired infants are enrolled in habilitation has remained a year or more later than the 6 month ideal recommended in 1982 by the Joint Committee on Infant Hearing.

Chicago↗

PubMed1990

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↗

PubMed1989

Structure and expression of the murine retinoblastoma gene and characterization of its encoded protein.

We have isolated a cDNA clone of the murine homologue of the human retinoblastoma (Rb) susceptibility gene. DNA sequence analysis reveals a high degree of conservation with the human Rb sequence, both in the coding and in the noncoding regions. The predicted amino acid sequence of the mouse Rb protein shows 91% identity to that of the human protein. Both proteins were found to contain a peptide sequence reminiscent of a leucine-repeat motif ("leucine-zipper") that is also found in the myc, fos, and jun oncogenes. Synthetic peptide antiserum directed against a portion of the mouse Rb protein detects three proteins of 104-110 kDa in cells that were transiently transfected with a mouse Rb gene expression construct. In the mouse embryo the expression of Rb mRNA was ubiquitous, with maximal expression being observed around 13 days of gestation. In the embryo, the highest level of expression was observed in liver and brain. In contrast, the Rb gene was found to be expressed at a very low level in adult mouse liver with high levels being found in lung, thymus, and spleen. A shorter Rb transcript was detected in mouse testes.

Amino Acid Sequence↗

PubMed1989

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↗

PubMed1989

Speech recognition measures with noise suppression hearing aids using a single-subject experimental design.

Research aimed at quantifying the benefits a hearing aid user might expect from noise suppression hearing aids purported to improve hearing in the presence of background noise have yielded widely varying results. We suggest this may in part be due to the inappropriate use of experimental approaches based on group design and inferential statistical analysis. Included in this paper is our rationale for employing a single-subject experimental design to investigate subject performance with two commercially available hearing-aid noise suppression systems. Preliminary results with two subjects indicate that both the Siemens Automatic Signal Processing (ASP) and Zeta Noise Blocker (ZNB) noise suppression systems markedly improve listener scores on the low predictability sentence material of the SPIN Test. We conclude these two noise suppression systems may improve performance as the listening situation becomes contextually more difficult, and that single-subject experimental designs could be a valuable addition to applied behavioral research with hearing aids.

Evaluation Studies as Topic↗

PubMed1988

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↗

PubMed1988

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↗

PubMed1988

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↗

PubMed1988

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↗

PubMed1988

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↗

PubMed1987

Development of the middle latency response in an animal model and its relation to the human response.

Although the clinical use of the middle latency response (MLR) in adults is fairly straightforward, its use is complicated by maturational changes that continue throughout the first decade of life. In order to telescope the time period of this long developmental course, we have approached the study of MLR maturation using the gerbil as an animal model. The course of MLR obtained over the temporal lobe development was characterized in the Mongolian gerbil ranging in age from 10 days to 3 months of life. The adult gerbil MLR consists of two positive peaks (A and C) at 11 and 25 ms, respectively, and a negative component (B) at 16 ms. These components emerge in a systematic fashion as a function of age. The present work supports a strong age effect of increased MLR detectability in the gerbil, similar to findings reported for humans. Wave A was infrequently detected in young animals, but when present, it occurred at adult latencies. The latency of waves B and C decreased systematically with age. The amplitude of all components increased with age, similar to findings in humans. The fact that adult-like thresholds were obtained shortly after birth indicates that when present, MLRs may be a good index of hearing threshold. Effects of stimulating across a wide range of intensities were described. The gerbil model appears appropriate for the study of development of the central auditory system function.

Age Factors↗

PubMed1987

Rate and filter effects on the developing middle-latency response.

Auditory middle-latency responses (MLRs) were obtained from 71 unanesthetized gerbils ranging in age from 10 to greater than 90 days. Effects of age, stimulation rate, high- and lowpass filter settings and filter slope were examined. MLR amplitude decreased significantly with increased stimulation rate at all ages, at rates up to 40/s. The detection of MLR waves (presence or absence) varied inversely with the rate of stimulation only in immature subjects. The amplitude of waves B (15 ms) and C (25 ms) was significantly larger with a highpass filter setting of 3 Hz as compared to 10 and 30 Hz. This effect was significantly more pronounced in developing animals as compared to adults. MLR amplitude was greater with a filter slope of 6 dB/octave as compared to 48 dB/octave, (10-2,000 Hz) and this effect was also significantly greater in developing animals than in adults. There was no interaction between lowpass filter setting and age (100 vs. 2,000 Hz). A prominent positive wave occurring at approximately 50 ms was present in the 48 dB/octave condition although it was not observed with 6 dB/octave filtering. The clinical use of the MLR requires a better understanding of the effects of stimulus and recording procedures on the response, and how they vary as a function of subject age.

Aging↗

PubMed1987

Cholinergic receptor mutants of the nematode Caenorhabditis elegans.

Potential acetylcholine receptor (AChR) mutants of the nematode are selectable by resistance to the neurotoxic drug levamisole, a probable cholinergic agonist. To determine which mutants may have achieved resistance through loss of levamisole receptor function, we have assayed mutant extracts for specific 3H-meta-aminolevamisole binding activity in the presence and absence of mecamylamine. We find that mutants in 3 of the 7 genes associated with extreme levamisole resistance are obviously deficient in saturable specific 3H-meta-aminolevamisole binding activity. Mutants of the 4 other genes have abnormal binding activities that fail to undergo the apparent allosteric activation of saturable specific 3H-meta-aminolevamisole binding activity caused by mecamylamine. Thus, all 7 genes appear to be required to produce a fully functional levamisole receptor. Mutants of several other genes associated only with partial resistance to levamisole have at least grossly normal receptor binding activities.

Animals↗