Biomedical subjects

T McGee

Publications and source records attributed to T McGee.

At least 37 records · Page 2Linked to original sources

PubMed1994

Discrimination of speech-like contrasts in the auditory thalamus and cortex.

The neurophysiologic discrimination of acoustic contrasts was investigated as reflected by the mismatch negativity (MMN) response. Evoked responses were recorded from guinea pig thalamus (medial geniculate nucleus) and epidural surface in response to synthesized speech contrasts /ga/-/da/ and /ba/-/wa/. From the caudomedial portion of the medial geniculate nucleus, /ba/-/wa/ elicited a strong mismatch response, whereas /ga/-/da/ did not. Neither stimulus contrast elicited an MMN from the ventral, or primary, portion of medial geniculate. Both stimulus contrasts elicited an MMN from the midline surface. Neither contrast elicited an MMN from the surface over the temporal lobe. Results indicate a hierarchy of processing of the spectrotemporal changes which characterize formant transitions. Also, results indicate that the nonprimary portions of the auditory pathway contribute substantially to the MMN.

Animals↗

PubMed1994

Nonprimary auditory thalamic representation of acoustic change.

1. The mismatch response, or mismatch negativity (MMN), is a neurophysiologic response to stimulus change. In humans and other animals, the MMN may underlie the ability to discriminate acoustic differences, a fundamental aspect of auditory perception. 2. This study investigated the role of the thalamus in the generation of a tone-evoked MMN in guinea pigs. Electrodes were placed in the caudomedial (nonprimary) and ventral (primary) subdivisions of the auditory thalamus (medial geniculate nucleus). Surface epidural electrodes were placed at the midline and over the temporal lobe. The MMN was elicited by a deviant stimulus (2,450-Hz tone burst) embedded in a sequence of standard stimuli (2,300-Hz tone bursts). 3. A tone-evoked MMN was present in nonprimary thalamus but was absent in the primary thalamus. Surface-recorded MMNs were measured at the midline but not over the temporal lobe. The correspondence between nonprimary thalamic responses and midline surface potentials, and between primary thalamic responses and temporal surface potentials, is consistent with data reported for the auditory middle latency responses in guinea pigs. 4. The results demonstrate that the nonprimary auditory thalamus contributes to the generation of a tone-evoked MMN in the guinea pig. Furthermore, the data indicate that the guinea pig is a feasible model for investigating central auditory processes underlying acoustic discrimination.

Acoustic Stimulation↗

PubMed1993

The mismatch negativity cortical evoked potential elicited by speech in cochlear-implant users.

The mismatch negativity (MMN) event-related potential is a non-task related neurophysiologic index of auditory discrimination. The MMN was elicited in eight cochlear implant recipients by the synthesized speech stimulus pair /da/ and /ta/. The response was remarkably similar to the MMN measured in normal-hearing individuals to the same stimuli. The results suggest that the central auditory system can process certain aspects of speech consistently, independent of whether the stimuli are processed through a normal cochlea or mediated by a cochlear prosthesis. The MMN shows promise as a measure for the objective evaluation of cochlear-implant function, and for the study of central neurophysiological processes underlying speech perception.

Acoustic Stimulation↗

PubMed1993

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↗

PubMed1993

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↗

PubMed1993

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↗

PubMed1993

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↗

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↗

PubMed1991

Phospholipid transfer proteins: a biological debut.

Eukaryotic cells contain a battery of cytosolic proteins that catalyse phospholipid movement in vitro. Current studies are now revealing some surprising aspects of the in vivo function of such proteins, and are also uncovering previously unsuspected relationships between secretory pathway function, intracellular phospholipid transport, phospholipid biosynthesis, and the dynamics of the actin cytoskeleton.

Journal Article↗

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↗