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Biomedical subjects

T McGee

Publications and source records attributed to T McGee.

51 records · Page 3Linked to original sources

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↗

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↗

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↗

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↗

The indices of potency for intravenous anaesthetics.

In rat experiments, the relative potency an safety of thiopentone, diazepam and etomidate were assessed using different indices of anaesthesia - loss of righting reflex, prevention of movement and heart rate responses to an noxious stimulus. Log-probit dose-response curves for these end-points and for lethal effect were determined. Etomidate proved to be more potent than thiopentone or diazepam; its relative potency figures varied from 5 to 18 with the use of different end-points of anaesthesia. According to the ED50 level of response for the loss of righting reflex and increased of heart rate, diazepam was more potent than thiopentone. At the same time it was less potent in the prevention of movement response. Etomidate has an extremely large standard safety margin (SSM) regarding the loss of righting reflex; with the use of movement response or heart rate response, the SSM for etomidate was close to that of thiopentone. With diazepam, SSM for movement response and heart rate response was negative (anaesthetic dose-response curve partially overlaps the lethal curve); it was positive for the loss of righting reflex. The extreme variability in assessment of relative potency and safety with different end-points of anaesthesia probably indicates that the indices used reflected various components of anaesthesia. It seems likely that for the proper assessment of the potency of intravenous anaesthetics, one index of potency is not sufficient. Several indices of potency corresponding to different components on general anaesthesia must be used.

Anesthesia, Intravenous↗

Psychophysical tuning curves and auditory thresholds after hair cell damage in the chinchilla.

Chinchillas were treated with kanamycin sulfate (150--200 mg/kg/day) to produce high-frequency hearing loss extending to about 4.0 kHz. Thresholds and psychophysical tuning curves (PTCs) were obtained before and after treatment, utilizing a shuttlebox avoidance procedure, and cochlear hair cells were evaluated under phase contrast microscopy. Hair cell loss resulting from kanamycin treatment varied from restricted lesions of the outer hair cells (OHCs) in the cochlear base, with no loss of inner hair cells (IHCs), to more extensive lesions involving both OHCs and IHCs. Threshold shift of at least 40 dB was always associated with OHC loss. PTCs obtained from frequency regions exhibiting 40--50 dB of threshold shift were normal in shape. With threshold shift in excess of 50 dB, PTCs were progressively distorted, with truncation of the tip segment and in some cases increased sensitivity of the tail segment. The results suggest that the threshold of optimally functional IHCs after kanamycin-induced OHC loss is about 40 dB higher than normal. Threshold shift in excess of 40 dB may represent IHC damage. IHCs are capable of transducing the fine-frequency information necessary for generating normally sharp PTCs in the absence of OHCs. However, with threshold shift in excess of approximately 50 dB, this frequency resolution is increasingly compromised.

Animals↗

Binaural stimulation reveals functional differences between midline and temporal components of the middle latency response in guinea pigs.

Two morphologically distinct auditory middle latency response (MLR) wave forms can be recorded from the surface of the guinea pig brain. The temporal response is recorded from the temporal lobe contralateral to the stimulus ear, and the midline response is recorded over the posterior midline. Experimental evidence suggests that different neural generators contribute to the two responses. Furthermore, it appears that the temporal response principally reflects activity of the primary auditory pathway while the midline response reflects non-primary pathways. Although it is known that neurons throughout the auditory pathway exhibit distinct binaural interaction (BI) properties, thus far there have been no systematic attempts to differentiate the MLR wave forms in response to binaural stimulation. The purpose of this study was to determine if binaural click stimulation could functionally differentiate the midline and temporal MLR responses in the guinea pig. Binaural click stimulation caused a significant decrease in temporal MLR peak amplitudes, and a significant increase in midline MLR amplitudes. The fact that different BI patterns were observed suggests that the two MLR components are functionally distinct. The data further support the hypothesis that the midline and temporal MLR in guinea pigs reflect different neural generators and pathways.

Acoustic Stimulation↗

Acoustic versus phonetic representation of speech as reflected by the mismatch negativity event-related potential.

The concept of categorical perception of speech and speech-like sounds has been central to models of speech perception for decades. Event-related potentials (ERPs) provide a neurophysiologic perspective of this important phenomenon. In the present experiment the mismatch negativity (MMN) event-related potential, which is sensitive to fine acoustic differences, was recorded in adults. Of interest was whether the MMN reflects the acoustic or categorical perception of speech. The MMN was elicited by stimulus pairs (along a continuum varying in place of articulation from /da/ to /ga/) which had been identified as the same phoneme /da/ (within category condition) and as different phonemes /da/ and /ga/ (across categories condition). The acoustic differences between these two pairs of stimuli were equivalent. The MMN was observed in all subjects both in the within and across category conditions. Furthermore, the MMN did not differ in latency, amplitude or area within and across categories. That is, the MMN indicated equal discrimination both across and within categories. These results suggest that the MMN appears to reflect the processing of acoustic aspects of the speech stimulus, but not phonetic processing into categories. The MMN appears to be an extremely sensitive electrophysiologic index of minimal acoustic differences in speech stimuli.

Acoustic Stimulation↗

Mismatch negativity in school-age children to speech stimuli that are just perceptibly different.

The mismatch negativity event-related potential (MMN) was elicited in normal school-age children in response to just perceptibly different variants of the speech phoneme /da/. A significant MMN was measured in each subject tested. Child and adult MMNs were similar with respect to peak latency and duration. Measures of MMN magnitude (peak-to-peak amplitude and area) were significantly larger in children than in adults. The results of the present study indicate that the MMN can be elicited in response to minimal acoustic stimulus differences in complex speech signals in school-age children. The results support the feasibility of using the MMN as a tool in the study of deficient auditory perception in children.

Acoustic Stimulation↗