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Biomedical subjects

G Kidd

Publications and source records attributed to G Kidd.

At least 19 recordsLinked to original sources

Axonal loss in normal-appearing white matter in a patient with acute MS.

BACKGROUND: Brain imaging studies detect abnormalities in normal-appearing white matter in patients with MS. OBJECTIVE: To investigate the histopathologic basis for these changes in autopsy tissue from a patient with MS with 9 months' disease duration and a terminal brain stem lesion. METHODS: The brain stem and spinal cord were analyzed ultrastructurally and immunocytochemically for axons, myelin, and activated microglia/macrophages. RESULTS: Pathologic findings were consistent with a terminal inflammatory demyelinated lesion at the cervicomedullary junction. The ventral spinal cord column, containing descending tracts, exhibited 22% axonal loss at segment C7, but grossly normal immunostaining for myelin. Confocal and electron microscopy revealed myelin sheaths without axonal content and initial stages of myelin degradation by activated microglia/macrophages among intact myelinated axons. Axonal number and appearance was normal in ascending sensory tracts. CONCLUSIONS: These studies confirm axonal degeneration in the absence of myelin loss as one histopathologic correlate to abnormal MR findings in patients with MS.

Acute Disease↗

Cell death and immunohistochemistry of p53, c-Fos and c-Jun after spermine injection into the rat striatum.

Administration of polyamines into the central nervous system results in tissue damage, possibly through the excitotoxic actions of the NMDA receptor. Direct injection of 100 nmol of spermine into the rat striatum produced a lesion equivalent to approximately 50% of the striatum. Analysis of the DNA in this region revealed the distinct ladder-like pattern of degradation often associated with apoptosis. This DNA fragmentation was confirmed in vivo using terminal deoxynucleotidyl-transferase-mediated biotinylated deoxyuridine triphosphate nick end labelling (TUNEL). The morphology of the TUNEL-positive cells showed marked differences at the needle tract when compared with cells in damaged areas away from the needle tract, suggesting a differential mechanism of cell death in these two regions. The patterns of p53, c-Fos and c-Jun protein expression were determined using immunohistochemistry. The number of p53-immunoreactive cells increased up to 14 h and returned to basal levels by 24 h. c-Fos protein expression transiently increased, peaking at 8 h after injection. c-Jun exhibited a protracted pattern of expression, remaining elevated up to 24 h. p53 protein expression was colocalised with TUNEL staining in areas away from the needle tract, but not in cells at the needle tract, suggesting once again a differential mechanism of cell death. At 14 h, c-Fos and c-Jun were not colocalised with TUNEL staining, suggesting that they are either not involved with the cell death process or that the time course of protein expression and the onset of DNA fragmentation do not overlap. This work represents the first characterisation of processes associated with cell death induced by spermine in vivo.

Animals↗

Evidence for spatial tuning in informational masking using the probe-signal method.

Auditory spatial attention is one mechanism that may contribute to the ability to identify one sound source in a multi-source environment. The role of auditory spatial attention in a multi-source environment was investigated using the probe-signal method. The experiment took place in a quiet room with seven speakers arranged in a semi-circle in front of the listener. The speakers were placed at 30-degree intervals at a distance of 5 ft from the listener. The signal was comprised of eight contiguous, 60-ms pure-tone bursts arranged in either a rising or falling frequency pattern. Masker components were also comprised of eight contiguous pure-tone bursts but with durations that varied randomly from 20 to 100 ms. The six maskers were played with the signal and were constructed in order to result in informational rather than energetic masking. The frequency of each masker component was chosen randomly on each burst from a narrow frequency band, independent from the signal frequency band. The task was 1I-2AFC fixed-level identification with response time measurement. The listener was instructed to focus attention on a specified speaker (expected location) for a block of trials. Accuracy and response time were compared across two conditions: (1) signal presented at the expected location and (2) signal presented at an unexpected location. Results indicate a significant increase in accuracy and faster response time when the signal was presented at the expected location as compared to an unexpected location. These results suggest that auditory spatial attention plays an important role in multi-source listening, especially when the listening environment is complex and uncertain.

Adult↗

Neurological disability correlates with spinal cord axonal loss and reduced N-acetyl aspartate in chronic multiple sclerosis patients.

Axonal degeneration has been proposed as a cause of irreversible neurological disability in multiple sclerosis (MS) patients. The purpose of this study was to quantify axonal loss in spinal cord lesions from 5 paralyzed (Expanded Disability Status Scale score > or =7.5) MS patients and to determine if axonal number or volume correlated with levels of the neuronal marker N-acetyl aspartate (NAA). Axonal loss in MS lesions ranged from 45 to 84% and averaged 68%. NAA levels were significantly reduced (>50%) in cross sections of spinal cords containing MS lesions. Reduced NAA correlated with reduced axonal numbers within lesion areas. In addition, NAA levels per axonal volume were significantly reduced in demyelinated axons (42%) and in myelinated axons in normal-appearing white matter (30%). The data support axonal loss as a major cause of irreversible neurological disability in paralyzed MS patients and indicate that reduced NAA as measured by magnetic resonance spectroscopy can reflect axonal loss and reduced NAA levels in demyelinated and myelinated axons.

Adult↗

Release from masking due to spatial separation of sources in the identification of nonspeech auditory patterns.

A nonspeech pattern identification task was used to study the role of spatial separation of sources on auditory masking in multisource listening environments. The six frequency patterns forming the signal set were comprised of sequences of eight 60-ms tone bursts. Bursts of masking sounds were played synchronously with the signals. The main variables in the study were (1) the difference in spatial separation in the horizontal plane between signals and maskers and (2) the nature of the masking produced by the maskers. Spatial separation of signal and masker ranged from 0-180 degrees. The maskers were of two types: (1) a sequence of eight 60-ms bursts of Gaussian noise intended to produce predominantly peripherally based "energetic masking" and (2) a sequence of eight 60-ms bursts of eight-tone complexes intended to produce primarily centrally based "informational masking." The results indicated that identification performance improved with increasing separation of signal and masker. The amount of improvement depended upon the type of masker and the center frequency of the signal patterns. Much larger improvements were found for spatial separation of the signal and informational masker than for the signal and energetic masker. This was particularly apparent when the acoustical advantage of the signal-to-noise ratio in the more favorable of the two ears (the ear nearest the signal) was taken into account. The results were interpreted as evidence for an important role of binaural hearing in reducing sound source or message uncertainty and may contribute toward solving the "cocktail party problem."

Adult↗

Axons regulate the distribution of Schwann cell microtubules.

It is well established that axons regulate Schwann cell phenotype. The purpose of the present study was to determine whether axons influence the arrangement of Schwann cell microtubules (MTs). Using double-labeling immunocytochemistry and confocal microscopy, we show that MTs in undifferentiated Schwann cells are nucleated from and attached to a single MT organizing center (MTOC) that is associated with the centrosome. Physical contact with appropriate axons initiates a myelin-forming phenotype that disperses MT minus ends and induces multiple MT-nucleating sites in Schwann cell perinuclear cytoplasm. The axonal signal that initiates myelin breakdown during Wallerian degeneration induces multiple MTOCs and MT bundles in Schwann cell perinuclear cytoplasm and in cytoplasm between degenerating myelin ovoids. These results establish that axons influence Schwann cell MT distribution by regulating the location and number of MT-nucleation sites.

Animals↗

Phase independence of pitch produced by narrow-band sounds.

Three listeners matched the pitch of a simple tone to that of narrow-band complex signals having different phases. The pitch matches were independent of the phases; the frequency of the simple tone approximately equaled the center of gravity of the power spectrum of each complex signal. This result is inconsistent with a model that calculates the pitch of a waveform as the average of instantaneous frequency weighted by the envelope of the waveform.

Humans↗

Discriminating coherence in spectro-temporal patterns.

This study examined the ability of trained listeners to discriminate coherent components in randomly varying spectral patterns. In each observation interval, the listener was presented with a sequence of bursts of multitone complexes having a fixed number of tones (m) in each burst. In the standard interval, the frequency of each tone in every burst was chosen randomly between 200 and 5000 Hz. In the signal interval, the frequencies of n tones were repeated throughout the burst sequence while the remaining m-n tones were chosen at random. The n tones were coherent in the sense that they were perceived as "sticking together" to form a pattern. The listener's task was to discriminate which burst sequence contained the n components. The results indicated that discrimination improved with increasing n/m, with increasing number of bursts per interval, and declined as the coherent components were increasingly perturbed in frequency. Further, for a fixed value of the ratio n/m discriminability was relatively independent of m. A model incorporating multichannel filtering and an optimum decision rule was reasonably successful in accounting for the experimental results.

Adult↗

Binaural advantage for sound pattern identification.

Listeners were trained to identify six patterns of eight sequentially presented 48-ms tone bursts. The variation in frequency forming the patterns was confined to a relatively narrow range around the nominal center frequency, which was either 500, 1000, or 3000 Hz, or was selected randomly on each presentation from a range of 450-3300 Hz. Detection (500 and 3000 Hz only) and identification of the six patterns masked by Gaussian noise was measured in two interaural presentation conditions: masker in-phase and signal in-phase (NoSo), and masker in-phase and signal pi rad out-of-phase (NoS pi). The differences in performance in the two interaural presentation conditions for detection and identification are referred to as "masking-level differences" (MLDs) and "identification-level differences" (IDLDs), respectively. At 500 Hz, MLDs and IDLDs were about 11-13 dB. At 3000 Hz, the MLDs and IDLDs were about 1-3 dB. For the random-center-frequency condition, the slopes of the identification-level functions were much shallower for the NoS pi condition than for the NoSo condition so the binaural advantage was large at low signal-to-noise ratios and declined as signal-to-noise ratio increased. This finding was due to the broad frequency range over which the information was distributed and the decline in the binaural advantage with increasing frequency, a conclusion consistent with that reported for the binaural advantage for speech intelligibility. A second experiment demonstrated that MLDs and IDLDs could be manipulated independently: A 500-Hz tone was added to each element of the 3000-Hz patterns. A large MLD was found--due to detection of the 500-Hz tone--while the identification-level functions were determined solely by the high-frequency information, which produced small IDLDs. Finally, the Gaussian noise masker was replaced by an informational masker comprised of eight randomly chosen eight-tone bursts played simultaneously with the signal-pattern elements which were centered at 1000 Hz. Large amounts of informational masking were found for identification. The slopes of the identification-level functions were much shallower than found for the Gaussian noise masker and a relatively small binaural advantage (about 5 dB) was observed.

Adult↗

Improving the detectability of a brief tone in noise using forward and backward masker fringes: monotic and dichotic presentations.

A brief tonal signal simultaneously masked by a brief noise burst became easier to hear when the masker duration was increased. The signal was a 1000-Hz tone, 4 ms in duration; the masker was a wideband noise having a spectral notch 1400 Hz wide centered at 1000 Hz. Compared to performance with a 22-ms burst masker, average detection threshold across five subjects improved by 15 dB when a 150-ms masker "fringe" preceded the signal (forward fringe), and by 9 dB when the masker fringe followed the signal (backward fringe). Little improvement was observed in either condition when the fringe was presented to the ear contralateral to the signal/burst complex. However, when the fringe was presented to both ears and the signal/burst complex to just one ear, the forward fringe was about as helpful as when the stimuli were presented monotically, but the benefit of the backward fringe was substantially reduced. The backward-fringe advantage was restored by reducing the level, or delaying the onset, of the contralateral component of the fringe. The results suggest that the forward-fringe advantage is a robust phenomenon that is largely insensitive to input to the contralateral ear. In contrast, the backward-fringe advantage appears to be a fragile effect that can be affected by inputs from both ears.

Acoustic Stimulation↗

Reducing informational masking by sound segregation.

Informational masking was reduced using three stimulus presentation schemes that were intended to perceptually segregate the signal from the masker. The maskers were sets of sinusoids chosen randomly in frequency and intensity on each stimulus interval or, in some conditions, on every masker burst in a series of bursts within intervals. Masker components were excluded from the frequency region surrounding the 1000-Hz signal to minimize the energetic masking. Masked thresholds as great as 60-70 dB above quiet threshold were observed for some subjects in some conditions. It was shown that this informational masking could be reduced as much as 40 dB by: (1) presenting the masker to both ears and signal to one ear; (2) playing different masker samples sequentially in each interval of every trial; or (3) presenting the signal in alternate bursts of multiple, identical masker samples. For the binaural manipulation, informational masking was reduced because the masker and signal were perceived as originating from different interaural locations. In the latter two manipulations, a difference in the spectral or temporal pattern of the signal and masker provided the detection cue. These effects were interpreted as evidence of the importance of perceptual segregation of sounds in noisy listening environments where signal reception is not limited by energetic masking.

Acoustic Stimulation↗

Auditory detection of the human brainstem auditory evoked response.

The human brainstem auditory evoked response (BAER) is a far-field electrical potential recorded from the scalp in response to transient acoustic stimuli. Typically, voltage measurements are obtained for a period of about 10 msec following the acoustic stimulus, which is repeated and summed several hundred or thousand times to permit extraction of the response from ongoing nonauditory neural activity. The judgment about whether a response has been obtained is normally based on the pattern observed in a visual display of the waveform. In this study, we investigated whether listeners can distinguish BAERs elicited by acoustic clicks from control waveforms obtained with no acoustic stimulus when the waveforms were presented auditorily. For this purpose, BAER and control waveforms were transduced by an earphone and used in an auditory detection task. Several presentation strategies were examined, including lengthening the waveform by playing it at a lower sampling rate, playing the waveform repetitively, and using the waveform to frequency modulate a pure-tone carrier. The results indicated that the BAER, when extended in duration and used to frequency modulate a 1000-Hz pure tone, was highly detectable in a YES-NO paradigm for BAERs elicited with high-level (e.g., 70 dB re. behavioral detection threshold) acoustic clicks. Performance declined to near chance as the level of the BAER-eliciting stimulus was lowered to 10 dB. In general, detection performance for stimuli presented visually was slightly, but consistently, superior to that which occurred for stimuli presented auditorily.

Acoustic Stimulation↗

Individual differences in the improvement in spectral shape discrimination due to increasing number of nonsignal tones.

The effect of the number of nonsignal tones on the just-discriminable difference in spectral shape was evaluated for 12 naive subjects. The signal was an intensity increment to the center tone of a multitone complex. The tones were spaced at equal frequency ratios and, except for the signal increment, were equal in level. The number of nonsignal tones ranged from 2 to 20. Consistent with previous studies using equally spaced components, group mean thresholds improved monotonically with increasing number of tones. Group mean thresholds improved about 8 dB over the range of reference spectra employed. Large differences were found across subjects in overall performance, and in the magnitude of the improvement with increasing number of nonsignal tones. The greatest intersubject variability was observed for the stimuli composed of the fewest components. It was concluded that the differences reported in the literature concerning the presence and magnitude of the improvement are due both to differences in the procedures used and to the large individual differences that occur among subjects.

Acoustic Stimulation↗

Discriminability of narrow-band sounds in the absence of level cues.

Several experiments are described in which the task of the observer was to detect an intensity increment to the center tone of a narrow-band, multitone complex. The sound-pressure levels of the stimuli were equated, then randomized, so that listeners could not detect the signal by using level cues. The primary experimental variables were the number of tones in the masker spectrum, the level of the center tone or "pedestal" relative to the other tones, the center frequency and the sound-pressure level. Both "random-phase" and "fixed-phase" conditions (referring to whether the pattern of starting phases of the nonsignal tones was chosen randomly on every presentation or was held constant throughout each trial and block of trials) were tested. Although no simple detection strategy appeared to account for all of the results, the most plausible explanation for performance in most conditions was that the listeners were able to discriminate between sounds based on subtle differences in the amplitude envelopes of the waveforms.

Adult↗

A composite randomization procedure for measuring spectral shape discrimination.

In studies of auditory profile analysis [D. M. Green, Profile Analysis: Auditory Intensity Discrimination (Oxford U. P., New York, 1988)], the sounds are presented at random levels to discourage the listener from basing the discrimination on a difference in absolute level rather than on a difference in the shape of the spectrum. A difference in absolute level, however, can still provide an effective discrimination cue if the difference is comparable to the range of randomization. Using enormous ranges of random levels is not desirable, because it is distracting to normal listeners and may exceed the dynamic range of hearing for listeners with hearing loss. This article describes a new experimental procedure which permits the experimenter to greatly reduce the range of level randomization in roving-level tasks.

Acoustic Stimulation↗

A new technique for measuring spectral shape discrimination.

A new technique is described for studying the ability of listeners to discriminate between sounds on the basis of spectral shape, a process called "auditory profile analysis." The advantage of the technique is that it reduces the range of the random rove in level necessary to provide a specified limit on the performance which listeners could achieve by "level detection;" that is, by employing a detection strategy based solely on comparisons of stimulus level. Thresholds were measured for the just-discriminable "ripple" (a pattern of alternating intensity increments and decrements) in an equal-amplitude, multitone reference spectrum for a group of normal-hearing listeners. Broadband, high-pass and low-pass filtered conditions were tested. The results indicated that the thresholds obtained using the new technique were well below the lowest level achievable by level detection (referred to as the "level-detection limit") in all conditions using a 20-dB random within-trial rove in overall level. The lowest threshold occurred for the broadband stimulus while the highest threshold was observed for the most extreme high-pass filtered condition. The new technique appears to be well-suited for study of profile analysis in hearing-impaired listeners where stimulus bandwidth and rove range are limited.

Acoustic Stimulation↗

Evaluation of simple models of auditory profile analysis using random reference spectra.

This article describes further study of the finding reported by Green et al. [J. Acoust. Soc. Am. 73, 639-643 (1983)] and others that, in certain conditions, the threshold of detectability for an intensity increment to the center tone of a multitone reference spectrum decreased as the number of nonsignal tones increased. That result was considered remarkable since critical-band theory would predict that these nonsignal tones, spaced outside the "critical band" containing the signal, would have no effect on or, at most, slightly decrease within-band detectability--and certainly could not account for the result of improved detectability found in the study cited above. Recently, Henn and Turner [J. Acoust. Soc. Am. 88, 126-131 (1990)] were unable to replicate the result described above, concluding that the phenomenon exists only in "limited conditions" and that is "highly individual" in nature. Further, they speculated that the most likely reason for the discrepancy between their study and previous studies was the selection and/or training of the observers. The present study addressed the effects of the amount of subject training on the finding of Green et al. while controlling the potential effects of stimulus order. Specifically, for a group of three "naive" listeners, thresholds were measured for 3-, 7-, and 21-tone inharmonic complexes as a function of the amount of practice in a mixed-block design. In all cases the group mean thresholds decreased as the number of nonsignal tones increased both initially and after extensive practice for both fixed- and roving-level conditions. Thus the effect does not appear to be an artifact of the amount or order of training subjects receive. The possible role of subject sample size and the magnitude of individual differences in obtaining the effect remains an open question. Two hypotheses suggested to account for the improvement in threshold with increasing number of nonsignal tones were evaluated. The hypotheses were represented by simple mathematical models, referred to as the "multiple-comparison" and "pitch-cue" models. The predictions of both models were compared with the results of a series of detection experiments in which the independent variables were the number of nonsignal tones and amount of random, within-trial "amplitude perturbation" [cf. Kidd et al., J. Acoust. Soc. Am. 79, 1045-1053 (1986)] of the nonsignal tones. Neither model, as applied, provided a satisfactory account of the effects of the main variables of number of tones and amount of perturbation.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗