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Biomedical subjects

J H Mills

Publications and source records attributed to J H Mills.

At least 19 recordsLinked to original sources

Low-frequency component of the gerbil brainstem response: response characteristics and anesthesia effects.

The auditory brainstem response (ABR) was recorded with epidural electrodes in awake and anesthetized gerbils. Low- and high-frequency components of the ABR were separated by analog filters and compared as functions of stimulus intensity, frequency, repetition rate, and effects of anesthesia. In response to 0.5 kHz tone bursts, thresholds of the low-frequency component (LF-ABR) were significantly lower than that of the most prominent peak of the high-frequency components (wave P4). At both 2 and 4 kHz, thresholds of the LF-ABR and wave P4 were not significantly different. Changes in stimulus intensity over a 70 dB range produced similar changes in peak amplitudes and latencies for the LF-ABR and P4. However, while the amplitude of the LF-ABR was inversely related to stimulus frequency, the amplitude of P4 was reduced at 0.5 kHz, as compared to 2 and 4 kHz. Increases in stimulus rate from 7 to 100 bursts/s produced little change in the amplitude of the LF-ABR. At rates of 80 and 100 bursts/s, the LF-ABR was sinusoidal in appearance due to the proximity of successively generated potentials. In contrast, the amplitude of P4 varied inversely with stimulus rate between 20 and 100 bursts/s. Administration of ketamine and xylazine produced minor changes in the amplitudes and latencies of both the LF-ABR and wave P4. The response characteristics of the gerbil LF-ABR are similar to those of the low-frequency component of the ABR in humans and cats. The LF-ABR provides an estimate of hearing threshold at low frequencies (0.5 kHz) as well as higher frequencies (2-4 kHz). A major advantage to the LF-ABR is that it can be recorded at high stimulation rates in awake and anesthetized animals, thus providing an efficient measure of auditory function.

Acoustic Stimulation

Audiometric and subjective assessment of hearing handicap.

This study compares self-perceived assessment of hearing handicap with audiometrically derived measures of hearing handicap in a sample of elderly persons. Subjects were evaluated by traditional audiometric tests, the Speech Perception in Noise test, and the Hearing Handicap Inventory for the Elderly, a self-assessment questionnaire. Hearing handicap was also calculated by the audiometrically derived American Academy of Otolaryngology (1979) method. Our results are consistent with other studies that indicate a low correspondence between audiometric measures of hearing handicap and self-assessment of hearing handicap. Furthermore, if the Hearing Handicap Inventory for the Elderly is considered the true measure of hearing handicap, our data indicate that the American Academy of Otolaryngology method tends to overestimate handicap among persons with no self-perceived hearing handicap and underestimates handicap among persons with significant self-perceived hearing handicap.

Aged

Age-related changes in auditory potentials of Mongolian gerbil.

The Mongolian gerbil is being evaluated as an animal model of age-related hearing loss (presbyacusis). Part of this evaluation involves estimating auditory thresholds from evoked potentials arising from the auditory nerve and brainstem. The gerbils are born and reared in an environment where the ambient noise level is less than 40 dBA. Some animals are followed longitudinally (8, 19, 23.5 and 36 months), others are studied at 6-8 months (controls), or at 36 months (cross-sectional). Physiological responses are obtained with the animals anesthetized with ketamine and xylazine and transdermal electrodes attached to the head. Auditory signals are tone pips with center frequencies from 1 to 16 kHz in octave steps. Signal levels are varied from 10 to 80 dB SPL in 10 dB steps. For animals (N = 48) in the age range of 6-8 months, mean auditory thresholds were about 20 dB SPL between 2.0 and 8.0 kHz, 25 dB at 16 kHz and 30 dB at 1.0 kHz. By age 22-24 months (N = 15) thresholds had increased by about 10 dB at nearly all frequencies. By age 36 months (N = 37 ears, 32 animals) threshold increases were about 30-35 dB at 8 and 16 kHz, were 25 dB at 4 kHz and 2 kHz, and were 19 dB at 1 kHz. These hearing losses in 36-month gerbil are qualitatively similar to human data for 60-65-year-old males and 70-year-old females. Individual differences in hearing loss were large with the range exceeding 65 dB. While some animals (26/37) had a high-frequency sloping loss, others (11/37) had a bimodal audiometric shape where the hearing loss was smallest at 4 kHz and increased by at least 10 dB at adjacent frequencies.

Aged

Tuning and suppression in auditory nerve fibers of aged gerbils raised in quiet or noise.

Mongolian gerbils were reared either in quiet or in a continuous noise field (85 dBA, 500-4000 Hz). The gerbils began the noise exposure at 8 months of age and, after the exposure, spent the remainder of their lives in the quiet vivarium with the quiet-aged group. The duration of the noise exposure was between 365 and 724 days. At the terminal experiment the ages of the animals varied between 24 and 43 months, with a mean age of about 36 months, an age representing the average life span of a gerbil in our colony. During the terminal experiment, tuning curves and boundaries of two-tone rate suppression were obtained from single fibers in the auditory nerve. Threshold shifts occurred in both groups of animals. The shift was largely confined to the tip of the tuning curve; i.e., the region around the characteristic frequency (CF) of the fiber. The CF shifts effectively reduced the tip-to-tail ratios of the tuning curves. Two-tone suppression areas above and below CF were present for all fibers in the quiet-aged animals, but were often absent for fibers in the noise-aged group. The presence of suppression was largely independent of fiber thresholds in both groups of animals. Indeed, fibers were found with clearly-defined suppression boundaries above and below CF despite threshold shifts of up to 60 dB. Moreover, in the noise-aged group suppression below CF was sometimes found without concomitant suppression above CF and vice versa, suggesting an independence between the two suppression areas. For fibers with CFs within the bandwidth of the noise, two-tone suppression above CF was always absent, even though suppression below CF was sometimes present. In sum, two-tone suppression was near normal in ears aged in quiet despite relatively large threshold shifts at the fiber CF. However, suppression, especially that above CF, was vulnerable to the effects of chronic noise. Taken with the results of other studies, our data suggest that the micromechanics of the cochlea are largely responsible for two-tone suppression, especially that above CF, and that different mechanisms may underlie suppression above and below CF.

Aging

Frequency selectivity of the middle latency response.

A forward masking paradigm was used to assess the frequency selectivity of the middle latency response (MLR). Tuning curves of the MLR were obtained in unanesthetized gerbils. Changes in the amplitudes of MLR waves A, B, and C with latency values of 10 to 13 ms, 14 to 17 ms, and 20 to 25 ms, respectively, were analyzed as a function of masker frequency and intensity. Tuning curves of the MLR were also compared to tuning curves of the auditory brainstem response (ABR), which was recorded simultaneously with the MLR. The MLR and ABR differed in their response to forward masking. The MLR was reduced in amplitude or eliminated by masker stimuli that had minimal or no effect on the ABR. Forward masking often caused variable and non-monotonic changes in the amplitude of the MLR. Tuning curves of the MLR indicate that the MLR is less frequency selective than the ABR. The MLR is an electrophysiological measure of auditory function central to the auditory brainstem. Therefore, it may provide information concerning central components of normal and pathological auditory function. However, because of the variability of MLR amplitudes with forward masking, tuning curves of the MLR are difficult to obtain and are not efficient for routine measurements of frequency selectivity.

Acoustic Stimulation

Upward spread of masking, hearing loss, and speech recognition in young and elderly listeners.

Upward spreading of masking, measured in terms of absolute masked threshold, is greater in hearing-impaired listeners than in listeners with normal hearing. The purpose of this study was to make further observations on upward-masked thresholds and speech recognition in noise in elderly listeners. Two age groups were used: One group consisted of listeners who were more than 60 years old, and the second group consisted of listeners who were less than 36 years old. Both groups had listeners with normal hearing as well as listeners with mild to moderate sensorineural loss. The masking paradigm consisted of a continuous low-pass-filtered (1000-Hz) noise, which was mixed with the output of a self-tracking, sweep-frequency Bekesy audiometer. Thresholds were measured in quiet and with maskers at 70 and 90 dB SPL. The upward-masked thresholds were similar for young and elderly hearing-impaired listeners. A few elderly listeners had lower upward-masked thresholds compared with the young control group; however, their on-frequency masked thresholds were nearly identical to the control group. A significant correlation was found between upward-masked thresholds and the Speech Perception in Noise (SPIN) test in elderly listeners.

Adolescent

Anesthesia effects: auditory brain-stem response.

Auditory brain-stem responses (ABRs) were measured in the awake state and with ketamine and xylazine anesthesia in adult gerbils. Surface recorded vertex-positive components of the ABR were analyzed with respect to the awake and anesthetized states as a function of stimulus frequency. ABR thresholds were not altered with ketamine/xylazine. Small increases in peak latency were associated with anesthesia for all components except wave P1. Increases in absolute latency were progressively greater for successive peaks, reaching an average shift of 0.41 msec for wave P6. Amplitude changes with anesthesia were more variable, with increases generally seen for waves P4 and P6. Significant anesthesia effects on peak latency and amplitude were independent of stimulus frequency. These data confirm previously reported ABR sensitivity to non-barbiturate anesthesia. Direct comparisons of ABR interpeak intervals or amplitude ratios from awake versus anesthetized animals must account for the effects of barbiturate and non-barbiturate agents. However, the stability of response threshold and the small magnitude of latency and amplitude changes with a ketamine and xylazine regimen demonstrate that accurate electrophysiological measures of hearing sensitivity and auditory brain-stem activity can be obtained in anesthetized animals, provided that temperature and other parameters are maintained within normal physiological limits.

Anesthesia

Recoveries of whole-nerve AP thresholds, amplitudes and tuning curves in gerbils following noise exposure.

The recoveries of whole-nerve action potential (AP) thresholds, AP amplitudes and AP tuning curves in gerbils were monitored following two weeks of exposure to band-pass noise at 85 dBA. Recordings were made by means of electrodes chronically implanted in the subjects' bullas. The noise exposure caused threshold elevations in all of our subjects, with the greatest shifts occurring an octave or more above the 2 kHz upper cutoff frequency of the noise. The magnitudes of the shifts varied greatly (up to 26 dB) across subjects. Thresholds of animals with the smallest initial loss of sensitivity returned to pre-exposure values within 16 days, while those of animals with greater initial losses remained elevated beyond 16 days. AP amplitudes and AP tuning curves (APTCs) were most affected at frequencies where the initial threshold shifts were greatest. At these frequencies AP amplitudes were reduced, and APTCs showed broadened tips, reduced tip-to-tail ratios, and in some cases a shift in the frequency of the tip. These effects did not necessarily reverse with threshold recovery, suggesting that AP amplitudes and AP tuning curves are more sensitive indices of acoustic injury than are AP thresholds.

Action Potentials

Middle latency response: frequency and intensity effects.

Auditory middle latency responses (MLR) and auditory brainstem responses (ABR) were measured with epidural electrodes in unanesthetized gerbils. Response thresholds of simultaneously recorded MLRs and ABRs, and latencies and amplitudes of MLR peaks were analyzed with respect to stimulus intensity (10-80 dB SPL) and frequency (0.5, 1, 2, 4, 8 and 16 kHz). Only minor changes in the latencies of the MLR were associated with increases in stimulus intensity. Changes in latencies were more apparent for waves A and B as compared to wave C, and were significant only at low intensities. Latencies did not change significantly as a function of stimulus frequency. Amplitudes of the MLR were highly variable between animals, particularly waves B and C, and showed complex changes with intensity. In general, wave amplitudes were inversely related to stimulus frequency. The gerbil MLR resembles MLRs recorded under similar conditions in guinea pig, cat, and rat. Some qualitative similarities between gerbil and human MLRs are apparent. Results indicate that the MLR is a less sensitive measure of hearing threshold relative to the fast waves of the ABR at frequencies above 1 kHz. However, clearly defined MLRs are elicited with a wide range of stimulus frequencies. Because the surface recorded MLR reflects activation of central auditory pathways, including the cortex, it may provide an electrophysiological measure which can be utilized to study central components of normal and pathological auditory function.

Acoustic Stimulation

A comparison of brainstem, whole-nerve AP and single-fiber tuning curves in the gerbil: normative data.

Tuning curves were obtained from brainstem responses (BSRs) and whole-nerve action potential (AP) responses of gerbils using a forward masking procedure. These are compared with single-fiber tuning curves of the gerbil. The broadness of the tips, tip-to-tail ratios and the slopes of the high frequency sides of the BSR tuning curves are similar to those of the AP curves for probe frequencies ranging from 1 to 8 kHz. Also, the BSR and AP curves share a number of characteristics with single-fiber tuning curves. These results suggest that, like the AP, components of the BSR can be used to measure frequency selectivity in the periphery of an intact auditory system.

Animals

Cardiopathogenicity of soybean oil and tower rapeseed oil triglycerides when fed to male rats.

The triglycerides of soybean oil were purified by molecular distillation and those of Tower rapeseed oil by molecular distillation and adsorption chromatography. The original oils and the purified triglycerides were incorporated in semisynthetic diets at 20% by weight and fed for 16 weeks to weanling male Sprague-Dawley rats to compare the nutritional and pathological effects of the oils and their triglyceride fractions on rats. The study was carried out at two independent laboratories. No significant differences were observed between the results of the two establishments. The incidence of myocardial lesions was significantly higher in rats fed Tower rapeseed oil than in those fed soybean oil. Purification of the triglycerides by molecular distillation and adsorption chromatography appeared to have no major effect on the incidence of myocardial lesions. This supports our previous findings that the cardiopathogenicity appeared to have no major effect on the incidence of myocardial lesions. This supports our previous findings that the cardiopathogenicity of the test oils to rats resides in the triglycerides of these oils.

Animals

Temporary threshold shifts in humans exposed to octave bands of noise for 16 to 24 hours.

Groups of human subjects were exposed in a diffuse sound field for 16--24 h to an octave-band noise centered at 4, 2, 1, or 0.5 kHz. Sound-pressure levels were varied on different exposure occasions. At specified times during an exposure, the subject was removed from the noise, auditory sensitivity was measured, and the subject was returned to the noise. Temporary threshold shifts (TTS) increased for about 8 h and then reached a plateau or asymptote. The relation between TTS and exposure duration can be described by a simple exponential function with a time constant of 2.1 h. In the frequency region of greatest loss, threshold shifts at asymptote increased about 1.7 dB for every 1 dB increase in the level of the noise above a critical level. Critical levels were empirically estimated to be 74.0 dB SPL at 4 kHz. 78 dB at 2 kHz, and 82 dB at 1 and 0.5 kHz. Except for the noise centered at 4.0 kHz, threshold shifts were maximal about 1/2 octave above the center frequency of the noise. A smaller second maximum was observed also at 7.0 kHz for the noise centered at 2.0 kHz, at 6.0 kHz for the noise centered at 1.0 kHz, and at 5.5 kHz for the noise centered at 0.5 kHz. After termination of the exposure, recovery to within 5 dB of pre-exposure thresholds was achieved within 24 h or less. Recovery can be described by a simple exponential function with a time constant of 7.1 h. The frequency contour defined by critical levels matches almost exactly the frequency contour defined by the E-weighting network.

Adult

Arrhenoblastoma in a mare.

An ovarian neoplasm measuring 10 by 8 by 6 cm was surgically removed from a 14-year-old Appaloosa mare. For 2 years prior to surgery, the mare had manifested marked behavioral changes, becoming aggressive toward other broodmares. Histologically, the tumor was found to be an arrhenoblastoma. Preoperative endocrinologic findings (high serum testosterone and low serum estradiol concentrations) supported the diagnosis.

Aggression