Biomedical subjects

B M Johnstone

Publications and source records attributed to B M Johnstone.

At least 19 recordsLinked to original sources

PubMed1992

Mechanical preprocessing in the mammalian cochlea.

The mammalian cochlea responds with exquisite sensitivity to the small fluctuations in air pressure that make up the stimulus of sound. Moreover, it responds to pressure fluctuations that occur extremely rapidly and that vary over a wide range of intensities--in both cases, to an extent outside the capabilities of unaided nerve fibres. Research performed during the past decade has shown that these properties are dependent on a physiological source of mechanical energy that operates probably within the outer hair cells of the organ of Corti. These cells, which are anatomically and functionally similar to the primary receptor cells, the inner hair cells, are believed to function as a source of mechanical power to assist the mechanical sensitivity of the cochlea, by mechanisms that currently are not understood. Several possible mechanisms have been proposed, but each has limitations that may make it an unsuitable candidate. Recent work has also demonstrated the likely role of mechanoelectrical transduction in outer hair cells in controlling the power source and thereby influencing the sensitivity and amplitude range of the cochlea.

Animals↗

PubMed1991

Preliminary results from a meta-analysis of drinking behavior in multiple longitudinal studies.

This paper introduces the scope and rationale of The Collaborative Alcohol-Related Longitudinal Project and describes the individual longitudinal studies which contribute to this large collaborative project, representing studies from 15 countries. It also serves as an introduction to four reports of the preliminary findings from the project. The project is distinguished by (1) its interdisciplinary research approach which has assembled a multidisciplinary group of scholars to direct and interpret analyses, (2) its use of primary data from multiple longitudinal studies, (3) the parallel analyses of primary data from multiple studies, using comparable measures across studies recorded to a standard format and common analytic model, and (4) its use of meta-analysis to combine results across studies. Its research objectives include determining the cross-study consistency of findings of (1) the incidence and chronicity of drinking patterns and problems, (2) exogeneous factors which initiate and alter drinking careers, (3) socio-behavioral factors measured in childhood and adolescence which predict adult drinking problems, (4) inter-generational biological and social factors which predict adult drinking problems, and (5) aggregate-level factors which account for study differences. The method of sampling of studies from the world's alcohol-related general population longitudinal research is described.

Alcohol Drinking↗

PubMed1991

An integrated approach to meta-analysis in alcohol studies.

The research design and methods utilized by the Collaborative Alcohol-Related Longitudinal Project are described. The project design addresses the critical need to develop procedures to assess the replicability of research results in alcohol studies. Key features of the research plan include: re-analysis of original data from multiple longitudinal studies of drinking behavior in the general population; centralization of all data analyses, developed and implemented by an interdisciplinary core staff; development of the research plan and interpretation of results in co-operation with original investigators of studies included in the project; and use of modeling procedures from meta-analysis to quantify the relative contribution of factors influencing the distribution of effect estimates across studies, including both methodological differences and aggregate level variables. The final section describes statistical methods for meta-analysis used by the project, including procedures for the calculation and combination of estimates of effect magnitude, categorical and continuous modeling procedures for use with effect sizes, and random effects models.

Alcohol Drinking↗

PubMed1991

A meta-analysis of life course variation in drinking.

Meta-analysis combines results from multiple longitudinal studies to describe life course variation by age and sex for quantity of drinking per typical occasion (20 studies) and frequency of drinking during one month (27 studies). There is cross-study heterogeneity for the Time 1 means of the drinking variables blocking for age and sex. Age distributions for the Time 1 means are similar by gender within nations; in the aggregate, males exceed females in the magnitude of drinking. Dramatic shifts in the standardized mean difference (M2-M1) occur among the young; greater homogeneity and moderate change (declines) occur later in life. Implicated in improving cross-study homogeneity for M2-M1 among the young are interval between measurements, nation, Time 1 per capita consumption (PCC), difference in PCC and the Time 1 mean. Lower unstandardized regression coefficients are found for quantity among youth, but are not consistently homogeneous within nations; the association for frequency becomes increasingly stable with increasing age. Nation and interval are implicated in improving homogeneity. Decline in quantity occurs among the old. M2-M1 produces homogeneously higher regressions for groups of the young who increase quantity v. those who do not. Linkage of the group-level and individual-level findings is discussed.

Adolescent↗

PubMed1990

The ototoxic mechanism of cisplatin.

The ototoxic mechanism of cisplatin was investigated. Potentiation of cisplatin ototoxicity by furosemide and amino-oxyacetic acid (AOAA) was observed. Substantial hearing loss in cisplatin-deafened animals was accompanied by normal values of the endocochlear potential and a reduction in the sensitivity of the 2f1-f2 distortion products. The loss in dB of the sensitivity of the distortion products correlated extremely well with the loss of the neural sensitivity in dB. There was also a relationship between the fractional reduction of the low frequency (1000 Hz) microphonic potential and hearing loss in dB. Iontophoresis of cisplatin into scala media resulting in the immediate loss of neural thresholds at the site of iontophoresis. It is concluded that cisplatin caused the hearing loss by blocking OHC transduction channels.

Aminooxyacetic Acid↗

PubMed1990

Absence of tonic activity of the crossed olivocochlear bundle in determining compound action potential thresholds, amplitudes and masking phenomena in anaesthetised guinea pigs with normal hearing sensitivities.

In Nembutal- or Urethane-anaesthetised guinea pigs N1 audiograms and N1 input-output functions were measured as were compound action potential (CAP) tuning curves under forward masking and simultaneous masking conditions. Then the crossed olivocochlear bundle was lesioned at the floor of the fourth ventricle and the cochlear responses were re-measured. There were never any changes in the N1 audiograms, input-output functions, or the CAP tuning curves. Thus, the crossed efferent pathways do not appear to play any tonic role in determining cochlear threshold sensitivities, selectivities or masking phenomena in anaesthetised guinea pigs with normal hearing sensitivities.

Action Potentials↗

PubMed1990

Saturation of outer hair cell receptor currents causes two-tone suppression.

Zwicker [Biol. Cybern. 35, 243-250, (1979); J. Acoust. Soc. Am. 80, 163-176 (1986)] has previously proposed that many nonlinear phenomena in the mammalian cochlea can be explained by saturation of a positive feedback process which enhances mechanical sensitivity, although the site of the nonlinearity producing this saturation has so far remained obscure. In this paper we present evidence suggesting that the nonlinearity of mechano-electrical transduction in the outer hair cells is the dominant nonlinearity producing two-tone suppression in the mammalian cochlea. In particular, we show that: (i) suppression of the extracellular summating potential (SP), recorded from a particular place within the organ of Corti, has characteristics similar to the suppression of activity in the auditory-nerve; (ii) that SP suppression occurs at approximately constant basilar membrane displacement, inferred from the SP iso-response contours; and that (iii) the onset of SP suppression with suppressor tones on the tail of the frequency tuning curve closely parallels the onset of nonlinearity in the local cochlear microphonic. Since previous studies (Patuzzi et al., 1989) have demonstrated that the vibration of the basilar membrane at its characteristic frequency is very sensitive to changes in outer hair cell receptor current, we consider that interference in outer hair cell currents caused by nonlinearity in mechano-electrical transduction is an adequate explanation of two-tone suppression. This requires that outer hair cell receptor currents deviate from linearity at a suppressor tone level below that required to produce a significant DC receptor potential within the inner hair cells, and that the active process within the cochlea is distributed along a local region of the cochlea, basal of the vibration peak.

Acoustic Stimulation↗

PubMed1990

Effects of L-glutamate on auditory afferent activity in view of its proposed excitatory transmitter role in the mammalian cochlea.

This report describes the effects of L-glutamate (Glu) introduced into the perilymph of scala tympani on the spontaneous and tone-evoked activity of guinea pig single primary auditory afferents. Concentrations below 2 mmol/l were in general ineffective, while a concentration of 5 mmol/l caused a marked decrease of the neural activity. At 2 mmol/l, roughly 60% of the Glu-perfusions were effective and produced a variety of changes. The most prominent effect was a reduction of the tone-evoked activity without a change in spontaneous rate. Indeed, in some cells, the tone-evoked activity could be almost totally abolished without affecting the spontaneous activity. More rarely observed was a moderate, generally transient increase of the spontaneous activity which was occasionally followed by a decrease in both tone-evoked and spontaneous firing rate. The increase in firing rate was always small relative to the maximum discharge rate evoked by tone stimuli. Desensitization of the Glu-evoked response without an obvious change in the spontaneous activity was also found. In a few cells Glu caused a reduction of the discharge rate below the spontaneous firing rate during loud tone presentation. Higher Glu doses generally caused a reduction of spontaneous and tone-evoked activity without any sign of a preceding increase. Thus, the effects of Glu in the mammalian cochlea appear to be complex and on balance seem inconsistent with the effects predicted for an excitatory transmitter. The findings argue against the hypothesis that Glu is the afferent transmitter released by inner hair-cells. However, the results do not exclude an involvement of Glu as a neuromodulator or co-transmitter.

Acoustic Stimulation↗

PubMed1989

Contralateral cochlear destruction mediates protection from monoaural loud sound exposures through the crossed olivocochlear bundle.

Destruction of the cochlea contralateral to one subsequently exposed to a high intensity acoustic exposure has been shown to reduce the threshold losses caused by the exposure (Rajan and Johnstone, 1983a). The present study tested this manipulation on a wide variety of exposures of varying intensity and duration and found that the amount by which ipsilateral threshold losses were reduced was related to the amount of threshold losses that would have occurred in the absence of the contralateral manipulation. This loss-related protection is also found when the COCB is electrically stimulated during loud sound exposures (Rajan, 1988b; Rajan and Johnstone, 1988b). When the COCB was lesioned at the floor of the fourth ventricle contralateral cochlea destruction no longer protected the test cochlea, confirming that the crossed cochlear protection was exercised through the COCB. The contralateral manipulation did not appear to directly activate the COCB but may have acted in a facilitatory manner on the COCB, allowing activation only when a sufficiently high level exposure was subsequently presented ipsilaterally: a variety of responses at the ipsilateral cochlea and at the brainstem, remeasured after contralateral cochlear destruction and prior to an ipsilateral loud sound exposure, were found to be unaltered, although the TTS to the subsequent exposure was significantly reduced.

Animals↗

PubMed1989

The origin of the low-frequency microphonic in the first cochlear turn of guinea-pig.

Low-frequency microphonic potentials (100 Hz to 2000 Hz) have been measured in the first turn of the guinea pig cochlea before and after a variety of manipulations of the cochlea. These included ablation of the apical turns, iontophoresis of streptomycin, dc current injection into the first turn, acoustic trauma and two-tone interference with pure tones. These manipulations indicate that the low-frequency microphonic measured in the first turn and at the round window is generated predominantly by the hair cells of this region. It is a convenient and relatively uncomplicated indicator of the integrity of the mechano-electrical transduction process of these cells.

Acoustic Stimulation↗

PubMed1989

Changes in cochlear microphonic and neural sensitivity produced by acoustic trauma.

The low-frequency (200 Hz) microphonic potentials at the round window and in the organ of Corti of the first turn of the guinea pig cochlea have been measured before and after acoustic overstimulation. Reductions in the amplitude of this microphonic after loud sound are highly correlated with neural threshold elevation in this region. The fall in the microphonic amplitude appears due to an inactivation of mechano-electrical transduction channels at the apex of the outer hair cells into a closed state. These results are consistent with the idea that the current through the outer hair cells controls the mechanical sensitivity of the organ of Corti, and that the temporary loss of mechanical and neural sensitivity following loud sound is due to a simple inactivation of the mechano-electrical transduction channels.

Action Potentials↗

PubMed1989

Outer hair cell receptor current and sensorineural hearing loss.

It is argued in this paper that many nonlinear phenomena in audition and many types of sensorineural hearing loss can be explained by a disruption of the mechano-electrical transduction process at the apex of the outer hair cells. This is done using experimental data and a simple model of the active role of outer hair cells in cochlear mechanics based on our previous experiments with acoustic trauma. The causes of sensorineural loss addressed include acoustic trauma, aminoglycoside ototoxicity, intoxication with loop diuretics, hypoxia and Meniere's disease. The nonlinear phenomena discussed include loudness compression, two-tone suppression and modulation of cochlear sensitivity by very low-frequency tones. In every case considered the reduction in neural sensitivity was related to the reduction in outer hair cell receptor current in a quantitatively similar way. We conclude that the link is causal.

Animals↗

PubMed1989

Stimulus-related potassium changes in the organ of Corti of guinea-pig.

1. Potassium concentration was measured with double-barrelled K+-selective microelectrodes within the organ of Corti in the first turn of the guinea-pig cochlea. 2. Penetration of the electrode from scala tympani through the basilar membrane was accompanied by an increase in K+ resting level from 3.0 mmol/l in perilymph to 3.4 mmol/l in cortilymph (n = 8). K+ resting level was not significantly different in various extracellular regions of the organ of Corti. On penetration of the cuticular plate, the K+ level reached 140 mmol/l simultaneously with the occurrence of a +80 mV endocochlear potential. Impalement of hair cells and supporting cells was accompanied by an increase in K+ level, but intracellular K+ level was not systematically measured. 3. Stimulation with pure tones over the frequency range 500 Hz to 25 kHz produced changes in the K+ level in the organ of Corti. The magnitude of these changes was dependent on stimulus frequency and intensity. At high sound intensities the K+ level in the tunnel of Corti could increase by typically 1 mmol/l, while a maximum increase of 3 mmol/l with respect to the resting level was observed immediately adjacent to inner hair cells. 4. During brief exposures to moderate intensity, pure tone acoustic stimulation (10 s, less than 80 dB SPL (sound pressure level] of frequency 4 kHz or greater the K+ level in the extracellular fluid of the organ of Corti rose monotonically to a steady peak level. On cessation of the stimulus the K+ level fell monotonically with a time constant of about 2 s to a level close to the pre-stimulus level. In some cases this level was slightly above the pre-stimulus level. 5. For brief exposures to moderate intensity sound (10 s, less than 80 dB SPL) the extracellular potential in the organ of Corti became more positive. The amplitude of this sound-evoked change adapted during stimulation to a level approximately one-fifth of its initial value. Upon cessation of the stimulus the potential fell transiently below its pre-stimulus level, before recovering to that level. The time constant of these changes was between 2 and 3 s. 6. Iso-response tuning curves for the sound-evoked elevation in K+ level in the organ of Corti in animals in good condition were similar to iso-rate tuning curves for primary afferent fibres reported previously.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗

PubMed1988

Binaural acoustic stimulation exercises protective effects at the cochlea that mimic the effects of electrical stimulation of an auditory efferent pathway.

Low-level acoustic stimulation of one (contralateral) ear reduced the neural desensitization caused by a simultaneous loud sound exposure in the other (ipsilateral) ear in a loss-related manner. Greatest reductions in the temporary threshold shifts (TTS) in the exposed ear were obtained when the exposure would have caused large amounts of TTS. Low-level exposures (reduced intensity or duration of exposure) which caused low levels of TTS, from which the cochlea could recover relatively quickly, were not affected by the contralateral stimulus. Intermediate levels of TTS showed intermediate levels of reduction for the same contralateral acoustic stimulus. These effects were similar to effects previously demonstrated with electrical stimulation of an efferent pathway to the cochlea, the crossed olivocochlear bundle (COCB); lesioning the COCB prevented the contralateral stimulus from having any effect on TTS due to an ipsilateral exposure. Like COCB stimulation, the contralateral acoustic stimulus had tonic effects, so that reductions in ipsilateral TTS could be obtained even when the contralateral stimulus was presented 5 min before the ipsilateral exposure. With 10 min delay no effect on TTS occurred. The contralateral stimulus did not appear to cause any changes in responses in the ipsilateral cochlea prior to the loud sound exposure. These results are discussed as indicating an interaction between the two inputs at a central locus, leading to activation of the COCB fibres to the cochlea exposed to the loud sound.

Acoustic Stimulation↗

PubMed1988

Effect of spider venom on cochlear nerve activity consistent with glutamatergic transmission at hair cell-afferent dendrite synapse.

Venom from the spider Argiope trifasciata, a highly specific blocker of the ionic channels associated with invertebrate glutamatergic receptors, was perfused through scala tympani of the basal turn of the pig cochlea. Its effect on spontaneous and driven activity of single afferent neurons was studied. 0.1 U/ml spider venom altered the maximum driven activity without an effect on spontaneous activity. 1 U/ml spider venom suppressed both spontaneous and driven activity. These findings are consistent with the hypothesis that L-glutamate is the neurotransmitter of the synapse between inner hair cells and primary auditory afferent neurons. The results also suggest that the differences in spontaneous activity between neurons may originate in variations in neurotransmitter release.

Animals↗

PubMed1988

Post-stimulatory effects of direct current stimulation of the cochlea on auditory nerve activity.

Glass micro-electrode recordings from the spiral ganglion of the basal turn of the guinea pig cochlea have been obtained before, during and after negative (cathodic) current injection into scala tympani. Electrical stimulation with currents between 100 microA and 900 microA produced a marked increase in firing rate of the afferent neurons for the first 3 min of electrical stimulation. This was followed by a fall in firing rate to rates near or below the pre-stimulatory spontaneous rate if stimulation continued. Continuous electrical stimulation lasting 5 or 10 min reduced neural sensitivity to acoustic stimulation. Although threshold elevation was greatest for sound frequencies near the characteristic frequency of each neuron, thresholds could also be elevated at lower frequencies on the tail of the frequency-threshold tuning curve. After electrical stimulation a fall in the amplitude of the low-frequency microphonic recorded at the round window was also observed, indicating a disruption of the outer hair cell transduction. These effects were highly localized in the basal turn near the site of current injection, and were not associated with any significant structural changes in the organ of Corti, except after stimulation with very high current intensities.

Acoustic Stimulation↗

PubMed1988

Modulation transfer function of efferent neurones in the guinea pig cochlea.

The dynamic properties of single olivocochlear efferent neurones in the guinea pig cochlea were examined using sinusoidally amplitude modulated (AM) pure tones. The neural discharge, when displayed as a cyclic histogram, clearly followed the rapid fluctuations in the continuous input sound. Modulation transfer functions (MTFs) were constructed and in most cases showed a peak in the modulation response (MR) at a modulation frequency (MF) of 100 Hz. At this frequency a gain of as much as 12 dB was evident relative to the 30% modulated input signal. In 24% of neurones however, a large MR was present even at low MFs. This plurality of MTFs may be the result of recorded neurones emanating from a variety of cell bodies of origin. Efferent group delays (mean of 8.2 +/- 1.0 ms) were shorter and more tightly distributed than the minimum onset latency measurements (mean of 24.2 +/- 12.5) made on the same neurones. It seems evident that a post-synaptic potential build is required from the onset of a stimulus to the first spike discharge. This may occur within a single afferent-interneurone(s)-efferent reflex arc. Among a variety of alternative explanations, the observation is consistent with the notion that the olivocochlear neurones receive facilitatory input from higher centres, which is suppressed under barbiturate anaesthesia. Continuous AM signals may allow post-synaptic build up and eliminate the dependence on this higher input and hence yield a short group delay.

Acoustic Stimulation↗

PubMed1988

Electrical stimulation of cochlear efferents at the round window reduces auditory desensitization in guinea pigs. I. Dependence on electrical stimulation parameters.

Electrical stimulation at the round window with pulsed short trains has been shown to elicit classical efferent effects on N1 amplitudes at the cochlea. This report demonstrates that round window stimulation as a continuous burst can reduce temporary threshold shifts (TTS) caused by a simultaneous monaural loud sound exposure. This result is similar to recent reports that stimulation of the crossed olivocochlear bundle (COCB) at the floor of the fourth ventricle can reduce TTS. Like COCB stimulation at the brainstem, the effect of round window stimulation could be abolished by strychnine, with a time course paralleling the blocking action of strychnine on the traditional COCB effects of pulsed short trains on N1 amplitudes. This report also established parameters for optimal effects of the round window stimulus and found them to be similar to the optimal parameters for the effects of brainstem stimulation on TTS. Tonic effects on TTS were also observed, with reductions in TTS being obtained as much as 7 min after a 1 min-long round window stimulus. Such tonic effects did not appear to be due to persistent effects at the cochlea but were suggested to be due to a long term resetting of some central site activated by antidromic stimulation from the round window.

Animals↗