Biomedical subjects

J J Guinan

Publications and source records attributed to J J Guinan.

At least 19 recordsLinked to original sources

PubMed2006

Efferent-mediated control of basilar membrane motion.

Medial olivocochlear efferent (MOCE) neurones innervate the outer hair cells (OHCs) of the mammalian cochlea, and convey signals that are capable of controlling the sensitivity of the peripheral auditory system in a frequency-specific manner. Recent methodological developments have allowed the effects of the MOCE system to be observed in vivo at the level of the basilar membrane (BM). These observations have confirmed earlier theories that at least some of the MOCE's effects are mediated via the cochlea's mechanics, with the OHCs acting as the mechanical effectors. However, the new observations have also provided some unexpected twists: apparently, the MOCEs can enhance the BM's responses to some sounds while inhibiting its responses to others, and they can alter the BM's response to a single sound using at least two separate mechanisms. Such observations put new constraints on the way in which the cochlea's mechanics, and the OHCs in particular, are thought to operate.

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PubMed2004

Otoacoustic emissions without somatic motility: can stereocilia mechanics drive the mammalian cochlea?

Distortion product otoacoustic emissions (DPOAEs) evoked by low-level tones are a sensitive indicator of outer hair cell (OHC) function. High-level DPOAEs are less vulnerable to cochlear insult, and their dependence on the OHC function is more controversial. Here, the mechanism underlying high-level DPOAE generation is addressed using a mutant mouse line lacking prestin, the molecular motor driving OHC somatic motility, required for cochlear amplification. With prestin deletion, attenuated DPOAEs were measurable at high sound levels. DPOAE thresholds were shifted by approximately 50 dB, matching the loss of cochlear amplifier gain measured in compound action potentials. In contrast, at high sound levels, distortion products in the cochlear microphonic (CM) of mutants were not decreased re wildtypes (expressed re CM at the primaries). Distortion products in both CM and otoacoustic emissions disappeared rapidly after death. The results show that OHC somatic motility is not necessary for the production of DPOAEs at high SPLs. They also suggest that the small, physiologically vulnerable DPOAE that remains without prestin-based motility is due directly to the mechanical nonlinearity associated with stereociliary transduction, and that this stereocilia mechanical nonlinearity is robustly coupled to the motion of the cochlear partition to the extent that it can drive the middle ear.

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PubMed2003

Responses of medial olivocochlear neurons. Specifying the central pathways of the medial olivocochlear reflex.

Medial olivocochlear (MOC) neurons project to outer hair cells (OHC), forming the efferent arm of a reflex that affects sound processing and offers protection from acoustic overstimulation. The central pathways that trigger the MOC reflex in response to sound are poorly understood. Insight into these pathways can be obtained by examining the responses of single MOC neurons recorded from anesthetized guinea pigs. Response latencies of MOC neurons are as short as 5 ms. This latency is consistent with the idea that type I, but not type II, auditory-nerve fibers provide the major inputs to the reflex interneurons in the cochlear nucleus. This short latency also implies that the cochlear-nucleus interneurons have rapidly conducting axons. In the cochlear nucleus, lesions of the posteroventral subdivision (PVCN), but not the anteroventral (AVCN) or dorsal (DCN) subdivisions, produce permanent disruption of the MOC reflex, based on a metric of adaptation of the distortion-product otoacoustic emission (DPOAE). This finding supports earlier anatomical results demonstrating that some PVCN neurons project to MOC neurons. Within the PVCN, there are two general types of units when classified according to poststimulus time histograms: onset units and chopper units. The MOC response is sustained and cannot be produced solely by inputs having an onset pattern. The MOC reflex interneurons are thus likely to be chopper units of PVCN. Also supporting this conclusion, chopper units and MOC neurons both have sharp frequency tuning. Thus, the most likely pathway for the sound-evoked MOC reflex begins with the responses of hair cells, proceeds with type I auditory-nerve fibers, PVCN chopper units, and MOC neurons, and ends with the MOC terminations on OHC.

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PubMed2003

Separate mechanical processes underlie fast and slow effects of medial olivocochlear efferent activity.

Sound-evoked vibrations of the basilar membrane (BM) in anaesthetised guinea-pigs are shown to be affected over two distinct time scales by electrical stimulation of the medial olivocochlear efferent system: one is fast (10-100 ms), the other much slower (10-100 s). For low and moderate level tones near the BM's characteristic frequency, both fast and slow effects inhibited BM motion. However, fast inhibition was accompanied by phase leads, while slow inhibition was accompanied by phase lags. These findings are consistent with a hypothesis that both fast and slow effects decrease sound amplification in the cochlea. However, the opposing directions of the phase changes indicate that separate mechanical processes must underlie fast and slow effects. One plausible interpretation of these findings is that efferent slow effects are caused by outer-hair-cell stiffness decreases, while efferent fast effects are caused by reductions in 'negative damping'.

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PubMed2000

Auditory-nerve-fiber responses to high-level clicks: interference patterns indicate that excitation is due to the combination of multiple drives.

There has been no systematic study of auditory-nerve-fiber (ANF) responses to high-level clicks despite the advantages of clicks in revealing the natural resonances of a system. Cat single ANFs were studied using clicks up to 120 dB pSPL. Peri-stimulus-time (PST) histograms of responses were corrected for refractory effects, and compound PST (cPST) histograms were formed from rarefaction- and condensation-click PSTs. At low levels the responses followed the classic picture with each cPST appearing to be from a single resonant system followed by low-pass filtering that reduces high-frequency synchrony. In fibers across all characteristic frequencies, there were significantly different patterns at high click levels including several nonclassic features and "phase reversals," i.e., a peak in the rarefaction-click PST at low levels was replaced at high levels by a peak at the same latency in the condensation-click PST. There were two separate regions of nonclassic features and phase reversals, which indicates that auditory-nerve fibers are excited by the combination at some stage in the cochlea of at least three excitation drives derived from the acoustic stimulus. These data support the interpretation that the cochlear partition vibrates in multiple resonant modes with each mode producing one excitation drive and that the mix of modes varies with sound level.

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PubMed2000

Medial efferent effects on auditory-nerve responses to tail-frequency tones II: alteration of phase.

It is often assumed that at frequencies in the tuning-curve tail there is a passive, constant coupling of basilar-membrane motion to inner hair cell (IHC) stereocilia. This paper shows changes in the phase of auditory-nerve-fiber (ANF) responses to tail-frequency tones and calls into question whether basilar-membrane-to-IHC coupling is constant. In cat ANFs with characteristic frequencies > or = 10 kHz, efferent effects on the phase of ANF responses to tail-frequency tones were measured. Efferent stimulation caused substantial changes in ANF phase (deltaphi) (range -80 degrees to +60 degrees, average -15 degrees, a phase lag) with the largest changes at sound levels near threshold and 3-4 octaves below characteristic frequency (CF). At these tail frequencies, efferent stimulation had much less effect on the phase of the cochlear microphonic (CM) than on ANF phase. Thus, since CM is synchronous with basilar-membrane motion for low-frequency stimuli in the cochlear base, the efferent-induced change in ANF phase is unlikely to be due entirely to a change in basilar-membrane phase. At tail frequencies, ANF phase changed with sound level (often by 90 degrees-180 degrees) and the deltaphi from a fiber was positively correlated with the slope of its phase-versus-sound-level function at the same frequency, as if deltaphi were caused by a 2-4 dB increase in sound level. This correlation suggests that the processes that produce the change in ANF phase with sound level at tail frequencies are also involved in producing deltaphi. It is hypothesized that both efferent stimulation and increases in sound level produce similar phase changes because they both produce a similar mix of cochlear vibrational modes.

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PubMed2000

Lateralized tinnitus studied with functional magnetic resonance imaging: abnormal inferior colliculus activation.

Tinnitus, the perception of sound in the absence of external stimuli, is a common and often disturbing symptom that is not understood physiologically. This paper presents an approach for using functional magnetic resonance imaging (fMRI) to investigate the physiology of tinnitus and demonstrates that the approach is effective in revealing tinnitus-related abnormalities in brain function. Our approach as applied here included 1) using a masking noise stimulus to change tinnitus loudness and examining the inferior colliculus (IC) for corresponding changes in activity, 2) separately considering subpopulations with particular tinnitus characteristics, in this case tinnitus lateralized to one ear, 3) controlling for intersubject differences in hearing loss by considering only subjects with normal or near-normal audiograms, and 4) tailoring the experimental design to the characteristics of the tinnitus subpopulation under study. For lateralized tinnitus subjects, we hypothesized that sound-evoked activation would be abnormally asymmetric because of the asymmetry of the tinnitus percept. This was tested using two reference groups for comparison: nontinnitus subjects and nonlateralized tinnitus subjects. Binaural noise produced abnormally asymmetric IC activation in every lateralized tinnitus subject (n = 4). In reference subjects (n = 9), activation (i.e., percent change in image signal) in the right versus left IC did not differ significantly. Compared with reference subjects, lateralized tinnitus subjects showed abnormally low percent signal change in the IC contralateral, but not ipsilateral, to the tinnitus percept. Consequently, activation asymmetry (i.e., the ratio of percent signal change in the IC ipsilateral versus contralateral to the tinnitus percept) was significantly greater in lateralized tinnitus subjects as compared with reference subjects. Monaural noise also produced abnormally asymmetric IC activation in lateralized tinnitus subjects. Two possible models are presented to explain why IC activation was abnormally low contralateral to the tinnitus percept in lateralized tinnitus subjects. Both assume that the percept is associated with abnormally high ("tinnitus-related") neural activity in the contralateral IC. Additionally, they assume that either 1) additional activity evoked by sound was limited by saturation or 2) sound stimulation reduced the level of tinnitus-related activity as it reduced the loudness of (i.e., masked) the tinnitus percept. In summary, this work demonstrates that fMRI can provide objective measures of lateralized tinnitus and tinnitus-related activation can be interpreted at a neural level.

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PubMed1999

Motoneuron axon distribution in the cat stapedius muscle.

Stapedius-motoneuron cell bodies in the brainstem are spatially organized according to their acoustic response laterality, as demonstrated by intracellular labeling of physiologically identified motoneurons [Vacher et al., 1989. J. Comp. Neurol. 289, 401-415]. To determine whether a similar functional spatial segregation is present in the muscle, we traced physiologically identified, labeled axons into the stapedius muscle. Ten labeled axons were visible in the facial nerve and five could be traced to endplates within the muscle. These five axons had 39 observed branches (others may have been missed). This indicates an average innervation ratio (> or = 7.8) which is much higher than that obtained from previous estimates of the numbers of stapedius motoneurons and muscle fibers in the cat. One well-labeled stapedius motor axon innervated only a single muscle fiber. In contrast, two labeled axons had over 10 endings and innervated muscle fibers spread over wide areas in the muscle. Two of the axons branched and coursed through two primary stapedius fascicles, indicating that the muscle zones innervated by different primary fascicles are not functionally segregated. In another series of experiments, retrograde tracers were deposited in individual primary nerve fascicles. In every case, labeled stapedius-motoneuron cell bodies were found in each of the physiologically identified stapedius-motoneuron regions in the brainstem. These observations suggest there is little, if any, functional spatial segregation based on separate muscle compartments in the stapedius muscle, despite there being functional spatial segregation in the stapedius-motoneuron pool centrally.

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PubMed1999

Evoked otoacoustic emissions arise by two fundamentally different mechanisms: a taxonomy for mammalian OAEs.

Otoacoustic emissions (OAEs) of all types are widely assumed to arise by a common mechanism: nonlinear electromechanical distortion within the cochlea. In this view, both stimulus-frequency (SFOAEs) and distortion-product emissions (DPOAEs) arise because nonlinearities in the mechanics act as "sources" of backward-traveling waves. This unified picture is tested by analyzing measurements of emission phase using a simple phenomenological description of the nonlinear re-emission process. The analysis framework is independent of the detailed form of the emission sources and the nonlinearities that produce them. The analysis demonstrates that the common assumption that SFOAEs originate by nonlinear distortion requires that SFOAE phase be essentially independent of frequency, in striking contradiction with experiment. This contradiction implies that evoked otoacoustic emissions arise by two fundamentally different mechanisms within the cochlea. These two mechanisms (linear reflection versus nonlinear distortion) are described and two broad classes of emissions--reflection-source and distortion-source emissions--are distinguished based on the mechanisms of their generation. The implications of this OAE taxonomy for the measurement, interpretation, and clinical use of otoacoustic emissions as noninvasive probes of cochlear function are discussed.

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PubMed1999

Medial efferent effects on auditory-nerve responses to tail-frequency tones. I. Rate reduction.

One way medial efferents are thought to inhibit responses of auditory-nerve fibers (ANFs) is by reducing the gain of the cochlear amplifier thereby reducing motion of the basilar membrane. If this is the only mechanism of medial efferent inhibition, then medial efferents would not be expected to inhibit responses where the cochlear amplifier has little effect, i.e., at sound frequencies in the tails of tuning curves. Inhibition at tail frequencies was tested for by obtaining randomized rate-level functions from cat ANFs with high characteristic frequencies (CF > or = 5 kHz), stimulated with tones two or more octaves below CF. It was found that electrical stimulation of medial efferents can indeed inhibit ANF responses to tail-frequency tones. The amplitude of efferent inhibition depended on both sound level (largest near to threshold) and frequency (largest two to three octaves below CF). On average, inhibition of high-CF ANFs responding to 1 kHz tones was around 5 dB. Although an efferent reduction of basilar-membrane motion cannot be ruled out as the mechanism producing the inhibition of ANF responses to tail frequency tones, it seems more likely that efferents produce this effect by changing the micromechanics of the cochlear partition.

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PubMed1997

Growth rate of simultaneous masking in cat auditory-nerve fibers: relationship to the growth of basilar-membrane motion and the origin of two-tone suppression.

Although many aspects of the mechanisms by which low-frequency sounds exert their powerful masking on responses to high-frequency sounds are well documented and understood, there are few data on the growth of masking for signal frequencies near, but not necessarily at, auditory-nerve-fiber characteristic frequency (CF). Masking of responses to 6- or 8-kHz tones by a continuous 300-Hz band of noise centered at 500 Hz was measured in single auditory-nerve fibers with various CFs. The growth rate of maskings averaged approximately 2 dB/dB, was typically largest for tones about 10% above fiber CF, and decreased at higher and lower frequencies. This pattern of masking versus frequency relative to CF resembles the pattern of compression of the growth of basilar membrane motion versus frequency at a fixed cochlear place. This correspondence supports the hypothesis that the high growth rate of masking by low-frequency sounds is due to the same mechanisms which produce the compression in the growth of basilar membrane motion.

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PubMed1997

Effects of stapedius-muscle contractions on the masking of auditory-nerve responses.

There has been little exploration of the mechanisms by which stapedius muscle contractions reduce the masking of responses to high-frequency sounds by low-frequency sounds. To fill this gap in knowledge, controlled stapedius contractions were elicited with direct shocks in anesthetized cats, and measurements were made of the effects of these contractions on the masking of single auditory-nerve fibers and on the attenuation of middle-ear transmission. The results show that the stapedius-induced reductions of masking can be much larger than the attenuations of low-frequency sound. With a 300-Hz band of masking noise centered at 500 Hz, and signal tones at 6 or 8 kHz, unmasking effects over 40 dB were observed for sounds 100 dB SPL or less. The data suggest that much larger unmasking might occur. The observed unmasking can be explained completely by a linear stapedius-induced attenuation of sound transmission through the middle ear and a nonlinear growth rate of masking for auditory-nerve fibers. No central effects are required. It is argued that the reduction of the upward spread of masking is probably one of the most important functions of the stapedius muscle.

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PubMed1997

Sound-evoked activity in primary afferent neurons of a mammalian vestibular system.

HYPOTHESIS: Some primary vestibular afferents in the cat respond to sound at moderately intense sound levels. BACKGROUND: In fish and amphibians, parts of the vestibular apparatus are involved in audition. The possibility was explored that the vestibular system in mammals is also acoustically responsive. METHODS: Microelectrodes were used to record from single afferent fibers in the inferior vestibular nerve of the cat; some acoustically responsive fibers were labeled intracellularly with biocytin. RESULTS: Vestibular afferents with regular spontaneous activity were unresponsive to sound, whereas a sizable fraction of vestibular afferents with irregular activity were acoustically responsive. Labeling experiments demonstrated that acoustically responsive afferents innervate the saccule, have cell bodies in Scarpa's ganglion, and project to central regions both inside and outside the traditional boundaries of the vestibular nuclei. Acoustically responsive vestibular afferents responded to sound with shorter latencies than cochlear afferents but had higher thresholds (> 90 dB sound pressure level) and responded only in the range 0.1-3.0 kHz. In contrast to cochlear afferents, efferent stimulation excited background activity and proportionately increased sound-evoked responses in these vestibular afferents, that is, there was centrally mediated enhancement of gain (gain = spike-rate/motion). CONCLUSIONS: The evolutionary conservation of a saccular auditory pathway in mammals suggests that it confers survival advantages. Recent evidence suggests that acoustically responsive saccular afferents trigger acoustic reflexes of the sternocleidomastoid muscle, and hence measurement of such reflexes may provide a relatively simple test for saccular dysfunction.

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PubMed1996

Generators of the brainstem auditory evoked potential in cat. I. An experimental approach to their identification.

This paper is the first in a series aimed at identifying the cellular generators of the brainstem auditory evoked potential (BAEP) in cats. The approach involves (1) developing experimental procedures for making small selective lesions and determining the corresponding changes in BAEP waveforms, (2) identifying brainstem regions involved in BAEP generation by examining the effects of lesions on the BAEP and (3) identifying specific cell populations involved by combining the lesion results with electrophysiological and anatomical information from other kinds of studies. We created lesions in the lower brainstem by injecting kainic acid which is generally toxic for neuronal cell bodies but not for axons and terminals. This first paper describes the justifications for using kainic acid, explains the associated problems, and develops a methodology that addresses the main difficulties. The issues and aspects of the specific methods are generally applicable to physiological and anatomical studies using any neurotoxin, as well as to the present BAEP study. The methods chosen involved (1) measuring the BAEP at regular intervals until it reached a post-injection steady state and perfusing the animals with fixative shortly after the last BAEP recordings were made, (2) using objective criteria to distinguish injection-related BAEP changes from unrelated ones, (3) making control injections to identify effects not due to kainic acid toxicity, (4) verifying the anatomical and functional integrity of axons in lesioned regions, and (5) examining injected brainstems microscopically for cell loss and cellular abnormalities indicating dysfunction. This combination of methods enabled us to identify BAEP changes which are clearly correlated with lesion locations.

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PubMed1996

Generators of the brainstem auditory evoked potential in cat. II. Correlating lesion sites with waveform changes.

Brainstem regions involved in generating the brainstem auditory evoked potential (BAEP) were identified by examining the effects of lesions on the click-evoked BAEP in cats. An excitotoxin, kainic acid, was injected into various parts of the cochlear nucleus (CN) or into the superior olivary complex (SOC). The locations of the resulting lesions were correlated with the changes produced in the various extrema of the BAEP waveforms. The results indicate that: (1) the earliest BAEP extrema (P1, N1 (recorded between vertex and the earbar ipsilateral to the stimulus) and P1a, P1b, (vertex to contralateral earbar)) are generated by cells with somata peripheral to the CN; (2) P2 is primarily generated by posterior anteroventral CN (AVCNp) and anterior posteroventral CN (PVCNa) cells; (3) SOC, anterior anteroventral CN (AVCNa), AVCNp, and PVCNa cells are involved in generating P3; (4) AVCNa cells are the main CN cells involved in P4, N4, and P5 generation; (5) both ipsilateral and contralateral SOC cells have a role in generating monaurally evoked P4 and P5; and (6) P5 is generated by cells with characteristic frequencies below 10 kHz. From (2) and (4), it is clear that P2 and P4-P5 are generated by cells in distinct, parallel pathways.

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PubMed1996

Olivocochlear reflex assays: effects of contralateral sound on compound action potentials versus ear-canal distortion products.

The strength of the olivocochlear reflex has been assayed by comparing ipsilateral cochlear responses with and without contralateral sound. In humans, ipsilateral cochlear responses have usually been inferred by measuring otoacoustic emissions (OAEs), whereas, in animal work, they have been assessed by measuring compound action potentials (CAPs). Thus reports that the reflex strength is smaller in humans than in animals cannot be interpreted until the differences between the two tests are better understood. The present study directly compares reflex assays using distortion-product (DP) OAE and CAP measures in the same animals. For ipsilateral frequencies of 2-8 kHz and levels from 25 to 80 dB SPL, efferent reflex strength was computed from the CAP or DPOAE amplitude-versus-level curves measured with and without contralateral noise. The "effective attenuation" produced by efferent activation was, with few exceptions, greater when measured with the CAP than with the DPOAE assay. Differences between the two measures increased as frequency increased, with differences as large as 10 dB observed. These results, coupled with previous measurements on humans and animals, suggest that the efferent reflex is at least as strong in humans as has been shown in animal experiments.

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PubMed1996

The ipsilaterally evoked olivocochlear reflex causes rapid adaptation of the 2f1-f2 distortion product otoacoustic emission.

The onset behavior of the distortion product otoacoustic emission (DPOAE) at 2f1-f2 in anesthetized cats was measured with temporal resolution finer than 70 ms. The amplitude of the DPOAE adapts after onset of the primary tones by as much as 6 dB for monaural stimulation and 10 dB when the primaries are presented binaurally. DPOAE adaptation consists of a large, rapid component, with a time constant of roughly 100 ms, and a small, slower component with a time constant of roughly 1000 ms. The rapid component disappears when only the crossed olivocochlear bundle (OCB) is cut, whereas the slow adaptation persists after complete OCB section. The loss of rapid adaptation upon OC section is accompanied by a concomitant increase in the steady-state amplitude of the DPOAE. Thus an intact OC reflex can significantly alter DPOAEs obtained during routine measurement. Rapid adaptation of the monaurally evoked 2f1-f2 DPOAE is probably mediated by reflex activity in ipsilaterally responsive OC neurons innervating outer hair cells. The effects of this ipsilateral reflex on DPOAE amplitudes are typically twice as large as those of the contralateral reflex, presumably because there are twice as many ipsilaterally responsive OC neurons. Tests for the ipsilateral OC reflex based on the phenomenon of rapid adaptation should be both feasible and useful in human subjects.

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PubMed1996

Medial efferent inhibition produces the largest equivalent attenuations at moderate to high sound levels in cat auditory-nerve fibers.

Previous work has shown that medial efferents can inhibit responses of auditory-nerve fibers to high-level sounds and that fibers with low spontaneous rates (SRs) are inhibited most. However, quantitative interpretation of these data is made difficult by effects of adaptation. To minimize systematic differences in adaptation, efferent inhibition was measured with a randomized presentation of both sound level and efferent stimulation. In anesthetized cats, efferents were stimulated with 200/s shocks and auditory-nerve-fiber responses were recorded for tone bursts (0-100 dB SPL, 5-dB steps) at their characteristic frequencies. Below 50 dB SPL, efferent inhibition (measured as equivalent attenuation) was similar for all fibers with similar CFs in the same cat. At 45-75 dB SPL, low-SR and medium-SR fibers often showed much larger inhibition, and substantial inhibition even at 100 dB SPL. Expressed as a fractional decrease in rate, at 90-100 dB SPL the inhibition was 0%, 6%, and 13% for high-, medium-, and low-SR fibers (differences statistically significant). Finding the largest equivalent attenuations at 45-75 dB SPL does not fit with the hypothesis that medial-efferent inhibition is due solely to a reduction of basilar-membrane motion. The large attenuations, some over 50 dB, indicate that medial efferent inhibition is more potent than previously reported.

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