John Guinan - Academia.edu (original) (raw)

Papers by John Guinan

Nucleation and Atmospheric Aerosols, 2011

Apical auditory nerve (AN) fibers show two click-response regions that are both strongly inhibite... more Apical auditory nerve (AN) fibers show two click-response regions that are both strongly inhibited by medial olivocochlear (MOC) efferents: (1) ringing responses from low-level (LL) clicks that are thought to be enhanced by a "cochlear amplifier," and (2) AN initial peak (ANIPr) responses from moderate-to-high level (~70-100 dB pSPL) rarefaction clicks. Since MOC fibers synapse and act on outer hair cells (OHCs), the MOC inhibition of these responses indicates that OHC processes are heavily involved in the production of both LL and ANIPr responses. Using AN recordings in anesthetized cats, we explored the role of OHC stereocilia position in the production of these click-response regions by presenting rarefaction clicks at different phases of 50 Hz, 70-110 dB SPL bias tones. Bias effects on LL responses followed the traditional biasing pattern of twice-abias-tone-cycle suppression with more suppression at one phase than the other. This suppression is attributable to the bias tone moving the OHC stereocilia toward low-slope, saturation regions of the mechano-electric transduction function with the rest position being closer to one saturation region. A somewhat similar pattern was found for ANIPr responses except that the bias phases of the largest suppressions were different in ANIPr versus LL responses, usually by ~180 degrees. The data are consistent with the LL and ANIPr responses both being due to active processes in OHCs that are controlled by OHC stereocilia position. The different phases of the LL and ANIPr suppressions indicate that different mechanisms, and perhaps different vibration patterns in the organ of Corti, are involved in the production of LL and ANIPr responses.

Hearing Research, Nov 1, 2016

We used low-frequency "bias" tones (BT's) to explore whether click and tone responses are affecte... more We used low-frequency "bias" tones (BT's) to explore whether click and tone responses are affected in the same way by cochlear active processes. In nonlinear systems the responses to clicks are not always simply related to the responses to tones. Cochlear amplifier gain depends on the incremental slope of the outer-hair-cell (OHC) stereocilia mechano-electric transductance (MET) function. BTs transiently change the operating-point of OHC MET channels and can suppress cochlear-amplifier gain by pushing OHC METs into low-slope saturation regions. BT effects on single auditory-nerve (AN) fibers have been studied on tone responses but not on click responses. We recorded from AN fibers in anesthetized cats and compared tone and click responses using 50 Hz BTs at 70-120 dB SPL to manipulate OHC stereocilia position. BTs can also excite and thereby obscure the BT suppression. We measured AN-fiber response synchrony to BTs alone so that we could exclude suppression measurements when the BT synchrony might obscure the suppression. BT suppression of low-level tone and click responses followed the traditional pattern of twice-a-BT-cycle suppression with more suppression at one phase than the other. The major suppression phases of most fibers were tightly grouped with little difference between click and tone suppressions, which is consistent with low-level click and tone responses being amplified in the same way. The data are also consistent with the operating point of the OHC MET function varying smoothly from symmetric in the base to offset in the apex, and, in contrast, with the IHC MET function being offset throughout the cochlea. As previously reported, bias-tones presented alone excited AN fibers at one or more phases, a phenomena termed "peak splitting" with most BT excitation phases ~¼ cycle before or after the major suppression phase. We explain peak splitting as being due to distortion in multiple fluid drives to inner-hair-cell stereocilia.

Otology & Neurotology, Mar 1, 2019

The cervical vestibular evoked myogenic potential (cVEMP) has been used to evaluate patients with... more The cervical vestibular evoked myogenic potential (cVEMP) has been used to evaluate patients with Meniere's Disease (MD). Studied cVEMP metrics include: amplitude, threshold, frequency tuning and interaural asymmetry ratio (IAR). However, few studies compared these metrics in the same set of MD patients, and methodological differences prevent such a comparison across studies. This study investigates the value of different cVEMP metrics in distinguishing one set of MD patients from age-matched controls. Patients: Thirty patients with definite unilateral MD and twenty-three age-matched controls were prospectively included. All underwent cVEMP testing at 500, 750, 1000 and 2000 Hz on each side. Ears were separated into three groups: affected MD, unaffected MD and control. Main outcome measures: Sound level functions were obtained at each frequency, and normalized peak-to-peak amplitude (VEMPn), VEMP inhibition depth (VEMPid), threshold, frequency-tuning ratio and IAR were calculated. For all metrics, the differentiation between MD and control ears was compared using ROC curves. Results: 500 Hz cVEMP threshold, VEMPn and VEMPid were similarly good at distinguishing affected MD ears from healthy ears, with ROC area under the curves (AUCs) of >0.828 and optimal sensitivities and specificities of at least 80% and 70%. Combinations of these three metrics yielded slightly larger AUCs (>0.880). Tuning ratios and IAR were less effective in separating healthy from affected ears with AUCs ranging from 0.529-0.720.

Hearing Research, Nov 1, 2012

In the fifty years since Békésy was awarded the Nobel Prize, cochlear physiology has blossomed. M... more In the fifty years since Békésy was awarded the Nobel Prize, cochlear physiology has blossomed. Many topics that are now current are things Békésy could not have imagined. In this review we start by describing progress in understanding the origin of cochlear gross potentials, particularly the cochlear microphonic, an area in which Békésy had extensive experience. We then review progress in areas of cochlear physiology that were mostly unknown to Békésy, including: (1) stereocilia mechano-electrical transduction, force production, and response amplification, (2) outer hair cell (OHC) somatic motility and its molecular basis in prestin, (3) cochlear amplification and related micromechanics, including the evidence that prestin is the main motor for cochlear amplification, (4) the influence of the tectorial membrane, (5) cochlear micromechanics and the mechanical drives to inner hair cell stereocilia, (6) otoacoustic emissions, and (7) olivocochlear efferents and their influence on cochlear physiology. We then return to a subject that Békésy knew well: cochlear fluids and standing currents, as well as our present understanding of energy dependence on the lateral wall of the cochlea. Finally, we touch on cochlear pathologies including noise damage and aging, with an emphasis on where the field might go in the future.

Hearing Research, Oct 1, 2012

Recent studies indicate that the gap over outer hair cells (OHCs) between the reticular lamina (R... more Recent studies indicate that the gap over outer hair cells (OHCs) between the reticular lamina (RL) and the tectorial membrane (TM) varies cyclically during low-frequency sounds. Variation in the RL-TM gap produces radial fluid flow in the gap that can drive inner hair cell (IHC) stereocilia. Analysis of RL-TM gap changes reveals three IHC drives in addition to classic SHEAR. For upward basilar-membrane (BM) motion, IHC stereocilia are deflected in the excitatory direction by SHEAR and OHC-MOTILITY, but in the inhibitory direction by TM-PUSH and CILIA-SLANT. Upward BM motion causes OHC somatic contraction which tilts the RL, compresses the RL-TM gap over IHCs and expands the RL-TM gap over OHCs, thereby producing an outward (away from the IHCs) radial fluid flow which is the OHC-MOTILITY drive. For upward BM motion, the force that moves the TM upward also compresses the RL-TM gap over OHCs causing inward radial flow past IHCs which is the TM-PUSH drive. Motions that produce large tilting of OHC stereocilia squeeze the supra-OHC RL-TM gap and caused inward radial flow past IHCs which is the CILIA-SLANT drive. Combinations of these drives explain: (1) the reversal at high sound levels of auditory nerve (AN) initial peak (ANIP) responses to clicks, and medial olivocochlear (MOC) inhibition of ANIP responses below, but not above, the ANIP reversal, (2) dips and phase reversals in AN responses to tones in cats and chinchillas, (3) hypersensitivity and phase reversals in tuning-curve tails after OHC ablation, and (4) MOC inhibition of tail-frequency AN responses. The OHC-MOTILITY drive provides another mechanism, in addition to BM motion amplification, that uses active processes to enhance the output of the cochlea. The ability of these IHC drives to explain previously anomalous data provides strong, although indirect, evidence that these drives are significant and presents a new view of how the cochlea works at frequencies below 3 kHz.

Proceedings of the National Academy of Sciences of the United States of America, Feb 26, 2002

We develop an objective, noninvasive method for determining the frequency selectivity of cochlear... more We develop an objective, noninvasive method for determining the frequency selectivity of cochlear tuning at low and moderate sound levels. Applicable in humans at frequencies of 1 kHz and above, the method is based on the measurement of stimulus-frequency otoacoustic emissions and, unlike previous noninvasive physiological methods, does not depend on the frequency selectivity of masking or suppression. The otoacoustic measurements indicate that at low sound levels human cochlear tuning is more than twice as sharp as implied by standard behavioral studies and has a different dependence on frequency. New behavioral measurements designed to minimize the influence of nonlinear effects such as suppression agree with the emission-based values. A comparison of cochlear tuning in cat, guinea pig, and human indicates that, contrary to common belief, tuning in the human cochlea is considerably sharper than that found in the other mammals. The sharper tuning may facilitate human speech communication.

Journal of the Acoustical Society of America, Feb 1, 2023

bioRxiv (Cold Spring Harbor Laboratory), Nov 2, 2022

Journal of the Acoustical Society of America, May 1, 2006

There are afferent fibers in the vestibular nerve of cats and guinea pigs that respond to sound a... more There are afferent fibers in the vestibular nerve of cats and guinea pigs that respond to sound at levels within the normal range of hearing. Most acoustically responsive fibers are in the inferior vestibular nerve and have irregular spontaneous activity, although not as irregular as cochlear afferents. Single-fiber labeling shows that acoustically responsive, irregularly discharging (ARID) fibers originate in the saccule. ARID fibers traced centrally arborized extensively in vestibular nuclei and ventromedial to the cochlear nucleus. ARID fibers had broad, V-shaped tuning curves with best frequencies between 500 and 1000 Hz, thresholds of 90 dB SPL or more, and shapes comparable with tuning-curve tails of cochlear afferents. ARID fibers synchronized to a preferred phase of the tone cycle at levels approximately 10 dB lower than their firing-rate threshold. ARID spike rates increased monotonically with sound level without saturating at 115 dB SPL. Acoustic clicks evoked spikes in ARID fibers with minimum latencies less than 1.0 ms. Contraction of the middle-ear muscles decreased responses to sound, consistent with the sound transmission path being through the middle ear. In summary, there is strong evidence that the mammalian saccule responds to sound and sends acoustic information to the central nervous system. [Work supported by NIDCD RO1DC00235.]

The Journal of Physiology, Aug 1, 1980

1. The decay times of e.p.c.s (with acetyleholinesterase inhibited by neostigmine) were measured ... more 1. The decay times of e.p.c.s (with acetyleholinesterase inhibited by neostigmine) were measured with a view to inferring the extent of acetylcholine (ACh) binding. 2. E.p.c.s from muscles blocked by ACh decayed at less than half the rate of e.p.c.s from muscles blocked by tubocurarine, and slightly more slowly than m.e.p.c.s from unblocked muscles. 3. ACh prolonged e.p.c.s and reduced their amplitudes when added to muscles blocked by tubocurarine. 4. After treatment with ac-bungarotoxin, some e.p.c.s from muscles blocked by ACh were prolonged relative to e.p.c.s from muscles blocked by tubocurarine. 5. These phenomena are interpreted as indicating that either (a) desensitized receptors bind ACh and prolong e.p.c.s by buffered diffusion or (b) in highly desensitized muscles there is a population of active receptors which bind ACh for many milliseconds.

Frontiers in Systems Neuroscience, Sep 13, 2018

Otoacoustic emissions (OAEs) are often measured to non-invasively determine activation of medial ... more Otoacoustic emissions (OAEs) are often measured to non-invasively determine activation of medial olivocochlear (MOC) efferents in humans. Usually these experiments assume that ear-canal noise remains constant. However, changes in ear-canal noise have been reported in some behavioral experiments. We studied the variability of ear-canal noise in eight subjects who performed a two-interval-forced-choice (2IFC) sound-leveldiscrimination task on monaural tone pips in masker noise. Ear-canal noise was recorded directly from the unstimulated ear opposite the task ear. Recordings were also made with similar sounds presented, but no task done. In task trials, ear-canal noise was reduced at the time the subject did the discrimination, relative to the ear-canal noise level earlier in the trial. In two subjects, there was a decrease in ear-canal noise, primarily at 1-2 kHz, with a time course similar to that expected from inhibition by MOC activity elicited by the task-ear masker noise. These were the only subjects with spontaneous OAEs (SOAEs). We hypothesize that the SOAEs were inhibited by MOC activity elicited by the task-ear masker. Based on the standard rationale in OAE experiments that large bursts of ear-canal noise are artifacts due to subject movement, ear-canal noise bursts above a sound-level criterion were removed. As the criterion was lowered and more high-and moderate-level ear-canal noise bursts were removed, the reduction in ear-canal noise level at the time of the 2IFC discrimination decreased to almost zero, for the six subjects without SOAEs. This pattern is opposite that expected from MOC-induced inhibition (which is greater on lower-level sounds), but can be explained by the hypothesis that subjects move less and create fewer bursts of ear-canal noise when they concentrate on doing the task. In no-task trials for these six subjects, the ear-canal noise level was little changed throughout the trial. Our results show that measurements of MOC effects on OAEs must measure and account for changes in ear-canal noise,

Springer handbook of auditory research, 2008

Journal of the Acoustical Society of America, Aug 1, 2008

Conceptualizations of mammalian cochlear mechanics are based on basilar-membrane ͑BM͒ traveling w... more Conceptualizations of mammalian cochlear mechanics are based on basilar-membrane ͑BM͒ traveling waves that scale with frequency along the length of the cochlea, are amplified by outer hair cells ͑OHCs͒, and excite inner hair cells and auditory-nerve ͑AN͒ fibers in a simple way. However, recent experimental work has shown medial-olivocochlear ͑MOC͒ inhibition of AN responses to clicks that do not fit with this picture. To test whether this AN-initial-peak ͑ANIP͒ inhibition might result from hitherto unrecognized aspects of the traveling-wave or MOC-evoked inhibition, MOC effects on BM responses to clicks in the basal turns of guinea pig and chinchilla cochleae were measured. MOC stimulation inhibited BM click responses in a time and level dependent manner. Inhibition was not seen during the first half-cycle of the responses, but built up gradually, and ultimately increased the responses' decay rates. MOC stimulation also produced small phase leads in the response wave forms, but had little effect on the instantaneous frequency or the waxing and waning of the responses. These data, plus recent AN data, support the hypothesis that the MOC-evoked inhibitions of the traveling wave and of the ANIP response are separate phenomena, and indicate that the OHCs can affect at least two separate modes of excitation in the mammalian cochlea.

Ear and Hearing, 2013

Objectives-Presently available non-behavioral methods to estimate auditory thresholds perform les... more Objectives-Presently available non-behavioral methods to estimate auditory thresholds perform less well at frequencies below 1 kHz than at 1 kHz and above. For many uses, such as providing accurate infant hearing aid amplification for low-frequency vowels, we need an accurate non-behavioral method to estimate low-frequency thresholds. Here we develop a novel technique to estimate low-frequency cochlear thresholds based on the use of a previously-reported waveform. We determine how well the method works by comparing the resulting thresholds to thresholds from onset-response compound action potentials (CAPs) and single auditory-nerve (AN) fibers in cats. A long-term goal is to translate this technique for use in humans. Design-An electrode near the cochlea records a combination of cochlear microphonic (CM) and neural responses. In response to low-frequency, near threshold-level tones, the CM is almost sinusoidal while the neural responses occur preferentially at one phase of the tone. If the tone is presented again but with its polarity reversed, the neural response keeps the same shape, but shifts ½ cycle in time. Averaging responses to tones presented separately at opposite polarities overlaps and interleaves the neural responses and yields a waveform in which the CM is cancelled and the neural response appears twice each tone cycle, i.e. the resulting neural response is mostly at twice the tone frequency. We call the resultant waveform "the auditory nerve overlapped waveform" (ANOW). ANOW level functions were measured in anesthetized cats from 10 to 80 dB SPL in 10 dB steps using tones between 0.3 and 1 kHz. As a response metric, we calculated the magnitude of the ANOW component at twice the tone frequency (ANOW2f). The ANOW threshold was the sound level where the interpolated ANOW2f crossed a statistical criterion that was higher than 95% of the noise floor distribution. ANOW thresholds were compared to onset-CAP thresholds from the same recordings and single-AN-fiber thresholds from the same animals.

Journal of the Acoustical Society of America, 1996

The strength of the olivocochlear reflex has been assayed by comparing ipsilateral cochlear respo... more 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 ͑OAEs͒, whereas, in animal work, they have been assessed by measuring compound action potentials ͑CAPs͒. 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 ͑DP͒ 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.

The Journal of Physiology, Sep 22, 2006

Medial olivocochlear efferent (MOCE) neurones innervate the outer hair cells (OHCs) of the mammal... more 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.

Journal of the Acoustical Society of America, Jun 1, 1996

The onset behavior of the distortion product otoacoustic emission ͑DPOAE͒ at 2 f 1 Ϫ f 2 in anest... more The onset behavior of the distortion product otoacoustic emission ͑DPOAE͒ at 2 f 1 Ϫ f 2 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 ͑OCB͒ 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 2 f 1 Ϫ f 2 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.

Springer handbook of auditory research, 1996

Olivocochlear efferent neurons originate in the brain stem and terminate in the organ of Corti, t... more Olivocochlear efferent neurons originate in the brain stem and terminate in the organ of Corti, thereby allowing the central nervous system to influence the operation of the cochlea. This chapter reviews the physiology and possible functional utility of mammalian cochlear efferents. Efferent physiology in a few other hair cell systems is also reviewed for the insight provided into mammalian efferent

Brain Research, Sep 1, 1979