Publications using TDT

The kinase Akt is a key downstream mediator of the phosphoinositide-3-kinase signaling pathway and participates in a variety of cellular processes. Akt comprises three isoforms each encoded by a separate gene. There is evidence to indicate that Akt is involved in the survival and protection of auditory hair cells in vitro. However, little is known about the physiological role of Akt in the inner ear-especially in the intact animal. To elucidate this issue, we first analyzed the mRNA expression of the three Akt isoforms in the inner ear of C57/BL6 mice by real-time PCR. Next, we tested the susceptibility to gentamicin-induced auditory hair cell loss in isoform-specific Akt knockout mice compared to wild-types (C57/BL6) in vitro. To analyze the effect of gene deletion in vivo, hearing and cochlear microanatomy were evaluated in Akt isoform knockout animals. In this study, we found that all three Akt isoforms are expressed in the cochlea. Our results further indicate that Akt2 and Akt3 enhance hair cell resistance to ototoxicity, while Akt1 does not. Finally, we determined that untreated Akt1 and Akt2/Akt3 double knockout mice display significant hearing loss, indicating a role for these isoforms in normal hearing. Taken together, our results indicate that each of the Akt isoforms plays a distinct role in the mammalian inner ear.

Acute seizures after a severe brain insult can often lead to epilepsy and cognitive impairment. Aberrant hippocampal neurogenesis follows the insult but the role of adult-generated neurons in the development of chronic seizures or associated cognitive deficits remains to be determined. Here we show that the ablation of adult neurogenesis before pilocarpine-induced acute seizures in mice leads to a reduction in chronic seizure frequency. We also show that ablation of neurogenesis normalizes epilepsy-associated cognitive deficits. Remarkably, the effect of ablating adult neurogenesis before acute seizures is long lasting as it suppresses chronic seizure frequency for nearly 1 year. These findings establish a key role of neurogenesis in chronic seizure development and associated memory impairment and suggest that targeting aberrant hippocampal neurogenesis may reduce recurrent seizures and restore cognitive function following a pro-epileptic brain insult.

Neuromodulation is an increasingly accepted treatment for neurological and psychiatric disorders but is limited by its invasiveness or its inability to target deep brain structures using noninvasive techniques. We propose a new concept called Multimodal Synchronization Therapy (mSync) for achieving targeted activation of the brain via noninvasive and precisely timed activation of auditory, visual, somatosensory, motor, cognitive and limbic pathways. In this initial study in guinea pigs, we investigated mSync using combined activation of just the auditory and somatosensory pathways, which induced differential and timing dependent plasticity in neural firing within deep brain and cortical regions of the auditory system. Furthermore, by varying the location of somatosensory stimulation across the body, we increased or decreased spiking activity across different neurons. These encouraging results demonstrate the feasibility of systematically modulating the brain using mSync. Considering that hearing disorders such as tinnitus and hyperacusis have been linked to abnormal and hyperactive firing patterns within the auditory system, these results open up the possibility for using mSync to decrease this pathological activity by varying stimulation parameters. Incorporating multiple types of pathways beyond just auditory and somatosensory inputs and using other activation patterns may enable treatment of various brain disorders.

The dorsal and ventral hippocampal regions (dHP and vHP) are proposed to have distinct functions. Electrophysiological studies have revealed intra-hippocampal variances along the dorsoventral axis. Nevertheless, the extra-hippocampal influences of dHP and vHP activities remain unclear. In this study, we compared the spatial distribution of brain-wide responses upon dHP or vHP activation and further estimate connection strengths between the dHP and the vHP with corresponding extra-hippocampal areas. To achieve this, we first investigated responses of local field potential (LFP) and multi unit activities (MUA) upon light stimulation in the hippocampus of an anesthetized transgenic mouse, whose CA1 pyramidal neurons expressed a step-function opsin variant of channelrhodopsin-2 (ChR2). Optogenetic stimulation increased hippocampal LFP power at theta, gamma, and ultra-fast frequency bands, and augmented MUA, indicating light-induced activation of CA1 pyramidal neurons. Brain-wide responses examined using fMRI revealed that optogenetic activation at the dHP or vHP caused blood oxygenation level-dependent (BOLD) fMRI signals in situ. Although activation at the dHP induced BOLD responses at the vHP, the opposite was not observed. Outside the hippocampal formation, activation at the dHP, but not the vHP, evoked BOLD responses at the retrosplenial cortex (RSP), which is in line with anatomical evidence. In contrast, BOLD responses at the lateral septum (LS) were induced only upon vHP activation, even though both dHP and vHP send axonal fibers to the LS. Our findings suggest that the primary targets of dHP and vHP activation are distinct, which concurs with attributed functions of the dHP and RSP in spatial memory, as well as of the vHP and LS in emotional responses.

Excessive exposure to noise damages the principal cochlear structures leading to hearing impairment. Inflammatory and immune responses are central mechanisms in cochlear defensive response to noise but, if unregulated, they contribute to inner ear damage and hearing loss. Transforming growth factor β (TGF-β) is a key regulator of both responses and high levels of this factor have been associated with cochlear injury in hearing loss animal models. To evaluate the potential of targeting TGF-β as a therapeutic strategy for preventing or ameliorating noise-induced hearing loss (NIHL), we studied the auditory function, cochlear morphology, gene expression and oxidative stress markers in mice exposed to noise and treated with TGF-β1 peptidic inhibitors P17 and P144, just before or immediately after noise insult. Our results indicate that systemic administration of both peptides significantly improved both the evolution of hearing thresholds and the degenerative changes induced by noise-exposure in lateral wall structures. Moreover, treatments ameliorated the inflammatory state and redox balance. These therapeutic effects were dose-dependent and more effective if the TGF-β1 inhibitors were administered prior to inducing the injury. In conclusion, inhibition of TGF-β1 actions with antagonistic peptides represents a new, promising therapeutic strategy for the prevention and repair of noise-induced cochlear damage.

The interplay of cortical excitation and inhibition is a fundamental feature of cortical information processing. Excitation and inhibition in single cortical neurons are balanced in their response to optimal sensory stimulation due to thalamocortical feedforward microcircuitry. It is unclear whether the balance between cortical excitation and inhibition is maintained at the threshold stimulus level. Using in vivo whole-cell patch-clamp recording of thalamocortical recipient neurons in the primary auditory cortex of mice, we examined the tone-evoked excitatory and inhibitory postsynaptic currents at threshold levels. Similar to previous reports, tone induced excitatory postsynaptic currents when the membrane potentials were held at 70 mV and inhibitory postsynaptic currents when the membrane potentials were held at 0 mV on single cortical neurons. This coupled excitation and inhibition is not demonstrated when threshold-level tone stimuli are presented. In most cases, tone induced only excitatory postsynaptic current. The best frequencies of excitatory and inhibitory responses were often different and thresholds of inhibitory responses were mostly higher than those of excitatory responses. Our data suggest that the excitatory and inhibitory inputs to single cortical neurons are imbalanced at the threshold level. This imbalance may result from the inherent dynamics of thalamocortical feedforward microcircuitry.

Tinnitus has been suggested to arise from neuronal hyperactivity in auditory areas of the brain, and anti-epileptic drugs are sometimes used to provide relief from tinnitus. Recently, the anti-epileptic properties of the cannabinoid drugs have gained increasing interest; however, the use of cannabinoids as a form of treatment for tinnitus is controversial. In this study, we tested whether a combination of delta-9-tetrahydrocannabinol (delta-9-THC) and cannabidiol (CBD), delivered in a 1:1 ratio, could affect tinnitus perception in a rat model of acoustic trauma-induced tinnitus. Following sham treatment or acoustic trauma, the animals were divided into the following groups: (1) sham (i.e., no acoustic trauma) with vehicle treatment; (2) sham with drug treatment (i.e., delta-9-THC + CBD); (3) acoustic trauma-exposed exhibiting tinnitus, with drug treatment; and (4) acoustic trauma-exposed exhibiting no tinnitus, with drug treatment. The animals received either the vehicle or the cannabinoid drugs every day, 30 min before the tinnitus behavioral testing. Acoustic trauma caused a significant increase in the auditory brainstem response (ABR) thresholds in the exposed animals, indicating hearing loss; however, there was a partial recovery over 6 months. Acoustic trauma did not always result in tinnitus; however, among those that did exhibit tinnitus, some of them had tinnitus at multiple frequencies while others had it only at a single frequency. The cannabinoids significantly increased the number of tinnitus animals in the exposed-tinnitus group, but not in the sham group. The results suggest that cannabinoids may promote the development of tinnitus, especially when there is pre-existing hearing damage.

This work assesses the efficiency of the Codacs system actuator (Cochlear Ltd., Sydney Australia) in different inner ear stimulation modalities. Originally the actuator was intended for direct perilymph stimulation after stapedotomy using a piston prosthesis. A possible alternative application is the stimulation of middle ear structures or the round window (RW). Here the perilymph stimulation with a K-piston through a stapes footplate (SFP) fenestration (N = 10) as well as stimulation of the stapes head (SH) with a Bell prosthesis (N = 9), SFP stimulation with an Omega/Aerial prosthesis (N = 8) and reverse RW stimulation (N = 10) were performed in cadaveric human temporal bones (TBs). Codacs actuator output is expressed as equivalent sound pressure level (eq. SPL) using RW and SFP displacement responses, measured by Laser Doppler velocimetry as reference. The axial actuator coupling force in stimulation of stapes and RW was adjusted to ~5 mN. The Bell prosthesis and Omega/Aerial prosthesis stimulation generated similar mean eq. SPLs (Bell: 127.5-141.8 eq. dB SPL; Omega/Aerial: 123.6-143.9 eq. dB SPL), being significantly more efficient than K-piston perilymph stimulation (108.6-131.6 eq. dB SPL) and RW stimulation (108.3-128.2 eq. dB SPL). Our results demonstrate that SH, SFP and RW are adequate alternative stimulation sites for the Codacs actuator using coupling prostheses and an axial coupling force of ~5 mN. Based on the eq. SPLs, all investigated methods were adequate for in vivo hearing aid applications, provided that experimental conditions including constant coupling force will be implemented.

Studies that use prolonged periods of sensory stimulation report associations between regional reductions in neural activity and negative blood oxygenation level-dependent (BOLD) signaling. However, the neural generators of the negative BOLD response remain to be characterized. Here, we use single-impulse electrical stimulation of the whisker pad in the anesthetized rat to identify components of the neural response that are related to “negative” hemodynamic changes in the brain. Laminar multiunit activity and local field potential recordings of neural activity were performed concurrently with two-dimensional optical imaging spectroscopy measuring hemodynamic changes. Repeated measurements over multiple stimulation trials revealed significant variations in neural responses across session and animal datasets. Within this variation, we found robust long-latency decreases (300 and 2000 ms after stimulus presentation) in gamma-band power (30–80 Hz) in the middle-superficial cortical layers in regions surrounding the activated whisker barrel cortex. This reduction in gamma frequency activity was associated with corresponding decreases in the hemodynamic responses that drive the negative BOLD signal. These findings suggest a close relationship between BOLD responses and neural events that operate over time scales that outlast the initiating sensory stimulus, and provide important insights into the neurophysiological basis of negative neuroimaging signals.

Sensory information acquires meaning to adaptively guide behaviors. Despite odors mediating a number of vital behaviors, the components of the olfactory system responsible for assigning meaning to odors remain unclear. The olfactory tubercle (OT), a ventral striatum structure that receives monosynaptic input from the olfactory bulb, is uniquely positioned to transform odor information into behaviorally relevant neural codes. No information is available, however, on the coding of odors among OT neurons in behaving animals. In recordings from mice engaged in an odor discrimination task, we report that the firing rate of OT neurons robustly and flexibly encodes the valence of conditioned odors over identity, with rewarded odors evoking greater firing rates. This coding of rewarded odors occurs before behavioral decisions and represents subsequent behavioral responses. We predict that the OT is an essential region whereby odor valence is encoded in the mammalian brain to guide goal-directed behaviors.

Lifestyle including smoking, noise exposure with MP3 player and drinking alcohol are considered as risk factors for affecting hearing synergistically. However, little is known about the association of cigarette smoking with hearing impairment among subjects who carry a lifestyle without using MP3 player and drinking alcohol. We showed here the influence of smoking on hearing among Bangladeshi subjects who maintain a lifestyle devoid of using MP3 player and drinking alcohol. A total of 184 subjects (smokers: 90; non-smokers: 94) were included considering their duration and frequency of smoking for conducting this study. The mean hearing thresholds of non-smoker subjects at 1, 4, 8 and 12 kHz frequencies were 5.63 ± 2.10, 8.56±5.75, 21.06 ± 11.06, 40.79 ± 20.36 decibel (dB), respectively and that of the smokers were 7 ± 3.8, 13.27 ± 8.4, 30.66 ± 12.50 and 56.88 ± 21.58 dB, respectively. The hearing thresholds of the smokers at 4, 8 and 12 kHz frequencies were significantly (p<0.05) higher than those of the non-smokers, while no significant differences were observed at 1 kHz frequency. We also observed no significant difference in auditory thresholds among smoker subgroups based on smoking frequency. In contrast, subjects smoked for longer duration (>5 years) showed higher level of auditory threshold (62.16 ± 19.87 dB) at 12 kHz frequency compared with that (41.52 ± 19.21 dB) of the subjects smoked for 1-5 years and the difference in auditory thresholds was statistically significant (p<0.0002). In this study, the Brinkman Index (BI) of smokers was from 6 to 440 and the adjusted odds ratio showed a positive correlation between hearing loss and smoking when adjusted for age and body mass index (BMI). In addition, age, but not BMI, also played positive role on hearing impairment at all frequencies. Thus, these findings suggested that cigarette smoking affects hearing level at all the frequencies tested but most significantly at extra higher frequencies.

Background: Data on sex-specific differences in sound production, acoustic behaviour and hearing abilities in fishes are rare. Representatives of numerous catfish families are known to produce sounds in agonistic contexts (intraspecific aggression and interspecific disturbance situations) using their pectoral fins. The present study investigates differences in agonistic behaviour, sound production and hearing abilities in males and females of a callichthyid catfish. Methodology/principal findings: Eight males and nine females of the armoured catfish Megalechis thoracata were investigated. Agonistic behaviour displayed during male-male and female-female dyadic contests and sounds emitted were recorded, sound characteristics analysed and hearing thresholds measured using the auditory evoked potential (AEP) recording technique. Male pectoral spines were on average 1.7-fold longer than those of same-sized females. Visual and acoustic threat displays differed between sexes. Males produced low-frequency harmonic barks at longer distances and thumps at close distances, whereas females emitted broad-band pulsed crackles when close to each other. Female aggressive sounds were significantly shorter than those of males (167 ms versus 219 to 240 ms) and of higher dominant frequency (562 Hz versus 132 to 403 Hz). Sound duration and sound level were positively correlated with body and pectoral spine length, but dominant frequency was inversely correlated only to spine length. Both sexes showed a similar U-shaped hearing curve with lowest thresholds between 0.2 and 1 kHz and a drop in sensitivity above 1 kHz. The main energies of sounds were located at the most sensitive frequencies. Conclusions/significance: Current data demonstrate that both male and female M. thoracata produce aggressive sounds, but the behavioural contexts and sound characteristics differ between sexes. Sexes do not differ in hearing, but it remains to be clarified if this is a general pattern among fish. This is the first study to describe sex-specific differences in agonistic behaviour in fishes.

Responses of neurons to binaural, harmonic complex stimuli in urethane-anesthetized guinea pig inferior colliculus (IC) are reported. To assess the binaural integration of harmonicity cues for sound segregation and grouping, responses were measured to harmonic complexes with different fundamental frequencies presented to each ear. Simultaneously gated harmonic stimuli with fundamental frequencies of 125 Hz and 145 Hz were presented to the left and right ears, respectively, and recordings made from 96 neurons with characteristic frequencies >2 kHz in the central nucleus of the IC. Of these units, 70 responded continuously throughout the stimulus and were excited by the stimulus at the contralateral ear. The stimulus at the ipsilateral ear excited (EE: 14%; 10/70), inhibited (EI: 33%; 23/70), or had no significant effect (EO: 53%; 37/70), defined by the effect on firing rate. The neurons phase locked to the temporal envelope at each ear to varying degrees depending on signal level. Many of the cells (predominantly EO) were dominated by the response to the contralateral stimulus. Another group (predominantly EI) synchronized to the contralateral stimulus and were suppressed by the ipsilateral stimulus in a phasic manner. A third group synchronized to the stimuli at both ears (predominantly EE). Finally, a group only responded when the waveform peaks from each ear coincided. We conclude that these groups of neurons represent different “streams” of information but exhibit modifications of the response rather than encoding a feature of the stimulus, like pitch.

Cartilage conduction (CC) is a new form of sound transmission which is induced by a transducer being placed on the aural cartilage. Although the conventional forms of sound transmission to the cochlea are classified into air or bone conduction (AC or BC), previous study demonstrates that CC is not classified into AC or BC (Laryngoscope 124: 1214-1219). Next interesting issue is whether CC is a hybrid of AC and BC. Seven volunteers with normal hearing participated in this experiment. The threshold-shifts by water injection in the ear canal were measured. AC, BC, and CC thresholds at 0.5-4 kHz were measured in the 0%-, 40%-, and 80%-water injection conditions. In addition, CC thresholds were also measured for the 20%-, 60%-, 100%-, and overflowing-water injection conditions. The contributions of the vibrations of the cartilaginous portion were evaluated by the threshold-shifts. For AC and BC, the threshold-shifts by the water injection were 22.6-53.3 dB and within 14.9 dB at the frequency of 0.5-4 kHz, respectively. For CC, when the water was filled within the bony portion, the thresholds were elevated to the same degree as AC. When the water was additionally injected to reach the cartilaginous portion, the thresholds at 0.5 and 1 kHz dramatically decreased by 27.4 and 27.5 dB, respectively. In addition, despite blocking AC by the injected water, the CC thresholds in force level were remarkably lower than those for BC. The vibration of the cartilaginous portion contributes to the sound transmission, particularly in the low frequency range. Although the airborne sound is radiated into the ear canal in both BC and CC, the mechanism underlying its generation is different between them. CC generates airborne sound in the canal more efficiently than BC. The current findings suggest that CC is not a hybrid of AC and BC.

Interval-counting neurons (ICNs) respond after a threshold number of sound pulses have occurred with specific intervals; a single aberrant interval can reset the counting process. Female gray treefrogs, Hyla chrysoscelis and H. versicolor, discriminate against synthetic 'calls' possessing a single interpulse interval 2-3 three times the optimal value, suggesting that ICNs are important for call recognition. The calls of H. versicolor consist of pulses that are longer in duration, rise more slowly in amplitude and are repeated at a slower rate than those of H. chrysoscelis. Results of recordings from midbrain auditory neurons in these species include: (1) ICNs were found in both species and their temporal selectivity appeared to result from interplay between excitation and inhibition; (2) band-pass cells in H. versicolor were tuned to slower pulse rates than those in H. chrysoscelis; (3) ICNs that were selective for slow-rise pulse shape were found almost exclusively in H. versicolor, but fast-rise-selective neurons were found in both species, and (4) band-suppression ICNs in H. versicolor showed response minima at higher pulse rates than those in H. chrysoscelis. Selectivity of midbrain ICNs for pulse rise time and repetition rate thus correlate well with discriminatory abilities of these species that promote reproductive isolation.

A significant challenge in tinnitus research lies in explaining how acoustic insult leads to tinnitus in some individuals, but not others. One possibility is genetic variability in the expression and function of neuromodulators - components of neural signaling that alter the balance of excitation and inhibition in neural circuits. An example is nitric oxide (NO) - a free radical and potent neuromodulator in the mammalian brain - that regulates plasticity via both pre-synaptic and postsynaptic mechanisms. Changes in NO have previously been implicated in tinnitus generation, specifically in the ventral cochlear nucleus (VCN). Here, we examined nitric oxide synthase (NOS) - the enzyme responsible for NO production - in the guinea pig VCN following acoustic trauma. NOS was present in most cell types - including spherical and globular bushy cells, small, medium, and large multipolar cells, and octopus cells - spanning the entire extent of the VCN. The staining pattern was symmetrical in control animals. Unilateral acoustic over-exposure (AOE) resulted in marked asymmetries between ipsilateral and contralateral sides of the VCN in terms of the distribution of NOS across the cochlear nuclei in animals with behavioral evidence of tinnitus: fewer NOS-positive cells and a reduced level of NOS staining was present across the whole extent of the contralateral VCN, relative to the ipsilateral VCN. The asymmetric pattern of NOS-containing cells was observed as early as 1 day after AOE and was also present in some animals at 3, 7, and 21 days after AOE. However, it was not until 8 weeks after AOE, when tinnitus had developed, that asymmetries were significant overall, compared with control animals. Asymmetrical NOS expression was not correlated with shifts in the threshold hearing levels. Variability in NOS expression between animals may represent one underlying difference that can be linked to whether or not tinnitus develops after noise exposure.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) has largely replaced ablative therapies for Parkinson's disease. Because of the similar efficacies of the two treatments, it has been proposed that DBS acts by creating an “informational lesion,” whereby pathologic neuronal firing patterns are replaced by low-entropy, stimulus-entrained firing patterns. The informational lesion hypothesis, in its current form, states that DBS blocks the transmission of all information from the basal ganglia, including both pathologic firing patterns and normal, task-related modulations in activity. We tested this prediction in two healthy rhesus macaques by recording single-unit spiking activity from the globus pallidus (232 neurons) while the animals completed choice reaction time reaching movements with and without STN-DBS. Despite strong effects of DBS on the activity of most pallidal cells, reach-related modulations in firing rate were equally prevalent in the DBS-on and DBS-off states. This remained true even when the analysis was restricted to cells affected significantly by DBS. In addition, the overall form and timing of perimovement modulations in firing rate were preserved between DBS-on and DBS-off states in the majority of neurons (66%). Active movement and DBS had largely additive effects on the firing rate of most neurons, indicating an orthogonal relationship in which both inputs contribute independently to the overall firing rate of pallidal neurons. These findings suggest that STN-DBS does not act as an indiscriminate informational lesion but rather as a filter that permits task-related modulations in activity while, presumably, eliminating the pathological firing associated with parkinsonism.

The mouse vomeronasal organ (VNO) plays a critical role in semiochemical detection and social communication. Vomeronasal stimuli are typically secreted in various body fluids. Following direct contact with urine deposits or other secretions, a peristaltic vascular pump mediates fluid entry into the recipient's VNO. Therefore, while vomeronasal sensory neurons (VSNs) sample various stimulatory semiochemicals dissolved in the intraluminal mucus, they might also be affected by the general physicochemical properties of the “solvent.” Here, we report cycle stage-correlated variations in urinary pH among female mice. Estrus-specific pH decline is observed exclusively in urine samples from sexually experienced females. Moreover, patch-clamp recordings in acute VNO slices reveal that mouse VSNs reliably detect extracellular acidosis. Acid-evoked responses share the biophysical and pharmacological hallmarks of the hyperpolarization-activated current I h . Mechanistically, VSN acid sensitivity depends on a pH-induced shift in the voltage-dependence of I h activation that causes the opening of HCN channels at rest, thereby increasing VSN excitability. Together, our results identify extracellular acidification as a potent activator of vomeronasal I h and suggest HCN channel-dependent vomeronasal gain control of social chemosignaling. Our data thus reveal a potential mechanistic basis for stimulus pH detection in rodent chemosensory communication.

There are two types of sensory cells in the mammalian cochlea, inner hair cells, which make synaptic contact with auditory-nerve afferent fibers, and outer hair cells that are innervated by crossed and uncrossed medial olivocochlear (MOC) efferent fibers. Contralateral acoustic stimulation activates the uncrossed efferent MOC fibers reducing cochlear neural responses, thus modifying the input to the central auditory system. The chinchilla, among all studied mammals, displays the lowest percentage of uncrossed MOC fibers raising questions about the strength and frequency distribution of the contralateral-sound effect in this species. On the other hand, MOC effects on cochlear sensitivity have been mainly studied in anesthetized animals and since the MOC-neuron activity depends on the level of anesthesia, it is important to assess the influence of anesthesia in the strength of efferent effects. Seven adult chinchillas (Chinchilla laniger) were chronically implanted with round-window electrodes in both cochleae. We compared the effect of contralateral sound in awake and anesthetized condition. Compound action potentials (CAP) and cochlear microphonics (CM) were measured in the ipsilateral cochlea in response to tones in absence and presence of contralateral sound. Control measurements performed after middle-ear muscles section in one animal discarded any possible middle-ear reflex activation. Contralateral sound produced CAP amplitude reductions in all chinchillas, with suppression effects greater by about 1-3 dB in awake than in anesthetized animals. In contrast, CM amplitude increases of up to 1.9 dB were found in only three awake chinchillas. In both conditions the strongest efferent effects were produced by contralateral tones at frequencies equal or close to those of ipsilateral tones. Contralateral CAP suppressions for 1-6 kHz ipsilateral tones corresponded to a span of uncrossed MOC fiber innervation reaching at least the central third of the chinchilla cochlea.

Objectives: To determine whether suprathreshold measures of auditory function, such as distortion-product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABRs), are correlated with noise exposure history in normal-hearing human ears. Recent data from animal studies have revealed significant deafferentation of auditory nerve fibers after full recovery from temporary noise-induced hearing loss. Furthermore, these data report smaller ABR wave I amplitudes in noise-exposed animal ears when compared with non-noise-exposed control animals or prenoise exposure amplitudes in the same animal. It is unknown whether a similar phenomenon exists in the normal-hearing, noise-exposed human ear. Design: Thirty normal-hearing human subjects with a range of noise exposure backgrounds (NEBs) participated in this study. NEB was quantified by the use of a noise exposure questionnaire that extensively queried loud sound exposure during the previous 12 months. DPOAEs were collected at three f2s (1, 2, and 4 kHz) over a range of L2s. DPOAE stimulus level began at 80 dB forward-pressure level and decreased in 10 dB steps. Two-channel ABRs were collected in response to click stimuli and 4 kHz tone bursts; one channel used an ipsilateral mastoid electrode and the other an ipsilateral tympanic membrane electrode. ABR stimulus level began at 90 dB nHL and was decreased in 10 dB steps. Amplitudes of waves I and V of the ABR were analyzed. Results: A statistically significant relationship between ABR wave I amplitude and NEB was found for clicked-evoked ABRs recorded at a stimulus level of 90 dB nHL using a mastoid recording electrode. For this condition, ABR wave I amplitudes decreased as a function of NEB. Similar systematic trends were present for ABRs collected in response to clicks and 4 kHz tone bursts at additional suprathreshold stimulation levels (≥70 dB nHL). The relationship weakened and disappeared with decreases in stimulation level (≤60 dB nHL). Similar patterns were present for ABRs collected using a tympanic membrane electrode. However, these relationships were not statistically significant and were weaker and more variable than those collected using a mastoid electrode. In contrast to the findings for ABR wave I, wave V amplitude was not significantly related to NEB. Furthermore, there was no evidence of a systematic relationship between suprathreshold DPOAEs and NEB. Conclusions: A systematic trend of smaller ABR wave I amplitudes was found in normal-hearing human ears with greater amounts of voluntary NEB in response to suprathreshold clicks and 4 kHz tone bursts. These findings are consistent with the data from previous work completed in animals, where the reduction in suprathreshold responses was a result of deafferentation of high-threshold/low-spontaneous rate auditory nerve fibers. These data suggest that a similar mechanism might be operating in human ears after exposure to high sound levels. However, evidence of this damage is only apparent when examining suprathreshold wave I amplitude of the ABR. In contrast, suprathreshold DPOAE level was not significantly related to NEB. This was expected, given noise-induced auditory damage findings in animal ears did not extend to the outer hair cells, the generator for the DPOAE response.