An Exploratory Study of Bimodal Electro-Aural Stimulation Through the Ear Canals for Tinnitus.

OBJECTIVE: The aim of this study was to explore the potential for bimodal auditory and noninvasive electrical stimulation at the ears to alleviate tonal, somatic tinnitus that was investigated in a small preliminary trial (11 participants). DESIGN: Auditory stimulation took the form of short "notched noise" bursts customized to each participant's tinnitus percept. Simultaneous pulsed electrical stimulation, intended to facilitate neuroplasticity, was delivered via hydrogel electrodes placed in opposite ears. RESULTS: After a 6-week intervention period, average Tinnitus Functional Index (TFI) and Tinnitus Primary Function Questionnaire (TPFQ) scores were consistent with clinically meaningful improvements in the study population. Magnitudes and effect sizes of improvements in TFI and TPFQ are comparable to those reported in other recent bimodal therapy studies using different auditory and electrical stimulation parameters. CONCLUSIONS: Our results should be considered preliminary given the small sample size, lack of crossover data, and small subject pool. When considered alongside other recent bimodal therapy results, we do believe that there are therapeutic benefits of bimodal stimulation for tinnitus sufferers that have the potential to help some with tinnitus, with a variety of stimulation parameters and electrode placements. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25444546.

Noise-induced cochlear neuropathy is selective for fibers with low spontaneous rates.

Acoustic overexposure can cause a permanent loss of auditory nerve fibers without destroying cochlear sensory cells, despite complete recovery of cochlear thresholds (Kujawa and Liberman 2009), as measured by gross neural potentials such as the auditory brainstem response (ABR). To address this nominal paradox, we recorded responses from single auditory nerve fibers in guinea pigs exposed to this type of neuropathic noise (4- to 8-kHz octave band at 106 dB SPL for 2 h). Two weeks postexposure, ABR thresholds had recovered to normal, while suprathreshold ABR amplitudes were reduced. Both thresholds and amplitudes of distortion-product otoacoustic emissions fully recovered, suggesting recovery of hair cell function. Loss of up to 30% of auditory-nerve synapses on inner hair cells was confirmed by confocal analysis of the cochlear sensory epithelium immunostained for pre- and postsynaptic markers. In single fiber recordings, at 2 wk postexposure, frequency tuning, dynamic range, postonset adaptation, first-spike latency and its variance, and other basic properties of auditory nerve response were all completely normal in the remaining fibers. The only physiological abnormality was a change in population statistics suggesting a selective loss of fibers with low- and medium-spontaneous rates. Selective loss of these high-threshold fibers would explain how ABR thresholds can recover despite such significant noise-induced neuropathy. A selective loss of high-threshold fibers may contribute to the problems of hearing in noisy environments that characterize the aging auditory system.

Primary neural degeneration in the Guinea pig cochlea after reversible noise-induced threshold shift.

Recent work in mouse showed that acoustic overexposure can produce a rapid and irreversible loss of cochlear nerve peripheral terminals on inner hair cells (IHCs) and a slow degeneration of spiral ganglion cells, despite full recovery of cochlear thresholds and no loss of inner or outer hair cells (Kujawa and Liberman, J Neurosci 29:14077-14085, 2009). This contrasts with earlier ultrastructural work in guinea pig suggesting that acute noise-induced neural degeneration is followed by full regeneration of cochlear nerve terminals in the IHC area (Puel et al., Neuroreport 9:2109-2114, 1998; Pujol and Puel, Ann N Y Acad Sci 884:249-254, 1999). Here, we show that the same patterns of primary neural degeneration reported for mouse are also seen in the noise-exposed guinea pig, when IHC synapses and cochlear nerve terminals are counted 1 week post-exposure in confocal images from immunostained whole mounts and that the same slow degeneration of spiral ganglion cells occurs despite no loss of IHCs and apparent recovery of cochlear thresholds. The data cast doubt on prior claims that there is significant neural regeneration and synaptogenesis in the adult cochlea and suggest that denervation of the inner hair cell is an important sequela of "reversible" noise-induced hearing loss, which likely applies to the human ear as well.

Adaptation reduces spike-count reliability, but not spike-timing precision, of auditory nerve responses.

Sensory systems use adaptive coding mechanisms to filter redundant information from the environment to efficiently represent the external world. One such mechanism found in most sensory neurons is rate adaptation, defined as a reduction in firing rate in response to a constant stimulus. In auditory nerve, this form of adaptation is likely mediated by exhaustion of release-ready synaptic vesicles in the cochlear hair cell. To better understand how specific synaptic mechanisms limit neural coding strategies, we examined the trial-to-trial variability of auditory nerve responses during short-term rate-adaptation by measuring spike-timing precision and spike-count reliability. After adaptation, precision remained unchanged, whereas for all but the lowest-frequency fibers, reliability decreased. Modeling statistical properties of the hair cell-afferent fiber synapse suggested that the ability of one or a few vesicles to elicit an action potential reduces the inherent response variability expected from quantal neurotransmitter release, and thereby confers the observed count reliability at sound onset. However, with adaptation, depletion of the readily releasable pool of vesicles diminishes quantal content and antagonizes the postsynaptic enhancement of reliability. These findings imply that during the course of short-term adaptation, coding strategies that employ a rate code are constrained by increased neural noise because of vesicle depletion, whereas those that employ a temporal code are not.

The effects of intense sound exposure on phase locking in the chick (Gallus domesticus) cochlear nerve.

Little is known about changes that occur to phase locking in the auditory nerve following exposure to intense and damaging levels of sound. The present study evaluated synchronization in the discharge patterns of cochlear nerve units collected from two groups of young chicks (Gallus domesticus), one shortly after removal from an exposure to a 120-dB, 900-Hz pure tone for 48 h and the other from a group of non-exposed control animals. Spontaneous activity, the characteristic frequency (CF), CF threshold and a phase-locked peri-stimulus time histogram were obtained for every unit in each group. Vector strength and temporal dispersion were calculated from these peri-stimulus time histograms, and plotted against the unit's CF. All parameters of unit responses were then compared between control and exposed units. The results in exposed units revealed that CF thresholds were elevated by 30-35 dB whereas spontaneous activity declined by 24%. In both control and exposed units a high degree of synchronization was observed in the low frequencies. The level of synchronization above approximately 0.5 kHz then systematically declined. The vector strengths in units recorded shortly after removal from the exposure were identical to those seen in control chicks. The deterioration in discharge activity of exposed units, seen in CF threshold and spontaneous activity, contrasted with the total absence of any overstimulation effect on synchronization. This suggested that synchronization arises from mechanisms unscathed by the acoustic trauma induced by the exposure.

Evidence that rapid vesicle replenishment of the synaptic ribbon mediates recovery from short-term adaptation at the hair cell afferent synapse.

We have employed both in vitro patch clamp recordings of hair cell synaptic vesicle fusion and in vivo single unit recording of cochlear nerve activity to study, at the same synapse, the time course, control, and physiological significance of readily releasable pool dynamics. Exocytosis of the readily releasable pool was fast, saturating in less than 50 ms, and recovery was also rapid, regaining 95% of its initial amplitude following a 200-ms period of repolarization. Longer depolarizations (greater than 250 ms) yielded a second, slower kinetic component of exocytosis. Both the second component of exocytosis and recovery of the readily releasable pool were blocked by the slow calcium buffer, EGTA. Sound-evoked afferent synaptic activity adapted and recovered with similar time courses as readily releasable pool exhaustion and recovery. Comparison of readily releasable pool amplitude, capture distances of calcium buffers, and number of vesicles tethered to the synaptic ribbon suggested that readily releasable pool dynamics reflect the depletion of release-ready vesicles tethered to the synaptic ribbon and the reloading of the ribbon with vesicles from the cytoplasm. Thus, we submit that rapid recovery of the cochlear hair cell afferent fiber synapse from short-term adaptation depends on the timely replenishment of the synaptic ribbon with vesicles from a cytoplasmic pool. This apparent rapid reloading of the synaptic ribbon with vesicles underscores important functional differences between synaptic ribbons in the auditory and visual systems.