Noise-induced hearing loss alters potassium-chloride cotransporter KCC2 and GABA inhibition in the auditory centers.

Homeostatic plasticity, the ability of neurons to maintain their averaged activity constant around a set point value, is thought to account for the central hyperactivity after hearing loss. Here, we investigated the putative role of GABAergic neurotransmission in this mechanism after a noise-induced hearing loss larger than 50 dB in high frequencies in guinea pigs. The effect of GABAergic inhibition is linked to the normal functioning of K + -Cl- co-transporter isoform 2 (KCC2) which maintains a low intracellular concentration of chloride. The expression of membrane KCC2 were investigated before and after noise trauma in the ventral and dorsal cochlear nucleus (VCN and DCN, respectively) and in the inferior colliculus (IC). Moreover, the effect of gabazine (GBZ), a GABA antagonist, was also studied on the neural activity in IC. We show that KCC2 is downregulated in VCN, DCN and IC 3 days after noise trauma, and in DCN and IC 30 days after the trauma. As expected, GBZ application in the IC of control animals resulted in an increase of spontaneous and stimulus-evoked activity. In the noise exposed animals, on the other hand, GBZ application decreased the stimulus-evoked activity in IC neurons. The functional implications of these central changes are discussed.

Changes in the spatiotemporal pattern of spontaneous activity across a cortical column after noise trauma.

In the auditory modality, noise trauma has often been used to investigate cortical plasticity as it causes cochlear hearing loss. One limitation of these past studies, however, is that the effects of noise trauma have been mostly documented at the granular layer, which is the main cortical recipient of thalamic inputs. Importantly, the cortex is composed of six different layers each having its own pattern of connectivity and specific role in sensory processing. The present study aims at investigating the effects of acute and chronic noise trauma on the laminar pattern of spontaneous activity (SA) in primary auditory cortex (A1) of the anesthetized guinea pig. We show that spontaneous activity is dramatically altered across cortical layers after acute and chronic noise-induced hearing loss. First, spontaneous activity was globally enhanced across cortical layers, both in terms of firing rate and amplitude of spike-triggered average of local field potentials. Second, current source density on (spontaneous) spike-triggered average of local field potentials indicates that current sinks develop in the supra- and infragranular layers. These latter results suggest that supragranular layers become a major input recipient and the propagation of spontaneous activity over a cortical column is greatly enhanced after acute and chronic noise-induced hearing loss. We discuss the possible mechanisms and functional implications of these changes.NEW & NOTEWORTHY The present study investigates the effects of acute and chronic noise trauma on the laminar pattern of spontaneous activity in the primary auditory cortex. Our study is first to report that noise trauma alters the sequence of cortical column activation during ongoing activity. In particular, we show that the supragranular layer becomes a major input recipient and the synaptic activity in the infragranular layers is enhanced.

Suppression of putative tinnitus-related activity by extra-cochlear electrical stimulation.

Studies on animals have shown that noise-induced hearing loss is followed by an increase of spontaneous firing at several stages of the central auditory system. This central hyperactivity has been suggested to underpin the perception of tinnitus. It was shown that decreasing cochlear activity can abolish the noise-induced central hyperactivity. This latter result further suggests that an approach consisting of reducing cochlear activity may provide a therapeutic avenue for tinnitus. In this context, extra-cochlear electric stimulation (ECES) may be a good candidate to modulate cochlear activity and suppress tinnitus. Indeed, it has been shown that a positive current applied at the round window reduces cochlear nerve activity and can suppress tinnitus reliably in tinnitus subjects. The present study investigates whether ECES with a positive current can abolish the noise-induced central hyperactivity, i.e., the putative tinnitus-related activity. Spontaneous and stimulus-evoked neural activity before, during and after ECES was assessed from single-unit recordings in the inferior colliculus of anesthetized guinea pigs. We found that ECES with positive current significantly decreases the spontaneous firing rate of neurons with high characteristic frequencies, whereas negative current produces the opposite effect. The effects of the ECES are absent or even reversed for neurons with low characteristic frequencies. Importantly, ECES with positive current had only a marginal effect on thresholds and tone-induced activity of collicular neurons, suggesting that the main action of positive current is to modulate the spontaneous firing. Overall, cochlear electrical stimulation may be a viable approach for suppressing some forms of (peripheral-dependent) tinnitus.

Temporary off-frequency listening after noise trauma.

Hearing loss is routinely estimated from the audiogram, even though this measure gives only a rough approximation of hearing. Indeed, cochlear regions functioning poorly, if at all, called dead regions, are not detected by a simple audiogram. To detect cochlear dead regions, additional measurements of psychophysical tuning curves or thresholds in background noise (TEN test) are required. A first aim of this study was to assess the presence of dead regions after impulse noise trauma using psychophysical tuning curves. The procedure we used was based on a compromise between the need to collect reliable estimates of psychophysical tuning curves and the limited time available to obtain these estimates in a hospital setting. Psychophysical tuning curves were measured using simultaneous masking with a 2-alternative forced choice paradigm, where the target was randomly placed in one of the two masker presentations. It is well known that some components of noise-induced hearing loss are reversible. A second aim of this study was to examine the potential recovery of dead regions after acoustic trauma. A third issue addressed in this article was the relationship between noise-induced dead regions and tinnitus. We found that 70% of the subjects had dead regions after noise trauma, while 88% reported tinnitus. Moreover, we found that the extent of dead regions probably diminished in about 50% of subjects, which highlights the ability of the human auditory system to recover from noise-induced hearing loss.

Neural changes in the auditory cortex of awake guinea pigs after two tinnitus inducers: salicylate and acoustic trauma.

Tinnitus, also called phantom auditory perception, is a major health problem in western countries. As such, a significant amount of effort has been devoted to understanding its mechanisms, including studies in animals wherein a supposed "tinnitus state" can be induced. Here, we studied on the same awake animals the effects of a high-dose of salicylate and of an acoustic trauma both at levels known to induce tinnitus. Recordings of cortical activity (local field potentials) from chronically implanted electrodes in the same animals under each condition allowed direct comparison of the effects of salicylate and trauma (noise trauma was carried out several days after full recovery from salicylate administration). Salicylate induced a systematic and reversible increase in amplitude of cortical responses evoked by tone bursts over a wide range of frequencies and intensities. The effects of noise trauma, though much more variable than those of salicylate, resulted in both increases and decreases in the amplitude of cortical responses. These alterations of cortical response amplitudes likely reflect associated hypoacusis and hyperacusis. The effects of salicylate administration and noise trauma on spontaneous activity were also studied. Fourier analysis did not reveal any increase in power within any given frequency band; rather, both treatments induced a decrease of power spectrum over a relatively broad frequency band (approximately 10-30 Hz). Entropy rate of spontaneous activity, a measure of complexity (temporal correlations), was found to decrease after salicylate but not after acoustic trauma. The present data on evoked potentials confirm salicylate effects at the cortical level and partially extend such effects to acoustic trauma. While the present study showed that both salicylate and noise trauma induced some changes of spontaneous activity in auditory cortex, none of these changes are interpretable in terms of potential neural correlate of tinnitus.

Effects of hearing aid fitting on the perceptual characteristics of tinnitus.

Restoration of auditory input through the use of hearing aids has been proposed as a potentially important means of altering tinnitus among those tinnitus sufferers who experience significant sensorineural hearing loss. In animal models of neural plasticity induced by noise trauma, high-frequency stimulation in deafferented regions of the auditory spectrum has been shown to modulate cortical reorganization after hearing loss, a result which suggests that the neural basis of tinnitus is subject to interference by acoustic stimulation. This study drew on deafferentation models to investigate the effect of hearing aids on the psychoacoustic properties of the tinnitus sensation, using both conventional amplification and high-bandwidth amplification regimes. The tinnitus percept was affected only weakly in the conventional amplification group, and was not at all affected in the high-bandwidth group. The changes observed under conventional, low-to-medium frequency amplification may indicate that the perceptual characteristics of tinnitus depend on the pattern of sensory inputs - notably a contrast in activity between adjacent central auditory regions of more and less afferent activity - while the absence of modifications in the high-bandwidth amplification group suggests limit on the tractability of the tinnitus percept. This limit to the malleability of the tinnitus percept may arise from either the extent of hearing deficits or the duration and robustness of the neuroplastic changes that originally give rise to tinnitus.

Neural correlates of an auditory afterimage in primary auditory cortex.

The Zwicker tone (ZT) is defined as an auditory negative afterimage, perceived after the presentation of an appropriate inducer. Typically, a notched noise (NN) with a notch width of 1/2 octave induces a ZT with a pitch falling in the frequency range of the notch. The aim of the present study was to find potential neural correlates of the ZT in the primary auditory cortex of ketamine-anesthetized cats. Responses of multiunits were recorded simultaneously with two 8-electrode arrays during 1 s and over 2 s after the presentation of a white noise (WN) and three NNs differing by the width of the notch, namely, 1/3 octave (NN1), 1/2 octave (NN2), and 2/3 octave (NN3). Both firing rate (FR) and peak cross-correlation coefficient (p) were evaluated for time windows of 500 ms. The cortical units were grouped according to whether their characteristic frequency (CF) was inside ("In" neurons) or outside ("Out" neurons) a 1-octave-wide frequency band centered on the notch center frequency. The ratios between the FRs and the rhos for each NN and the WN condition and for each group of neurons were then statistically evaluated. The ratios of FRs were significantly increased during and after the presentation of the NN for the "In" neurons. In contrast, the changes for the t" neurons were small and most often insignificant. The ratios of the p values differed significantly from 1 in the "In-In" and "In-Out" groups during stimulation as well as after it. We also found that the ps of "Out" neurons were dependent on the type of NN. Potentially, a combination of increased p and increased FR might be a neurophysiological correlate of the ZT.

Changes in spontaneous neural activity immediately after an acoustic trauma: implications for neural correlates of tinnitus.

Changes in spontaneous activity, recorded over 15-min periods before, immediately after and within hours after an acute acoustic trauma, were studied in primary auditory cortex of ketamine-anesthetized cats. We focused on the spontaneous firing rate (SFR), the peak cross-correlation coefficient (rho) and burst-firing activity. Multi-units (MUs) were grouped according to characteristic frequency (CF): MUs with a CF below the trauma-tone frequency (TF) were labeled as Be, those with a CF within 1 octave above the TF were labeled as Ab1 and those with a CF more than 1 octave above the TF were labeled as Ab2. Immediately after the trauma, the SFR was not significantly changed. The percentage of time that neurons were bursting, the mean burst duration, the number of spikes per burst and the mean inter-spike interval in a burst were enhanced. rho was locally increased in the Ab1-Ab2 and Ab2-Ab2 groups. A few hours post trauma, the SFR was increased in the Be and Ab2 groups, whereas burst-firing returned to pre-exposure levels. Moreover, rho was elevated in the Be-Ab2, Ab1-Ab2 and Ab2-Ab2 groups; this increase was significantly correlated to the changes in SFR. The results are discussed in the context of a neural correlate of tinnitus.