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.

Influencia de la etnia y el sexo en la ingesta de alimentos como factores de riesgo de malnutrición en escolares / Influence of ethnicity and gender in school children food intake as malnutrition risk factors

La dieta de los niños en nuestro país suele ser deficitaria en frutas y verduras y rica en alimentos hipercalóricos. El objetivo del presente estudio es valorar la frecuencia de la ingesta de los grupos de alimentos en escolares de nuestro medio y la influencia sobre ella del sexo y la etnicidad. Se valoraron en una población de 383 niños de 2.º, 3.º y 4.º de Educación Primaria las características socioeconómicas y demográficas, los estilos de vida y la frecuencia de ingesta de grupos de alimentos. Los niños ingirieron más raciones diarias de alimentos ricos en hidratos de carbono (4,38 ± 1,6 frente a 3,97 ± 1,4; p=0,03) y más lácteos (3,23 ± 1,1 frente a 2,83 ± 1,0; p= 0,002) que las niñas; por otro lado, la niñas consumieron más golosinas que los niños (2,81 ± 3,9 frente a 2,01 ± 2,3 raciones por semana; p= 0,03). Un alto porcentaje de niños no cumplía con las recomendaciones habituales de ingesta por defecto de frutas y verduras (78,1%), lácteos (43,4%) e hidratos de carbono (42,8%), y por exceso de proteicos (8,1%), bollería (21,2%),golosinas (18,9%) y refrescos-snacks (8,7%). Los niños pertenecientes al grupo con etnicidad ingirieron significativamente menos lácteos, alimentos proteicos y fruta-verdura y, sin embargo, más bollería, golosinas y refrescos-snacks que los niños sin etnicidad. En el análisis de la relación entre los distintos grupos de alimentos se han encontrado dos asociaciones significativas (p <0,01): 1) la ingesta de frutas y verduras se asoció a un mayor consumo de hidratos de carbono y de pescado, y aun menor consumo de refrescos-snacks y tiempo frente al televisor; 2) la ingesta de bollería se asoció a un mayor consumo de refrescos/snacks y de golosinas. El estudio concluye que el sexo y la etnicidad son factores que influyen en la dieta de los niños en edad escolar y deben considerarse como factores de riesgo de malnutrición (AU)

Children’s diet in our country seems to be deficient in fruits and vegetables and rich in hyper caloric food. The purpose of this study is to access intake frequency of food groups in school children of our environment and the influence gender and ethnicity pose over it as well. We have evaluated the socioeconomic and demographic characteristics, lifestyles and the intake frequency of food groups in a population of 383 2nd, 3rd and 4th grade children from elementary school. Boys consume more daily servings of food rich in carbohydrates (4.38 ± 1.6 vs. 3.97 ± 1.4; p=0.03) and more dairy products (3.23 ± 1.1 vs. 2.83 ± 1.0; p= 0.002) than girls, and, on the other hand, girls eat more candy than boys (2.81 ± 3.9 vs. 2.01 ± 2.3 servings per week; p= 0.03). A high percentage of children did not meet regular recommended food percentages, both by deficiency: fruits and vegetables (78.1%), dairy products (43.4%) and carbohydrates (42.8%); and by excess: protein food (8.1%), pastries (21.2%), candy (18.9%), and sodas/snacks (8.7%). Children belonging to a certain ethnic group consume significantly less dairy products, protein products and fruits/vegetables; and, at the same time, more pastries, candy and sodas/snacks than children that do not belong to a specific ethnic group. Two significant associations (p <0.01) have been found in the analysis of the relationship between different food groups: 1) fruits and vegetables intake was associated with a higher consumption of carbohydrates and fish, and with alower consumption of sodas/snacks and time watching TV; and2) pastry intake was associated with a higher consumption of sodas/snacks and sweets. The study concludes that gender and ethnicity are factors that influence the school children´s diet and they shall be considered as risk factors for malnutrition (AU)

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.

Effect of stimulus frequency and stimulation site on the N1m response of the human auditory cortex.

The aim of the present study was to investigate the functional organization of the auditory cortex for pure tones of 1, 2, 4, 6, 8 and 12 kHz. Ten subjects were tested with a whole-head magnetometer (151 channels). The location, latency and amplitude of the generators of the N1m (the main component of the response, peaking approximately at 100 ms) were explored simultaneously in the right and left hemispheres under monaural stimulation. Our results revealed that tonotopy is a rather complex functional organization of the auditory cortex. From 1 to 12 kHz, tonotopic maps were found for contralateral as well as for ipsilateral stimulation: N1m generators were found to be tonotopically organized mainly in an anterior-posterior direction in both hemispheres, whatever the stimulated ear, but also in an inferior-superior direction in the right hemisphere. Furthermore, latencies were longer in the left than in the right hemisphere. Two different representations of spectral distribution were found in the right auditory cortex: one for ipsilateral and one for contralateral stimulation.

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.

Perceptual correlates of neural plasticity related to spontaneous otoacoustic emissions?

The inner ear contains receptor cells that oscillate spontaneously, generating waves that propagate backward in the cochlea, ultimately causing sound to be radiated into the ear canal--the spontaneous otoacoustic emissions (SOAEs). Except in rare conditions, these internally generated signals appear to go unheard. The intensity of SOAEs admittedly hovers near the threshold of detection, but they are essentially continuous and perhaps last a lifetime. The hypothesis is tested that the frequency difference limen (DL(F)) is affected by SOAEs. The results show that the DL(F) systematically improves near SOAE frequencies, determined ipsi- or contralaterally to the SOAEs, arguing for a central effect. The results are discussed in the context of central plasticity.

An auditory negative after-image as a human model of tinnitus.

The Zwicker tone (ZT) is an auditory after-image, i.e. a tonal sensation that occurs following the presentation of notched noise. In the present study, the hypothesis that neural lateral inhibition is involved in the generation of this auditory illusion was investigated in humans through differences in perceptual detection thresholds measured following broadband noise, notched noise, and low-pass noise stimulation. The detection thresholds were measured using probe tones at several frequencies, within as well as outside the suppressed frequency range of the notched noise, and below as well as above the corner frequency of the low-pass noise. Thresholds measured after broadband noise using a sequence of four 130-ms probe tones (with a 130-ms inter-burst interval) proved to be significantly smaller that those measured using the same probe tones after notched noise at frequencies falling within the notch, but larger for frequencies on the outer edges of the noise. Thresholds measured following low-pass noise using the same sequence of probe tones were found to be smaller at frequencies slightly above the corner, but larger at lower, neighboring frequencies. This pattern of results is consistent with the hypothesis that the changes in auditory sensitivity induced by stimuli containing sharp spectral contrasts reflect lateral inhibition processes in the auditory system. The potential implications of these findings for the understanding of the mechanisms underlying the generation of auditory illusions like the ZT or tinnitus are discussed.

Towards an objectification by classification of tinnitus.

OBJECTIVE: The objectives of this study are to identify the presence of tinnitus and classify its different forms, in terms of changes in noise. METHODS: Late auditory evoked responses (LAERs) were recorded from Fz in response to 1000 Hz tone bursts of various intensities, in 13 tinnitus-free subjects and in 25 tinnitus sufferers (16 bilateral and 9 unilateral tinnitus sufferers). A classification of different forms of tinnitus, in terms of changes in noise, was also undertaken. N1-P2 component amplitudes and N1 and P2 latencies were measured. RESULTS: Objective identification of the affected ear in unilateral tinnitus sufferers was found feasible on the basis of N1-P2 intensity-dependence and N1-P2 amplitude. The bilateral tinnitus group was found to differ from controls by greater intensity-dependence of the N1-P2 component and shorter N1 latency. These characteristics varied with tinnitus type: a classification on the basis of intensity-dependence and latencies proved feasible. The group of patients showing improved tinnitus in noise had greater intensity-dependence and longer N1 latency than did the group showing aggravated tinnitus in noise. CONCLUSIONS: Data are discussed in light of the inhibitory role of frontal cortex on the sensory inputs and the modulatory function of central serotonergic system on the processing of auditory information.

Differential involvement of the lateral and medial divisions of the septal area on spatial learning processes as revealed by intracranial self-administration of morphine in mice.

The present study was conducted to investigate the effects of morphine self-administration into either the medial or lateral divisions of the septal region on spatial discrimination abilities in mice. To this end, BALB/c mice received a dose of 5 ng/50 nl of morphine sulfate, via a stainless steel injection cannula, inserted into either the medial septal area (MS) or the lateral septal nucleus (LS), when they are close to the end of one of the two choice arms of a Y-maze (acquisition period). In these conditions a discrimination between the reinforced arm and the neutral arm is acquired in MS as well as in LS mice. However both acquisition and subsequent extinction (vehicle only available) was more rapid in the LS group than in the MS group. Moreover, during the extinction period, numerous escape attempts from the Y-maze were observed for MS mice. When the dose of morphine was raised to 50 ng the pattern of acquisition was unchanged in the LS group. In contrast animals of the MS group learned to avoid the arm where the higher dose of morphine was delivered thus allowing us to conclude that in MS animals the drug effect became aversive at this higher dose. This possibility was directly investigated in a second experiment by closing the access to the neutral arm. Thus, for a 5-ng dose the rewarding effect of morphine was demonstrated in both MS and LS groups by the decrease of self-administration latencies which, furthermore, were notably lower than in the discrimination situation. Moreover, with the dose of 50 ng of morphine the latencies were identical for the two groups and at their lowest value thus indicating that morphine had similar appetitive effects in MS as well as in LS mice in this situation. Thus, the previously observed deficit of MS subjects, including escape attempts, disappeared when the dose of morphine was raised and the experimental context simplified. These results which demonstrate differential functional properties of these two septal divisions are discussed in terms of conflict resulting from the strongly appetitive effects of the morphine which induces, in parallel, deleterious consequences on cognitive processing in MS self-injected mice.