Zinc Supplement Modifies Auditory Brainstem Responses in Patients with Tinnitus

Introduction: Zinc is an essential element for human homeostasis being clearly related to almost all metabolic pathways. It is found in some neural circuitries, probably acting as a modulator of glutamatergic excitatory synapsis. In the auditory system its presence has been demonstrated within the cochlea and cochlear nuclei. Tinnitus symptoms are correlated to zinc physiology, and it has been postulated that the oligoelement could be used as an alternative treatment for this clinical situation. Aim: This study has evaluated the brainstem responses (ABR) in patients who suffer from chronic idiophatic tinnitus, before and after being treated with zinc. Neural transmissions in the brainstem auditory structures were also compared in both conditions. Materials and Methods: Forty-one patients (22 with tinnitus and 19 controls, groups I and II, respectively) were included in the study and submitted to anamnesis, otorhinolaryngologic examinations, biochemical evaluation and audiological tests. Group I patients received an specific zinc formulation for 90 days. ABR tests were performed at the beginning of the study and at the end of the zinc treatment. Results: First ABR tests showed no differences between the groups, but on the second evaluation there was a significant prolongation of the wave V latency and an enlargement of wave V amplitude shown in group I. Conclusion: Treatment with systemic zinc could change some aspects of auditory neurotransmission in the brainstem.

Postnatal developmental expression of the PDZ scaffolds Na+-H+ exchanger regulatory factors 1 and 2 in the rat cochlea

Sensory transduction in the mammalian cochlea requires the maintenance of specialized fluid compartments with distinct ionic compositions. This is achieved by the concerted action of diverse ion channels and transporters, some of which can interact with the PDZ scaffolds, Na+-H+ exchanger regulatory factors 1 and 2 (NHERF-1, NHERF-2). Here, we report that NHERF-1 and NHERF-2 are widely expressed in the rat cochlea, and that their expression is developmentally regulated. Reverse transcription/polymerase chain reaction (RT-PCR) and Western blotting initially confirmed the RNA and protein expression of NHERFs. We then performed immunohistochemistry on cochlea during various stages of postnatal development. Prior to the onset of hearing (P8), NHERF-1 immunolabeling was prominently polarized to the apical membrane of cells lining the endolymphatic compartment, including the stereocilia and cuticular plates of the inner and outer hair cells, marginal cells of the stria vascularis, Reissner's epithelia, and tectorial membrane. With maturation (P21, P70), NHERF-1 immunolabeling was reduced in the above structures, whereas labeling increased in the apical membrane of the interdental cells of the spiral limbus and the inner and outer sulcus cells, Hensen's cells, the inner and outer pillar cells, Deiters cells, the inner border cells, spiral ligament fibrocytes, and spiral ganglion neurons (particularly type II). NHERF-1 expression in strial basal and intermediate cells was persistent. NHERF-2 immunolabeling was similar to that for NHERF-1 during postnatal development, with the exception of expression in the synaptic regions beneath the outer hair cells. NHERF-1 and NHERF-2 co-localized with glial fibrillary acidic protein and vimentin in glia. The cochlear localization of NHERF scaffolds suggests that they play important roles in the developmental regulation of ion transport, homeostasis, and auditory neurotransmission.

Increased bursting glutamatergic neurotransmission in an auditory forebrain area of the zebra finch (Taenopygia guttata) induced by auditory stimulation

The caudomedial nidopallium (NCM) is a telencephalic area involved in auditory processing and memorization in songbirds, but the synaptic mechanisms associated with auditory processing in NCM are largely unknown. To identify potential changes in synaptic transmission induced by auditory stimulation in NCM, we used a slice preparation for path-clamp recordings of synaptic currents in the NCM of adult zebra finches (Taenopygia guttata) sacrificed after sound isolation followed by exposure to conspecific song or silence. Although post-synaptic GABAergic and glutamatergic currents in the NCM of control and song-exposed birds did not present any differences regarding their frequency, amplitude and duration after song exposure, we observed a higher probability of generation of bursting glutamatergic currents after blockade of GABAergic transmission in song-exposed birds as compared to controls. Both song-exposed males and females presented an increase in the probability of the expression of bursting glutamatergic currents, however bursting was more commonly seen in males where they appeared even without blocking GABAergic transmission. Our data show that song exposure changes the excitability of the glutamatergic neuronal network, increasing the probability of the generation of bursts of glutamatergic currents, but does not affect basic parameters of glutamatergic and GABAergic synaptic currents.

Glutamatergic neurotransmission mediated by NMDA receptors in the inferior colliculus can modulate haloperidol-induced catalepsy

The inferior colliculus (IC) is primarily involved in the processing of auditory information, but it is distinguished from other auditory nuclei in the brainstem by its connections with structures of the motor system. Functional evidence relating the IC to motor behavior derives from experiments showing that activation of the IC by electrical stimulation or excitatory amino acid microinjection causes freezing, escape-like behavior, and immobility. However, the nature of this immobility is still unclear. The present study examined the influence of excitatory amino acid-mediated mechanisms in the IC on the catalepsy induced by the dopamine receptor blocker haloperidol administered systemically (1 or 0.5 mg/kg) in rats. Haloperidol-induced catalepsy was challenged with prior intracollicular microinjections of glutamate NMDA receptor antagonists, MK-801 (15 or 30 mmol/0.5 mu l) and AP7 (10 or 20 nmol/0.5 mu l), or of the NMDA receptor agonist N-methyl-D-aspartate (NMDA, 20 or 30 nmol/0.5 mu l). The results showed that intracollicular microinjection of MK-801 and AP7 previous to systemic injections of haloperidol significantly attenuated the catalepsy, as indicated by a reduced latency to step down from a horizontal bar. Accordingly, intracollicular microinjection of NMDA increased the latency to step down the bar. These findings suggest that glutamate-mediated mechanisms in the neural circuits at the IC level influence haloperidol-induced catalepsy and participate in the regulation of motor activity. (C) 2010 Published by Elsevier B.V.

Central Auditory Processing Outcome After Stroke In Children.

To investigate central auditory processing in children with unilateral stroke and to verify whether the hemisphere affected by the lesion influenced auditory competence. 23 children (13 male) between 7 and 16 years old were evaluated through speech-in-noise tests (auditory closure); dichotic digit test and staggered spondaic word test (selective attention); pitch pattern and duration pattern sequence tests (temporal processing) and their results were compared with control children. Auditory competence was established according to the performance in auditory analysis ability. Was verified similar performance between groups in auditory closure ability and pronounced deficits in selective attention and temporal processing abilities. Most children with stroke showed an impaired auditory ability in a moderate degree. Children with stroke showed deficits in auditory processing and the degree of impairment was not related to the hemisphere affected by the lesion.

Temporal Auditory Processing And Phonological Awareness In Children With Benign Epilepsy With Centrotemporal Spikes.

The aim of this research was to analyze temporal auditory processing and phonological awareness in school-age children with benign childhood epilepsy with centrotemporal spikes (BECTS). Patient group (GI) consisted of 13 children diagnosed with BECTS. Control group (GII) consisted of 17 healthy children. After neurological and peripheral audiological assessment, children underwent a behavioral auditory evaluation and phonological awareness assessment. The procedures applied were: Gaps-in-Noise test (GIN), Duration Pattern test, and Phonological Awareness test (PCF). Results were compared between the groups and a correlation analysis was performed between temporal tasks and phonological awareness performance. GII performed significantly better than the children with BECTS (GI) in both GIN and Duration Pattern test (P < 0.001). GI performed significantly worse in all of the 4 categories of phonological awareness assessed: syllabic (P = 0.001), phonemic (P = 0.006), rhyme (P = 0.015) and alliteration (P = 0.010). Statistical analysis showed a significant positive correlation between the phonological awareness assessment and Duration Pattern test (P < 0.001). From the analysis of the results, it was concluded that children with BECTS may have difficulties in temporal resolution, temporal ordering, and phonological awareness skills. A correlation was observed between auditory temporal processing and phonological awareness in the suited sample.

Operant measurement of auditory threshold in prelingually deaf users of cochlear implants: II

Two experiments evaluated an operant procedure for establishing stimulus control using auditory and electrical stimuli as a baseline for measuring the electrical current threshold of electrodes implanted in the cochlea. Twenty-one prelingually deaf children, users of cochlear implants, learned a Go/No Go auditory discrimination task (i.e., pressing a button in the presence of the stimulus but not in its absence). When the simple discrimination baseline became stable, the electrical current was manipulated in descending and ascending series according to an adapted staircase method. Thresholds were determined for three electrodes, one in each location in the cochlea (basal, medial, and apical). Stimulus control was maintained within a certain range of decreasing electrical current but was eventually disrupted. Increasing the current recovered stimulus control, thus allowing the determination of a range of electrical currents that could be defined as the threshold. The present study demonstrated the feasibility of the operant procedure combined with a psychophysical method for threshold assessment, thus contributing to the routine fitting and maintenance of cochlear implants within the limitations of a hospital setting.

Polarity-Dependent Transcranial Direct Current Stimulation Effects on Central Auditory Processing

Given the polarity dependent effects of transcranial direct current stimulation (tDCS) in facilitating or inhibiting neuronal processing, and tDCS effects on pitch perception, we tested the effects of tDCS on temporal aspects of auditory processing. We aimed to change baseline activity of the auditory cortex using tDCS as to modulate temporal aspects of auditory processing in healthy subjects without hearing impairment. Eleven subjects received 2mA bilateral anodal, cathodal and sham tDCS over auditory cortex in a randomized and counterbalanced order. Subjects were evaluated by the Random Gap Detection Test (RGDT), a test measuring temporal processing abilities in the auditory domain, before and during the stimulation. Statistical analysis revealed a significant interaction effect of time vs. tDCS condition for 4000 Hz and for clicks. Post-hoc tests showed significant differences according to stimulation polarity on RGDT performance: anodal improved 22.5% and cathodal decreased 54.5% subjects' performance, as compared to baseline. For clicks, anodal also increased performance in 29.4% when compared to baseline. tDCS presented polarity-dependent effects on the activity of the auditory cortex, which results in a positive or negative impact in a temporal resolution task performance. These results encourage further studies exploring tDCS in central auditory processing disorders.

Dysautonomia due to reduced cholinergic neurotransmission causes cardiac remodeling and heart failure

Overwhelming evidence supports the importance of the sympathetic nervous system in heart failure. In contrast, much less is known about the role of failing cholinergic neurotransmission in cardiac disease. By using a unique genetically modified mouse line with reduced expression of the vesicular acetylcholine transporter (VAChT) and consequently decreased release of acetylcholine, we investigated the consequences of altered cholinergic tone for cardiac function. M-mode echocardiography, hemodynamic experiments, analysis of isolated perfused hearts, and measurements of cardiomyocyte contraction indicated that VAChT mutant mice have decreased left ventricle function associated with altered calcium handling. Gene expression was analyzed by quantitative reverse transcriptase PCR and Western blotting, and the results indicated that VAChT mutant mice have profound cardiac remodeling and reactivation of the fetal gene program. This phenotype was attributable to reduced cholinergic tone, since administration of the cholinesterase inhibitor pyridostigmine for 2 weeks reversed the cardiac phenotype in mutant mice. Our findings provide direct evidence that decreased cholinergic neurotransmission and underlying autonomic imbalance cause plastic alterations that contribute to heart dysfunction.

Auditory processing disorder in perisylvian syndrome

We hypothesized that the processing of auditory information by the perisylvian polymicrogyric cortex may be different from the normal cortex. To characterize the auditory processing in bilateral perisylvian syndrome, we examined ten patients with perisylvian polymicrogyria (Group 1) and seven control children (Group 11). Group I was composed by four children with bilateral perisylvian polymicrogyria and six children with bilateral posterior perisylvian polymicrogyria. The evaluation included neurological and neuroimaging investigation, intellectual quotient and audiological assessment (audiometry and behavior auditory tests). The results revealed a statistically significant difference between the groups in the behavioral auditory tests, Such as, digits dichotic test, nonverbal dichotic test (specifically in right attention), and random gap detection/random gap detection expanded tests. Our data showed abnormalities in the auditory processing of children with perisylvian polymicrogyria, suggesting that perisylvian polymicrogyric cortex is functionally abnormal. We also found a correlation between the severity of our auditory findings and the extent of the cortical abnormality. (C) 2009 Elsevier B.V. All rights reserved.

Auditory lexical decisions in children with specific language impairment

This study examined spoken-word recognition in children with specific language impairment (SLI) and normally developing children matched separately for age and receptive language ability. Accuracy and reaction times on an auditory lexical decision task were compared. Children with SLI were less accurate than both control groups. Two subgroups of children with SLI, distinguished by performance accuracy only, were identified. One group performed within normal limits, while a second group was significantly less accurate. Children with SLI were not slower than the age-matched controls or language-matched controls. Further, the time taken to detect an auditory signal, make a decision, or initiate a verbal response did not account for the differences between the groups. The findings are interpreted as evidence for language-appropriate processing skills acting upon imprecise or underspecified stored representations.

Facilitation of 5-HT(1A)-mediated neurotransmission in dorsal periaqueductal grey matter accounts for the panicolytic-like effect of chronic fluoxetine

Chronic administration of antidepressants such as fluoxetine and imipramine increases the responsiveness of 5-HT(1A) receptors in dorsal periaqueductal grey matter (DPAG), a midbrain area consistently implicated in the pathogenesis of panic disorder. This effect has been related to the clinically relevant anti-panic action of these drugs. In this study we determined whether long-term administration of fluoxetine also affects 5-HT efflux in DPAG. As a comparison, the effect of chronic treatment with the anxiolytic 5-HT(1A) receptor agonist buspirone on DPAG 5-HT levels was assessed. We also investigated whether the inhibitory effect of chronic fluoxetine on escape behaviour in the rat elevated T-maze, considered as a panicolytic-like effect, is counteracted by intra-DPAG injection of the 5-HT(1A) receptor antagonist WAY 100635. Male Wistar rats were treated (1 or 21 d, i.p.) with fluoxetine, buspirone or vehicle, once daily. After treatment, 5-HT in DPAG was measured by in-vivo microdialysis coupled to HPLC. In another study, rats treated (21 d, i.p.) with either fluoxetine or vehicle also received intra-DPAG injection of WAY 100635 or saline 10 min before being tested in the elevated T-maze. Chronic, but not acute, administration of fluoxetine significantly raised extracellular levels of 5-HT in DPAG. Long-term treatment with buspirone was ineffective. In the elevated T-maze, intra-DPAG injection of WAY 100635 fully blocked the anti-escape effect of chronic administration of fluoxetine. Therefore, chronic fluoxetine facilitates 5-HT(1A)-mediated neurotransmission within DPAG and this effect accounts for the panicolytic-like effect of this antidepressant in the elevated T-maze.

GABAergic REGULATION OF AUDITORY SENSORY GATING IN LOW- AND HIGH-ANXIETY RATS SUBMITTED TO A FEAR CONDITIONING PROCEDURE

The inferior colliculus (IC) is primarily involved in the processing of acoustic stimuli, being in a position to send auditory information to motor centers that participate in behaviors such as prey catching and predators` avoidance The role of the central nucleus of the IC (CIC) on fear and anxiety has been suggested on the basis that rats are able to engage in tasks to decrease the aversiveness of CIC stimulation, increased Fos immunolabeling during diverse aversive states and increased CIC auditory evoked potentials (AEP) induced by conditioned fear stimuli Additionally it was shown that brainstem AEP, represented by wave V, for which the main generator is the IC, is increased during experimentally induced anxiety Rats segregated according to their low or high emotional reactivity have been used as an important tool in the study of fear and anxiety The IC contains a high density of GABA receptors Since the efficacy of an anxiolytic compound is a function of the animal`s anxiety level, it is possible that GABA-benzodiazepine (Bzp) agents affect LA and HA animals differently In this study we investigated the GABA-Bzp influence on the modulation of AEP in rats with low (LA) or high-anxiety (HA) levels, as assessed by the elevated plus maze test (EPM) GABA-Bzp modulation on the unconditioned AEP response was analyzed by using intra CIC injections (0 2 mu l) of the GABA-Bzp agonists muscimol (121 ng) and diazepam (30 mu g) or the GABA inhibitors bicuculline (10 ng) and semicarbazide (7 mu g) In a second experiment, we evaluate the effects of contextual aversive conditioning on AEP using foot shocks as unconditioned stimuli On the unconditioned fear paradigm GABA inhibition in creased AEP in LA rats and decreases this measure in HA counterparts Muscimol was effective in reducing AEP in both LA and HA rats Contextual fear stimuli increased the magnitude of AEP In spite of no effect obtained with diazepam in LA rats the drug inhibited AEP in HA animals The specificity of the regulatory mechanisms mediated by GABA Bzp for the ascending neurocircuits responsible for the acquisition of aversive information in LA and HA animals shed light on the processing of sensory information underlying the generation of defensive reactions (C) 2010 IBRO Published by Elsevier Ltd All rights reserved