Electrophysiological and molecular changes following neuroprotective placental protein administration on tinnitus-induced rats.

Objective: Despite 6%-20% of the adult population suffering from tinnitus, there is no standard treatment for it. Placenta extract has been used for various therapeutic purposes, including hearing loss. Here, we evaluate the effect of a novel neuroprotective protein composition (NPPC) extract on electrophysiological and molecular changes in the medial geniculate body (MGB) of tinnitus-induced rats. Methods: To evaluate the protein analysis by western blot, the rats were divided into three groups: (1) saline group (intraperitoneal injection of 200 mg/kg saline twice a day for 28 consecutive days, (2) chronic Na-Sal group received sodium salicylate as in the first group, and (3) chronic treatment group (received salicylate 200 mg/kg twice daily for 2 weeks, followed by 0.4 mg NPPC daily from day 14 to day 28). Single-unit recordings were performed on a separate group that was treated as in group 4. Gap-prepulse inhibition of the acoustic startle (GPIAS) and pre-pulse inhibition (PPI) was performed to confirm tinnitus in all groups at the baseline, 14th and 28th days. Results: Western blot analysis showed that the expression of γ-Aminobutyric acid Aα1 subunit (GABA Aα1), N-methyl-d-aspartate receptor subtype 2B (NR2B or NMDAR2B), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors subunit GluR1 (GluR1), and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors subunit GluR2 (GluR2) decreased after Na-Sal injection, while NPPC upregulated their expression. MGB units in rats with tinnitus showed decreased spontaneous firing rate, burst per minute, and a spike in a burst. After NPPC administration, neural activity patterns showed a significant positive effect of NPPC on tinnitus. Conclusion: NPPC can play an effective role in the treatment of tinnitus in salicylate-induced rats, and MGB is one of the brain areas involved in these processes. Level of Evidence: NA.

The human neuroprotective placental protein composition suppressing tinnitus and restoring auditory brainstem response in a rodent model of sodium salicylate-induced ototoxicity.

The effect of neuroprotective placental protein composition (NPPC) on the suppression of tinnitus and the restoration of the auditory brainstem response (ABR) characteristics was explored in tinnitus-induced rats. The animals were placed into two groups: (1) the study group, rats received sodium salicylate (SS) at the dose of 200 mg/kg twice a day for two weeks, and then 0.4 mg of the NPPC per day, between the 14th and 28th days, (2) the placebo group, rats received saline for two weeks, and then the NPPC alone between the 14th and 28th days. The gap pre-pulse inhibition of the acoustic startle (GPIAS), the pre-pulse inhibition (PPI), and the ABR assessments were performed on animals in both groups three times (baseline, day 14, and 28). The GPIAS value declined after 14 consecutive days of the SS injection, while NPPC treatment augmented the GPIAS score in the study group on the 28th day. The PPI outcomes revealed no significant changes, indicating hearing preservation after the SS and NPPC administrations. Moreover, some changes in ABR characteristics were observed following SS injection, including (1) higher ABR thresholds, (2) lowered waves I and II amplitudes at the frequencies of 6, 12, and 24 kHz and wave III at the 12 kHz, (3) elevated amplitude ratios, and (4) prolongation in brainstem transmission time (BTT). All the mentioned variables returned to their normal values after applying the NPPC. The NPPC use could exert positive therapeutic effects on the tinnitus-induced rats and improve their ABR parameters.

Acoustic and optoacoustic stimulations in auditory brainstem response test in salicylate induced tinnitus.

As a common debilitating disorder worldwide, tinnitus requires objective assessment. In the auditory brainstem response (ABR) test, auditory potentials can be evoked by acoustic or optoacoustic (induced by laser light) stimulations. In order to use the ABR test in the objective assessment of tinnitus, in this study, acoustic ABR (aABR) and optoacoustic ABR (oABR) were compared in the control and tinnitus groups to determine the changes caused by sodium salicylate (SS)-induced tinnitus in rat. In both aABR and oABR, wave II was the most prominent waveform, and the amplitude of wave II evoked by oABR was significantly higher than that of aABR. Brainstem transmission time (BTT), which represents the time required for a neural stimulation to progress from the auditory nerve ending to the inferior colliculus, was significantly shorter in oABR. In the tinnitus group, there was a significant increase in the threshold of both ABRs and a significant decrease in the amplitude of wave II only in the oABR. Based on our findings, the ABR test has the potential to be used in the assessment of SS-induced tinnitus, but oABR has the advantages of producing more prominent waveforms and significantly reducing the amplitude of wave II in tinnitus.

Aberrant Frequency Related Change-Detection Activity in Chronic Tinnitus.

Tinnitus is the perception of sound without the occurrence of an acoustic event. The deficit in auditory sensory or echoic memory may be the cause of the perception of tinnitus. This study considered the mismatch negativity (MMN) to investigate the potential difference between and within groups of persons with normal hearing (NH) and tinnitus. Using an auditory multi-feature paradigm to elicit the MMN, this study considered the MMN peak amplitude at two central frequencies for two MMN subcomponents. These central frequencies were 1 and 5 kHz, which the latter was closer to the perceived tinnitus frequency in the group with tinnitus. The deviants were higher frequency, lower frequency, higher intensity, lower intensity, duration, location (left), location (right), and gap. The pure tone audiometry (PTA) test and distortion product otoacoustic emissions (DPOAE) test showed no meaningful difference between the two groups. For the frontal subcomponent, the mean amplitudes of the MMN peak for the two groups illustrated less negative meaningful MMN peak amplitudes in the group of persons with tinnitus. For the supratemporal component at 5 kHz central frequency, amplitudes were lower for the group of persons with tinnitus, whereas for the central frequency of 1 kHz, most deviants exhibited meaningful differences. Additionally, within-group comparisons indicated that mean amplitudes for both groups were more negative at the central frequency of 1 kHz for the frontal MMN subcomponent. In comparison, the supratemporal component illustrated a lower peak amplitude at 5 kHz central frequency in the group of persons with tinnitus and no difference in the NH group, which is a unique observation of this study. Results of the between-groups are in accordance with previous studies and within-group comparisons consider the probability of decreasing the change detection capability of the brain. The results of this study indicate that increasing the frequency of the stimuli close to the tinnitus perceived frequencies decreases the prediction error, including the prediction error of the silence. Such a decrease may cause the prediction error of the spontaneous neural activity in the auditory pathway to exceed the silence prediction error, and as a result, increases the probability of occurrence of tinnitus in higher frequencies according to the predictive coding model.

The potential role of auditory prediction error in decompensated tinnitus: An auditory mismatch negativity study.

INTRODUCTION: Some tinnitus subjects habituate to their tinnitus but some others do not and complain of its annoyance tremendously. Normal sensory memory and change detection processes are needed for detecting the tinnitus signal as a prediction error and habituation to tinnitus. The purpose of this study was to compare auditory mismatch negativity as the index of sensory memory and change detection among the studied groups to search for the factors involving in the perception of tinnitus and preventing habituation in decompensated tinnitus subjects. METHODS: Electroencephalography was recorded from scalp electrodes in compensated tinnitus, decompensated tinnitus, and no tinnitus control subjects. Mismatch negativity was obtained using the oddball paradigm with frequency, duration, and silent gap deviants. Amplitude, latency, and area under the curve of mismatch negativities were compared among the three studied groups. RESULTS: The results showed lower mismatch negativity amplitude and area under the curve for the higher frequency deviant and for the silent gap deviant in decompensated tinnitus group compared to normal control and compensated tinnitus group. CONCLUSIONS: This study revealed a deficit in sensory memory and change detection processing in decompensated tinnitus subjects. This causes persistent prediction errors; tinnitus signal is consistently detected as a new signal and activates the brain salience network and consequently prevents habituation to tinnitus. Mismatch negativity is proposed as an index for monitoring tinnitus rehabilitation.

Cognitive Memory Comparison Between Tinnitus and Normal Cases Using Event-Related Potentials.

About 20 percent of people above 60 years old suffer from tinnitus though no definitive treatment has been found for it. Evaluation of electrical brain activity using Event-Related Potentials (ERPs) is one of the methods to investigate the underlying reasons of tinnitus perception. Previous studies using ERPs suggest that the precognitive memory in tinnitus groups is negatively affected in comparison to the normal hearing groups. In this study, cognitive memory has been assessed using visual and auditory P300 response with oddball paradigm. Fifteen chronic tinnitus subjects and six normal hearing subjects participated in the experiment. T-test with significance level of 0.05 was applied on amplitude and latency of auditory and visual P300 for all electroencephalography (EEG) channels separately to compare tinnitus and normal hearing groups where the tinnitus group showed meaningful lower amplitude of auditory P300 peak in three EEG channels.

Brain Waves Evaluation of Sound Therapy in Chronic Subjective Tinnitus Cases Using Wavelet Decomposition.

Management and treatment of subjective tinnitus is an ongoing focus of research activities. One of the most viable assessments of such treatment is the evaluation of brain activity in addition to patient response and clinical assessment. This study focuses on sound therapy and evaluation of patients' electroencephalogram (EEG) in order to verify the potency of this approach. Broadband sound therapy was applied to nineteen participants aging from 25 to 64 and suffering from chronic subjective tinnitus to study the difference of brain activity, a) before fake treatment, b) after fake treatment and c) after the main treatment, using EEG and Visual Analog Scale (VAS) for evaluating Residual Inhibition (RI). Four features were extracted using 4-level wavelet decomposition with Symlet 8 as its mother wavelet. For the "After the main treatment" stage, the mean value of wavelet coefficients for the last wavelet level, which corresponded to delta band of EEG, was lower in the FC3 channel based on Two-Sample T-Test with significance level of 0.01, as compared to the same channel of the "before the treatment" stage, for cases in which decreased tinnitus loudness were reported.