Comparing the electrophysiological effects of traumatic noise exposure between rodents

Noise-induced hearing deficits are important health problems in the industrialized world. As the underlying physiological dysfunctions are not well understood, research in suitable animal models is urgently needed. Three rodent species (Mongolian gerbil, rat and mouse) were studied to compare the temporal dynamics of noise-induced hearing loss after identical procedures of noise exposure. Auditory brainstem responses (ABRs) were measured before, during and up to eight weeks after noise exposure for threshold determination and ABR waveform analysis. Trauma induction with stepwise increasing sound pressure level was interrupted by five interspersed ABR measurements. Comparing short- and long-term dynamics underlying the following noise-induced hearing loss revealed diverging time courses between the three species. Hearing loss occurred early on during noise exposure in all three rodent species at or above trauma frequency. Initial noise level (105 dB SPL) was most effective in rats while the delayed level-increase to 115 dB SPL affected mice much stronger. Induced temporary threshold shifts in rats and mice were larger in animals with lower pre-trauma ABR thresholds. The increase in activity (gain) along the auditory pathway was derived by comparing the amplitudes of short- and long-latency ABR waveform components. Directly after trauma, significant effects were found for rats (decreasing gain) and mice (increasing gain) while gerbils revealed high individual variability in gain changes. Taken together, our comparative study revealed pronounced species-specific differences in the development of noise-induced hearing loss and the related processing along the auditory pathway.

Pyroptosis Accelerates Spiral Ganglion Neuronal Degeneration Induced by Aminoglycosides in the Cochlea

Background In aminoglycoside-induced hearing loss, damage to spiral ganglion neurons (SGNs) accelerates gradually after the acute outer hair cell death, accompanied by macrophage infiltration and cytokine release. Pyroptosis plays a critical role in neurodegenerative diseases. Here, we explored the potential role of pyroptosis in SGN degeneration. Methods C57BL/6J mice were randomly divided into a kanamycin plus furosemide group and saline control group. Auditory functions were evaluated by auditory brainstem response tests conducted before treatment and at 1, 5, 15, and 30 days after treatment. HCs and SGNs were assessed for morphological alterations. SGNs were subjected to RNA sequencing and mRNA and protein analyses of NLRP3 inflammasome-related molecules. Macrophage activation was evaluated based on morphological and mRNA alterations. The effect of NLRP3 inhibition on SGN survival after kanamycin treatment was evaluated in organ explant cultures treated with Mcc950, a specific inhibitor of the NLRP3 inflammasome. Results Kanamycin and furosemide administration led to irreversible deterioration of the auditory brainstem response threshold, accompanied by acute loss of outer hair cells and gradually progressive loss of inner hair cells. SGNs showed a progressive decrease in quantity, as well as swelling and membrane rupture, at 15 and 30 days. RNA sequencing of SGNs showed that inflammation and immune-related responses were significantly upregulated, as was the expression of the inflammasome-related gene NLRP3. During 30 days of kanamycin exposure, the canonical pyroptosis pathway was constantly activated in SGNs. Activation and infiltration of microglia-like cells/macrophages, and increased production of cytokines, hallmarks of neuroinflammation, were also observed. Mcc950 significantly ameliorated SGN degeneration by inhibiting NLRP3 expression and promoting release of interleukins 1β and 18. Conclusions Pyroptosis causes cell death during aminoglycoside-induced SGN degeneration. Activation of the NLRP3 inflammasome leads to a cascade of inflammatory events in SGNs. Inhibition of the NLRP3 inflammasome significantly alleviates SGN damage, suggesting that it could serve as a new molecular target for the treatment of aminoglycoside-induced SGN degeneration.

Diffusion Tensor Imaging of Auditory Pathway in Patients With Crigler-Najjar Syndrome Type I: Correlation With Auditory Brainstem Response

Aim: To evaluate the role of diffusion tensor imaging of the auditory pathway in patients with Crigler Najjar syndrome type I and its relation to auditory brainstem response. Methods: Prospective study was done including 12 patients with Crigler Najjar syndrome type I and 10 age- and sex-matched controls that underwent diffusion tensor imaging of brain. Mean diffusivity and fractional anisotropy at 4 regions of the brain and brainstem on each side were measured and correlated with the results of auditory brainstem response for patients. Results: There was significantly higher mean diffusivity of cochlear nucleus, superior olivary nucleus, inferior colliculus, and auditory cortex of patients versus controls on both sides for all regions ( P = .001). The fractional anisotropy of cochlear nucleus, superior olivary nucleus, inferior colliculus, and auditory cortex of patients versus controls was significantly lower, with P values of, respectively, .001, .001, .003, and .001 on the right side and .001, .001, .003, and .001 on left side, respectively. Also, a negative correlation was found between the maximum bilirubin level and fractional anisotropy of the left superior olivary nucleus and inferior colliculus of both sides. A positive correlation was found between the mean diffusivity and auditory brainstem response wave latency of the right inferior colliculus and left cochlear nucleus. The fractional anisotropy and auditory brainstem response wave latency of the right superior olivary nucleus, left cochlear nucleus, and inferior colliculus of both sides were negatively correlated. Conclusion: Diffusion tensor imaging can detect microstructural changes in the auditory pathway in Crigler Najjar syndrome type I that can be correlated with auditory brainstem response.

Effect of Ischemia-Induced Cochlear Inflammation on Auditory Responses in Male Rats

Background and Aim: Ischemic injury is a major cause of hearing loss and oxidative stress is an important part of ischemic injury. The goal of this study was to evaluate the cochlear oxidative stress effect on auditory responses in male rats. Methods: Cochlear oxidative stress was induced by bilateral carotid artery occlusion for 20 minutes. The rats were evaluated by biochemical inflammatory factors tumor necrosis factor-α [TNF-α] and C-reactive protein (CRP) in the day before and 1st, 4th, and 7th days following surgery. The auditory brainstem response (ABR) and electrocochleography (ECochG) were evaluated on the day before surgery and 14th, 21th and 28th days after surgery. Results: TNF-α and CRP levels concentrations increased one day after ischemia and subsequently decreased on the 7th day. The click and tone burst evoked ABR showed increased thresholds on day14th, 21th, and 28th. The highest threshold was recorded on day14th. The ECochG results also were abnormal for 55%, 70%, and 45% of cases on day 14th, 21th, and 28th, respectively. Conclusion: Cochlear oxidative stress affects hearing sensitivity. The ABR shows elevated thresholds and abnormal ECochG was found in many cases.

Evaluation of Cochlear Synaptopathy in Tinnitus Patients with Normal Hearing UsingAuditory Brainstem Response and Electrocochleography Tests

Background and Aim: Tinnitus is defined a phantom sound percept. Few studies have examined the occurrence of synaptopathy in tinnitus patients utilizing a battery of tests that indicate synaptopathy. This study aimed to investigate the role of synaptopathy in tinnitus production and compare the various characteristics of the auditory brainstem response (ABR) test and electrocochleography (ECochG) in normal-hearing people with and without tinnitus. Methods: This cross-sectional study was conducted on 34 normal-hearing individuals, 20 without tinnitus as controls (11 females and 9 males) and 14 with tinnitus (8 females and 6 men). The test components (amplitude, growth and slope of wave I, V/I ratio, action potential (AP) amplitude, and summating potential (SP)/AP) ratio were recorded during the ABR and ECochG tests for each subject. Results: The control group had higher mean values of amplitude, growth and slope of wave I, and AP amplitude compared to the tinnitus group, and this difference was statistically significant (p<0.05). The mean V/I ratio and SP/AP ratio were lower in the control group than in the tinnitus group, and this difference was statistically significant (p<0.05). Conclusion: The significant difference in the parameters of ABR and ECochG tests between normal-hearing people with and without tinnitus indicates that these parameters can be used to evaluate the presence of synaptopathy in tinnitus patients. These findings suggest the need for proper interpretation of the results of ABR and ECochG tests in tinnitus patients with a focus on the parameters indicating synaptopathy.

Neural Measures of Pitch Processing in EEG Responses to Running Speech

Linearized encoding models are increasingly employed to model cortical responses to running speech. Recent extensions to subcortical responses suggest clinical perspectives, potentially complementing auditory brainstem responses (ABRs) or frequency-following responses (FFRs) that are current clinical standards. However, while it is well-known that the auditory brainstem responds both to transient amplitude variations and the stimulus periodicity that gives rise to pitch, these features co-vary in running speech. Here, we discuss challenges in disentangling the features that drive the subcortical response to running speech. Cortical and subcortical electroencephalographic (EEG) responses to running speech from 19 normal-hearing listeners (12 female) were analyzed. Using forward regression models, we confirm that responses to the rectified broadband speech signal yield temporal response functions consistent with wave V of the ABR, as shown in previous work. Peak latency and amplitude of the speech-evoked brainstem response were correlated with standard click-evoked ABRs recorded at the vertex electrode (Cz). Similar responses could be obtained using the fundamental frequency (F0) of the speech signal as model predictor. However, simulations indicated that dissociating responses to temporal fine structure at the F0 from broadband amplitude variations is not possible given the high co-variance of the features and the poor signal-to-noise ratio (SNR) of subcortical EEG responses. In cortex, both simulations and data replicated previous findings indicating that envelope tracking on frontal electrodes can be dissociated from responses to slow variations in F0 (relative pitch). Yet, no association between subcortical F0-tracking and cortical responses to relative pitch could be detected. These results indicate that while subcortical speech responses are comparable to click-evoked ABRs, dissociating pitch-related processing in the auditory brainstem may be challenging with natural speech stimuli.