Functional Connectivity Alterations and Molecular Characterization of the Anterior Cingulate Cortex in Tinnitus Pathology without Hearing Loss.

Compared with individuals with hearing loss, tinnitus patients without hearing loss have more psychological or emotional problems. Tinnitus is closely associated to abnormal metabolism and function of the limbic system, a key brain region for emotion experience, but the underlying molecular mechanism remains unknown. Using whole-brain microvasculature dynamics imaging, the anterior cingulate cortex (ACC) is identified as a key brain region of limbic system involve in the onset of salicylate-induced tinnitus in mice. In the tinnitus group, there is enhanced purine metabolism, oxidative phosphorylation, and a distinct pattern of phosphorylation in glutamatergic synaptic pathway according to the metabolome profiles, quantitative proteomic, and phosphoproteomic data of mice ACC tissue. Electroencephalogram in tinnitus patients with normal hearing thresholds show that the functional connectivity between pregenual anterior cingulate cortex and the primary auditory cortex is significantly increased for high-gamma frequency band, which is positively correlated with the serum glutamate level. These findings indicate that ACC plays an important role in the pathophysiology of tinnitus by interacting with the primary auditory cortex and provide potential molecular targets in the ACC for tinnitus treatment.

Effect of Electrode Insertion Angle on Cochlear Implantation Outcomes in Adult and Children Patients with Sensorineural Hearing Loss.

Purpose: To determine the role played by electrode insertion angle in cochlear implantation (CI) outcomes in adult and children patients with sensorineural hearing loss (SNHL). Methods: Adults (n = 10) and children (n = 19) with SNHL undergoing CI in a tertiary specialized hospital were retrospectively enrolled. The measurements were evaluated before and after CI surgery using sound field audiometry and speech recognition tests. Questionnaires were used to assess subjective benefits. Electrode insertion angles were determined using postoperative X-rays. Results: Both adult and children patients showed significant improvements in hearing, speech performance, and audiology and speech-related quality of life after CI. The angular insertion depths of adult and children group were 323.70 ± 43.57° and 341.53 ± 57.07°, respectively, showing no significant difference. In the adult group, deeper insertion depths were found to be strongly linked to lower postoperative pure tone thresholds at 12 months and higher postoperative disyllabic Word Recognition and Sentence Recognition Scores at 6 months (all P < 0.05). In the children group, deeper insertion depth had a positive correlation with postoperative monosyllabic Word Recognition Scores 6 and 12 months after CI surgery (both P < 0.05). Multiple linear regression models were constructed to predict disyllabic Word Recognition Scores at 6 and 12 months postoperatively in the children group, in which insertion angle, duration of hearing loss, and preoperative questionnaire result were identified as dependent variables. Conclusions: Greater angular insertion depths resulted in improved hearing and speech performances after CI. The benefits of greater angular insertion depths can be found in both adult and children patients and last for at least 12 months. Clinicians are expected to determine the optimal implantation direction during CI and ensure the insertion depth to improve the speech rehabilitation of patients.

Effect of Sodium Salicylate on Calcium Currents and Exocytosis in Cochlear Inner Hair Cells: Implications for Tinnitus Generation.

Sodium salicylate is an anti-inflammatory medication with a side-effect of tinnitus. Here, we used mouse cochlear cultures to explore the effects of salicylate treatment on cochlear inner hair cells (IHCs). We found that IHCs showed significant damage after exposure to a high concentration of salicylate. Whole-cell patch clamp recordings showed that 1-5 mmol/L salicylate did not affect the exocytosis of IHCs, indicating that IHCs are not involved in tinnitus generation by enhancing their neuronal input. Instead, salicylate induced a larger peak amplitude, a more negative half-activation voltage, and a steeper slope factor of Ca2+ current. Using noise analysis of Ca2+ tail currents and qRT-PCR, we further found that salicylate increased the number of Ca2+ channels along with CaV1.3 expression. All these changes could act synergistically to enhance the Ca2+ influx into IHCs. Inhibition of intracellular Ca2+ overload significantly attenuated IHC death after 10 mmol/L salicylate treatment. These results implicate a cellular mechanism for tinnitus generation in the peripheral auditory system.