Tinnitus is defined as the phantom perception of sound. To date, there is no curative treatment, and contemporary treatments have failed to show beneficial outcomes. Deep brain stimulation has been suggested as a potential therapy for refractory tinnitus. However, the optimal target and stimulation regimens remain to be defined. Herein, we investigated metabolic and neuronal activity changes using cytochrome C oxidase histochemistry and c-Fos immunohistochemistry in a noise trauma-induced rat model of tinnitus. We also assessed changes in neuronal activity following medial geniculate body (MGB) high-frequency stimulation (HFS). Metabolic activity was reduced in the primary auditory cortex, MGB and CA1 region of the hippocampus in noise-exposed rats. Additionally, c-Fos expression was increased in the primary auditory cortex of those animals. Furthermore, MGB-HFS enhanced c-Fos expression in the thalamic reticular nucleus. We concluded that noise trauma alters tissue activity in multiple brain areas including the auditory and limbic regions. MGB-HFS resulted in higher neuronal activity in the thalamic reticular nucleus. Given the prominent role of the auditory thalamus in tinnitus, these data provide more rationales towards targeting the MGB with HFS as a symptom management tool in tinnitus.

Tinnitus is the phantom perception of a sound, often accompanied by increased anxiety and depressive symptoms. Degenerative or inflammatory processes, as well as changes in monoaminergic systems, have been suggested as potential underlying mechanisms. Herein, we conducted the first post-mortem histopathological assessment to reveal detailed structural changes in tinnitus patients’ auditory and non-auditory brain regions. Tissue blocks containing the medial geniculate body (MGB), thalamic reticular nucleus (TRN), central part of the inferior colliculus (CIC), and dorsal and obscurus raphe nuclei (DRN and ROb) were obtained from tinnitus patients and matched controls. Cell density and size were assessed in Nissl-stained sections. Astrocytes and microglia were assessed using immunohistochemistry. The DRN was stained using antibodies raised against phenylalanine hydroxylase-8 (PH8) and tyrosine-hydroxylase (TH) to visualize serotonergic and dopaminergic cells, respectively. Cell density in the MGB and CIC of tinnitus patients was reduced, accompanied by a reduction in the number of astrocytes in the CIC only. Quantification of cell surface size did not reveal any significant difference in any of the investigated brain regions between groups. The number of PH8-positive cells was reduced in the DRN and ROb of tinnitus patients compared to controls, while the number of TH-positive cells remained unchanged in the DRN. These findings suggest that both neurodegenerative and inflammatory processes in the MGB and CIC underlie the neuropathology of tinnitus. Moreover, the reduced number of serotonergic cell bodies in tinnitus cases points toward a potential role of the raphe serotonergic system in tinnitus.

Background: Globus pharyngeus is a clinical condition, wherein, a patient senses a lump or a foreign body in the throat with a tightening or choking feeling. A strong association between globus pharyngeus and gastroesophageal reflux disease (GERD) was reported. Therefore, we sought to investigate the predictive factors of globus pharyngeus in patients with established GERD and fit a predictive scoring model for globus pharyngeus. Methods: In this case-control study, 143 patients having globus pharyngeus along with GERD (case) and 109 patients having globus pharyngeus without GERD (control) were enrolled. Data comprising demographics, comorbidities, and psychosocial stress levels were recorded. The predictive factors of globus pharyngeus in patients with GERD were unraveled, and a predictive scoring model was fit for globus pharyngeus. Results: Proton pump inhibitor usage in the case group was significantly higher compared to controls (63.63% vs 24.78%, P < 0.001), and differences in Hiatus Hernia and Stress levels were highly significant between the two groups (P < 0.001). Multivariate logistic regression revealed that variates, Hiatus Hernia, psychosocial stress, and age were highly significant (P < 0.001) independent predictors of globus pharyngeus. Using the regression coefficients of all the independent predictor variables, a predictive scoring model was fitted, which yielded an area under receiver operating characteristic (AUROC) curve of 78.9. Conclusion: Hiatus hernia, psychosocial stress, and age are significant independent predictors of globus pharyngeus in GERD, and our predictive scoring model may help in identifying patients at higher odds of experiencing globus pharyngeus and modulate treatment accordingly.