Altered Glymphatic Function in Tinnitus: Associations With Cognition and Effects of rTMS

Objectives: To determine if tinnitus is associated with glymphatic system dysfunction and cognitive decline and whether repetitive transcranial magnetic stimulation (rTMS) treatment associates with an improvement in glymphatic function. Methods: We compared glymphatic function in tinnitus patients and healthy controls (HCs) using multimodal MRI indices. Multimodal MRI analyses of choroid plexus volume (CPV), enlarged perivascular space (EPVS), diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, and free water (FW). Tinnitus patients received repetitive transcranial magnetic stimulation (rTMS) and the changes in their tinnitus handicap questionnaire (THQ) scores were then correlated with changes in glymphatic function. Results: Tinnitus patients exhibited reduced DTI-ALPS indices (median, 1.51 vs. 1.55, p = 0.008, effect size = 0.242) and increased CPV (median, 2.39 vs. 2.10, p = 0.026, effect size = −0.203) compared to HCs. Elevated CPV was correlated with impaired executive function (TMT-B: r = 0.197, p = 0.033), while the reduction of the ALPS index was correlated with increased tinnitus severity (THQ: r = −0.340, p = 0.010). ROC analysis showed DTI-ALPS-mean optimally discriminated tinnitus patients from HCs (AUC = 0.896). Treatment of tinnitus patients with rTMS showed a significant decrease in FW values (median, 0.30 vs. 0.29, p = 0.007, effect size = 0.631) and a significant increase in the ALPS-index (mean, 1.35 vs. 1.37, p = 0.013, effect size = 0.653). Conclusion: Our findings suggest that glymphatic dysfunction is associated with tinnitus, highlighting a potential link that requires confirmation in longitudinal and mechanistic studies. rTMS treatment is related to reduced tinnitus severity and enhanced glymphatic function, suggesting its therapeutic potential. Level of Evidence: 3.