Tehran University of Medical Sciences Auditory and Vestibular Research 2423-480X 35 3 2025 09 17 225 231 Azadeh Imani Department of Cognitive Neuroscience, Institute for Cognitive Science Studies, Tehran, Iran Mohammad Nasehi Cognitive and Neuroscience Research Center, TeMS.C., Islamic Azad University, Tehran, Iran AND Department of Physiology, TeMS.C., Islamic Azad University, Tehran, Iran Hamid Jalilvand Department of Audiology, School of Rehabilitation, Shahid Beheshti University of Medical Sciences, Tehran, Iran Mohammad-Reza Zarrindast Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Solmaz Khalife Department of Physiology, TeMS.C., Islamic Azad University, Tehran, Iran 2025 07 21 2025 09 09 Background and Aim: Tinnitus is associated with increased listening effort and reduced Working Memory (WM) during speech comprehension. A practical approach to enhance cognitive processes is transcranial Direct Current Stimulation (tDCS). This study aimed to evaluate the effect of tDCS on listening effort, mental fatigue, tinnitus annoyance, WM, and expression of N-Methyl-D-Aspartate (NMDA) receptor subunits (NR1 and NR2) in the blood of individuals with tinnitus. Methods: Thirty-two chronic tinnitus participants (aged 30–60 years) were randomly assigned to intervention and control groups. The intervention group received anodal tDCS over the left Dorsolateral Prefrontal Cortex (DLPFC) with electrode on F3 for 20 minutes at 1.5 mA over 10 sessions, while the control group underwent sham tDCS. Pre- and postintervention assessments included audiometry, tympanometry, tinnitus matching, a dualtask paradigm for measuring listening effort, the visual analogue scale for measuring mental fatigue, the Tinnitus Functional Index (TFI) for measuring tinnitus annoyance, and the N-Back test for WM assessment. Western blot analysis of blood samples measured NR1 and NR2 protein expression. Results: Compared to the control group, active tDCS significantly reduced listening effort, mental fatigue, tinnitus annoyance (p<0.001) and improved WM (p<0.001). After intervention, the intervention group showed a 27% increase in NR1 and a 50% increase in NR2 expression. Conclusion: The tDCS over DLPFC can reduce listening effort, mental fatigue, and tinnitus annoyance, and enhance WM in adults with chronic tinnitus, which is associated with improved NR1/NR2 protein expression in blood. These findings highlight the potential role of tDCS in tinnitus rehabilitation. https://avr.tums.ac.ir/index.php/avr/article/view/1478