Tehran University of Medical Sciences Auditory and Vestibular Research 2423-480X 0 0 2025 09 17 1478 1478 Azadeh Imani Department of Cognitive Neuroscience, Institute for Cognitive Science Studies (ICSS), Tehran, Iran Mohammad Nasehi - Hamid Jalilvand - Mohammad-Reza Zarrindast - Solmaz Khalife - 2025 07 21 2025 09 09 Background and Aim: Tinnitus has been associated with increased listening effort and reduced working memory (WM) capacity during speech comprehension. A practical approach to enhance cognitive processes is transcranial direct current stimulation (tDCS), a non-invasive neuromodulation technique applying constant low current. Anodal tDCS increases the expression of N-methyl-D-aspartate receptor 1(NR1 and NR2) proteins in blood, which are associated with WM improvement. This study aimed to evaluate the effect of tDCS on listening effort, WM, and N-methyl-D-aspartate (NMDA) receptor subunit protein expression in blood of individuals with tinnitus. Methods: Thirty-two adults (30–60 years) were randomly assigned to experimental and control groups. The experimental group received anodal tDCS with electrodes on F3 and F4 for 20 minutes at 1.5 mA over 10 sessions, while the control group underwent electrode placement without stimulation. Pre- and post-intervention assessments included audiometry, tympanometry, tinnitus matching, listening effort evaluation (cognitive-behavioral tasks, dual-task, visual analogue scale, and tinnitus functional index), and WM assessment (N-BACK test). Blood samples were analyzed using Western blot to measure NR1 and NR2 protein expression in blood. Results: Compared to the control group, tDCS significantly reduced listening effort (p<0.001) and improved WM (p<0.001). After intervention, the experimental group showed a 27% increase in NR1 and a 50% increase in NR2 expression. Conclusion: tDCS effectively reduced listening effort and enhanced WM in individuals with chronic tinnitus. The upregulation of NR1/NR2 protein expression in blood may contribute to improved auditory-cognitive performance, highlighting the potential role of this technique in tinnitus rehabilitation. https://avr.tums.ac.ir/index.php/avr/article/view/1478