The Impact of Anodal Prefrontal Transcranial Stimulation on Listening Effort, Working Memory and the expression of N-methyl-D-aspartate receptor blood protein in patients with tinnitus
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Abstract
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.
1. Hu J, Cui J, Xu JJ, Yin X, Wu Y, Qi J. The neural mechanisms of tinnitus: A perspective from functional magnetic resonance imaging. Front Neurosci. 2021;15:621145. [DOI:10.3389/fnins.2021.621145]
2. Andersson G. Tinnitus patients with cognitive problems: Causes and possible treatments. Hear J. 2009; 62(11):27-8. [DOI:10.1097/01.HJ.0000364273.37223.ff]
3. Neff P, Simoes J, Psatha S, Nyamaa A, Boecking B, Rausch L, et al. The impact of tinnitus distress on cognition. Sci Rep. 2021; 11(1):2243. [DOI:10.1038/s41598-021-81728-0]
4. Tai Y, Husain FT. The Role of Cognitive Control in Tinnitus and Its Relation to Speech-in-Noise Performance. J Audiol Otol. 2019; 23(1):1-7. [DOI:10.7874/jao.2018.00409]
5. Rossiter S, Stevens C, Walker G. Tinnitus and its effect on working memory and attention. J Speech Lang Hear Res. 2006; 49(1):150-60. [DOI:10.1044/1092-4388(2006/012)]
6. Martins ML, Souza DDS, Cavalcante MeOB, Barboza HN, de Medeiros JF, Dos Santos Andrade SMM, et al. Effect of transcranial Direct Current Stimulation for tinnitus treatment: A systematic review and meta-analysis. Neurophysiol Clin. 2022; 52(1):1-16. [DOI:10.1016/j.neucli.2021.12.005]
7. Ghanavati E, Salehinejad MA, De Melo L, Nitsche MA, Kuo MF. NMDA receptor-related mechanisms of dopaminergic modulation of tDCS-induced neuroplasticity. Cerebral Cortex. 2022; 32(23):5478-88. [DOI:10.1093/cercor/bhac028]
8. Hoare DJ, Edmondson-Jones M, Gander PE, Hall DA. Agreement and reliability of tinnitus loudness matching and pitch likeness rating. Plos One. 2014; 9(12):e114553. [DOI:10.1371/journal.pone.0114553]
9. Meikle MB, Henry JA, Griest SE, Stewart BJ, Abrams HB, McArdle R, et al. The tinnitus functional index: Development of a new clinical measure for chronic, intrusive tinnitus. Ear Hear. 2012; 33(2):153-76. [DOI:10.1097/AUD.0b013e31822f67c0]
10. Mahdavi ME, Meymeh MH, Nazeri A, Jalilvand H, Heidari F, Fathollahzadeh F. A preliminary study on the reliability of the Persian version of the tinnitus functional index in a military population. Audit Vestib Res. 2020. [DOI:10.18502/avr.v29i2.2794]
11. Torrance GW, Feeny D, Furlong W. Visual analog scales: Do they have a role in the measurement of preferences for health states? Med Decis Making. 2001; 21(4):329-34. [DOI:10.1177/0272989X0102100408]
12. Alhanbali S, Munro KJ, Dawes P, Carolan PJ, Millman RE. Dimensions of self-reported listening effort and fatigue on a digits-in-noise task, and association with baseline pupil size and performance accuracy. Int J Audiol. 2021; 60(10):762-72. [DOI:10.1080/14992027.2020.1853262]
13. Gagne JP, Besser J, Lemke U. Behavioral assessment of listening effort using a dual-task paradigm: A review. Trends Hear. 2017; 21:2331216516687287. [DOI:10.1177/2331216516687287]
14. Khalifeh S, Oryan S, Digaleh H, Shaerzadeh F, Khodagholi F, Maghsoudi N, et al. Involvement of Nrf2 in development of anxiety-like behavior by linking Bcl2 to oxidative phosphorylation: Estimation in rat hippocampus, amygdala, and prefrontal cortex. J Mol Neurosci. 2015; 55(2):492-9. [DOI:10.1007/s12031-014-0370-z]
15. Bass JJ, Wilkinson DJ, Rankin D, Phillips BE, Szewczyk NJ, Smith K, et al. An overview of technical considerations for Western blotting applications to physiological research. Scand J Med Sci Sports. 2017; 27(1):4-25. [DOI:10.1111/sms.12702]
16. Nitsche M, Fricke K, Henschke U, Schlitterlau A, Liebetanz D, Lang N, et al. Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans. J Physiol. 2003; 553(Pt 1):293-301. [DOI:10.1113/jphysiol.2003.049916]
17. Nitsche MA, Fricke K, Henschke U, Schlitterlau A, Liebetanz D, Lang N, et al. Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans. J Physiol. 2003; 553(Pt 1):293-301. [DOI:10.1113/jphysiol.2003.049916]
18. Ghanavati E, Salehinejad MA, De Melo L, Nitsche MA, Kuo MF. NMDA receptor-related mechanisms of dopaminergic modulation of tDCS-induced neuroplasticity. Cereb Cortex. 2022; 32(23):5478-88. [DOI:10.1093/cercor/bhac028]
19. Barassi G, Saggini R, Carmignano S, Ancona E, Di felice P, Giannuzzo G, et al. Bilateral Transcranial Direct-current Stimulation (tDCS) of Dorsolateral Prefrontal Cortex during Specific Working Memory Tasks. Int J Phys Med Rehabil. 2016; 4:5. [DOI:10.4172/2329-9096.1000364]
20. Bjekic J, Colic MV, Zivanovic M, Milanovic SD, Filipovic SR. Transcranial direct current stimulation (tDCS) over parietal cortex improves associative memory. Neurobiol Learn Mem. 2019; 157:114-20. [DOI:10.1016/j.nlm.2018.12.007]
21. Chan MMY, Yau SSY, Han YMY. The neurobiology of prefrontal transcranial direct current stimulation (tDCS) in promoting brain plasticity: A systematic review and meta-analyses of human and rodent studies. Neurosci Biobehav Rev. 2021; 125:392-416. [DOI:10.1016/j.neubiorev.2021.02.035]
22. Degeest S, Kestens K, Keppler H. Investigation of the relation between tinnitus, cognition, and the amount of listening effort. J Speech Lang Hear Res. 2022; 65(5):1988-2002. [DOI:10.1044/2022_JSLHR-21-00347]
23. Framorando D, Cai T, Wang Y, Pegna AJ. Effects of Transcranial Direct Current Stimulation on effort during a working-memory task. Sci Rep. 2021; 11(1):16399. [DOI:10.1038/s41598-021-95639-7]
24. Coffman BA, Clark VP, Parasuraman R. Battery powered thought: enhancement of attention, learning, and memory in healthy adults using transcranial direct current stimulation. Neuroimage. 2014; 85 Pt 3:895-908. [DOI:10.1016/j.neuroimage.2013.07.083]
25. Luber B. Neuroenhancement by noninvasive brain stimulation is not a net zero-sum proposition. Front Syst Neurosci. 2014; 8:127. [DOI:10.3389/fnsys.2014.00127]
26. Abellaneda-Perez K, Vaque-Alcazar L, Perellon-Alfonso R, Bargallo N, Kuo MF, Pascual-Leone A, et al. Differential tDCS and tACS effects on working memory-related neural activity and resting-state connectivity. Front Neurosci. 2020; 13:1440. [DOI:10.3389/fnins.2019.01440]
27. Sarkis RA, Kaur N, Camprodon JA. Transcranial direct current stimulation (tDCS): Modulation of executive function in health and disease. Curr Behav Neurosci Rep. 2014; 1:74-85. [DOI:10.1007/s40473-014-0009-y]
28. Santos VSDSD, Zortea M, Alves RL, Naziazeno CCDS, Saldanha JS, Carvalho SDCR, et al. Cognitive effects of transcranial direct current stimulation combined with working memory training in fibromyalgia: A randomized clinical trial. Sci Rep. 2018; 8(1):12477. [DOI:10.1038/s41598-018-30127-z]
29. Luber B, Lisanby SH. Enhancement of human cognitive performance using transcranial magnetic stimulation (TMS). Neuroimage. 2014; 85 Pt 3(0 3):961-70. [DOI:10.1016/j.neuroimage.2013.06.007]
30. Nilsson J, Lebedev AV, Lovden M. No Significant effect of prefrontal tDCS on working memory performance in older adults. Front Aging Neurosci. 2015; 7:230. [DOI:10.3389/fnagi.2015.00230]
31. Friedrich EVC, Berger B, Minarik T, Schmid D, Peylo C, Sauseng P. No enhancing effect of fronto-medial tDCS on working memory processes. J Cogn Enhanc. 2019; 3(4):416-24. [DOI:10.1007/s41465-019-00136-5]
32. Brunoni AR, Vanderhasselt MA. Working memory improvement with non-invasive brain stimulation of the dorsolateral prefrontal cortex: A systematic review and meta-analysis. Brain Cogn. 2014; 86:1-9. [DOI:10.1016/j.bandc.2014.01.008]
33. Degeest S, Keppler H, Corthals P. Listening effort in normal-hearing young adults with chronic tinnitus. J Hear Scie. 2017; 7(2).
2. Andersson G. Tinnitus patients with cognitive problems: Causes and possible treatments. Hear J. 2009; 62(11):27-8. [DOI:10.1097/01.HJ.0000364273.37223.ff]
3. Neff P, Simoes J, Psatha S, Nyamaa A, Boecking B, Rausch L, et al. The impact of tinnitus distress on cognition. Sci Rep. 2021; 11(1):2243. [DOI:10.1038/s41598-021-81728-0]
4. Tai Y, Husain FT. The Role of Cognitive Control in Tinnitus and Its Relation to Speech-in-Noise Performance. J Audiol Otol. 2019; 23(1):1-7. [DOI:10.7874/jao.2018.00409]
5. Rossiter S, Stevens C, Walker G. Tinnitus and its effect on working memory and attention. J Speech Lang Hear Res. 2006; 49(1):150-60. [DOI:10.1044/1092-4388(2006/012)]
6. Martins ML, Souza DDS, Cavalcante MeOB, Barboza HN, de Medeiros JF, Dos Santos Andrade SMM, et al. Effect of transcranial Direct Current Stimulation for tinnitus treatment: A systematic review and meta-analysis. Neurophysiol Clin. 2022; 52(1):1-16. [DOI:10.1016/j.neucli.2021.12.005]
7. Ghanavati E, Salehinejad MA, De Melo L, Nitsche MA, Kuo MF. NMDA receptor-related mechanisms of dopaminergic modulation of tDCS-induced neuroplasticity. Cerebral Cortex. 2022; 32(23):5478-88. [DOI:10.1093/cercor/bhac028]
8. Hoare DJ, Edmondson-Jones M, Gander PE, Hall DA. Agreement and reliability of tinnitus loudness matching and pitch likeness rating. Plos One. 2014; 9(12):e114553. [DOI:10.1371/journal.pone.0114553]
9. Meikle MB, Henry JA, Griest SE, Stewart BJ, Abrams HB, McArdle R, et al. The tinnitus functional index: Development of a new clinical measure for chronic, intrusive tinnitus. Ear Hear. 2012; 33(2):153-76. [DOI:10.1097/AUD.0b013e31822f67c0]
10. Mahdavi ME, Meymeh MH, Nazeri A, Jalilvand H, Heidari F, Fathollahzadeh F. A preliminary study on the reliability of the Persian version of the tinnitus functional index in a military population. Audit Vestib Res. 2020. [DOI:10.18502/avr.v29i2.2794]
11. Torrance GW, Feeny D, Furlong W. Visual analog scales: Do they have a role in the measurement of preferences for health states? Med Decis Making. 2001; 21(4):329-34. [DOI:10.1177/0272989X0102100408]
12. Alhanbali S, Munro KJ, Dawes P, Carolan PJ, Millman RE. Dimensions of self-reported listening effort and fatigue on a digits-in-noise task, and association with baseline pupil size and performance accuracy. Int J Audiol. 2021; 60(10):762-72. [DOI:10.1080/14992027.2020.1853262]
13. Gagne JP, Besser J, Lemke U. Behavioral assessment of listening effort using a dual-task paradigm: A review. Trends Hear. 2017; 21:2331216516687287. [DOI:10.1177/2331216516687287]
14. Khalifeh S, Oryan S, Digaleh H, Shaerzadeh F, Khodagholi F, Maghsoudi N, et al. Involvement of Nrf2 in development of anxiety-like behavior by linking Bcl2 to oxidative phosphorylation: Estimation in rat hippocampus, amygdala, and prefrontal cortex. J Mol Neurosci. 2015; 55(2):492-9. [DOI:10.1007/s12031-014-0370-z]
15. Bass JJ, Wilkinson DJ, Rankin D, Phillips BE, Szewczyk NJ, Smith K, et al. An overview of technical considerations for Western blotting applications to physiological research. Scand J Med Sci Sports. 2017; 27(1):4-25. [DOI:10.1111/sms.12702]
16. Nitsche M, Fricke K, Henschke U, Schlitterlau A, Liebetanz D, Lang N, et al. Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans. J Physiol. 2003; 553(Pt 1):293-301. [DOI:10.1113/jphysiol.2003.049916]
17. Nitsche MA, Fricke K, Henschke U, Schlitterlau A, Liebetanz D, Lang N, et al. Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans. J Physiol. 2003; 553(Pt 1):293-301. [DOI:10.1113/jphysiol.2003.049916]
18. Ghanavati E, Salehinejad MA, De Melo L, Nitsche MA, Kuo MF. NMDA receptor-related mechanisms of dopaminergic modulation of tDCS-induced neuroplasticity. Cereb Cortex. 2022; 32(23):5478-88. [DOI:10.1093/cercor/bhac028]
19. Barassi G, Saggini R, Carmignano S, Ancona E, Di felice P, Giannuzzo G, et al. Bilateral Transcranial Direct-current Stimulation (tDCS) of Dorsolateral Prefrontal Cortex during Specific Working Memory Tasks. Int J Phys Med Rehabil. 2016; 4:5. [DOI:10.4172/2329-9096.1000364]
20. Bjekic J, Colic MV, Zivanovic M, Milanovic SD, Filipovic SR. Transcranial direct current stimulation (tDCS) over parietal cortex improves associative memory. Neurobiol Learn Mem. 2019; 157:114-20. [DOI:10.1016/j.nlm.2018.12.007]
21. Chan MMY, Yau SSY, Han YMY. The neurobiology of prefrontal transcranial direct current stimulation (tDCS) in promoting brain plasticity: A systematic review and meta-analyses of human and rodent studies. Neurosci Biobehav Rev. 2021; 125:392-416. [DOI:10.1016/j.neubiorev.2021.02.035]
22. Degeest S, Kestens K, Keppler H. Investigation of the relation between tinnitus, cognition, and the amount of listening effort. J Speech Lang Hear Res. 2022; 65(5):1988-2002. [DOI:10.1044/2022_JSLHR-21-00347]
23. Framorando D, Cai T, Wang Y, Pegna AJ. Effects of Transcranial Direct Current Stimulation on effort during a working-memory task. Sci Rep. 2021; 11(1):16399. [DOI:10.1038/s41598-021-95639-7]
24. Coffman BA, Clark VP, Parasuraman R. Battery powered thought: enhancement of attention, learning, and memory in healthy adults using transcranial direct current stimulation. Neuroimage. 2014; 85 Pt 3:895-908. [DOI:10.1016/j.neuroimage.2013.07.083]
25. Luber B. Neuroenhancement by noninvasive brain stimulation is not a net zero-sum proposition. Front Syst Neurosci. 2014; 8:127. [DOI:10.3389/fnsys.2014.00127]
26. Abellaneda-Perez K, Vaque-Alcazar L, Perellon-Alfonso R, Bargallo N, Kuo MF, Pascual-Leone A, et al. Differential tDCS and tACS effects on working memory-related neural activity and resting-state connectivity. Front Neurosci. 2020; 13:1440. [DOI:10.3389/fnins.2019.01440]
27. Sarkis RA, Kaur N, Camprodon JA. Transcranial direct current stimulation (tDCS): Modulation of executive function in health and disease. Curr Behav Neurosci Rep. 2014; 1:74-85. [DOI:10.1007/s40473-014-0009-y]
28. Santos VSDSD, Zortea M, Alves RL, Naziazeno CCDS, Saldanha JS, Carvalho SDCR, et al. Cognitive effects of transcranial direct current stimulation combined with working memory training in fibromyalgia: A randomized clinical trial. Sci Rep. 2018; 8(1):12477. [DOI:10.1038/s41598-018-30127-z]
29. Luber B, Lisanby SH. Enhancement of human cognitive performance using transcranial magnetic stimulation (TMS). Neuroimage. 2014; 85 Pt 3(0 3):961-70. [DOI:10.1016/j.neuroimage.2013.06.007]
30. Nilsson J, Lebedev AV, Lovden M. No Significant effect of prefrontal tDCS on working memory performance in older adults. Front Aging Neurosci. 2015; 7:230. [DOI:10.3389/fnagi.2015.00230]
31. Friedrich EVC, Berger B, Minarik T, Schmid D, Peylo C, Sauseng P. No enhancing effect of fronto-medial tDCS on working memory processes. J Cogn Enhanc. 2019; 3(4):416-24. [DOI:10.1007/s41465-019-00136-5]
32. Brunoni AR, Vanderhasselt MA. Working memory improvement with non-invasive brain stimulation of the dorsolateral prefrontal cortex: A systematic review and meta-analysis. Brain Cogn. 2014; 86:1-9. [DOI:10.1016/j.bandc.2014.01.008]
33. Degeest S, Keppler H, Corthals P. Listening effort in normal-hearing young adults with chronic tinnitus. J Hear Scie. 2017; 7(2).
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| Tinnitus transcranial direct current stimulation working memory listening effort N-methyl-D-aspartate receptor 1,2 | ||
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How to Cite
1.
Imani A, Nasehi M, Jalilvand H, Zarrindast M-R, Khalife S. The Impact of Anodal Prefrontal Transcranial Stimulation on Listening Effort, Working Memory and the expression of N-methyl-D-aspartate receptor blood protein in patients with tinnitus. Aud Vestib Res. 2025;.
