REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION (rTMS) AS A NON-INVASIVE NEUROMODULATION FOR THE SPECTRUM OF NON-MOTOR SYMPTOMS IN PARKINSON’S DISEASE: A SYSTEMATIC REVIEW
DOI:
https://doi.org/10.20961/magnaneurologica.v4i2.3441Keywords:
non-motor symptoms, parkinson’s disease, Repetitive Transcranial Magnetic Stimulation (rTMS)Abstract
Background: Non-motor symptoms are an essential component of Parkinson’s disease (PD) and represent a major contributor to disability and quality of life. Repetitive transcranial magnetic stimulation (rTMS) has been explored as a non-invasive adjunctive therapy; however, evidence remains heterogeneous and limited to specific symptom domains.
Objective: This systematic review aimed to synthesize randomized controlled trial (RCT) evidence on the efficacy and safety of rTMS for non-motor symptoms in PD.
Methods: RCTs published between 2017 and 2026 were identified from PubMed, Nature Portfolio, and SpringerLink. Twelve studies with PD were included, comparing active rTMS with sham. Outcomes encompassed sleep disturbances, depression, anxiety, pain, apathy, constipation, and cognitive impairment. Risk of bias was evaluated using Cochrane RoB 2.0.
Results: Twelve RCTs (566 patients) with PD were included. rTMS showed the most consistent benefits for sleep disturbances and depressive symptoms, particularly with low-frequency stimulation targeting the right dorsolateral prefrontal cortex (DLPFC). Evidence for anxiety, pain, apathy, and cognitive outcomes was moderate and variable, with effects dependent on stimulation parameters and cortical targets; cognitive benefits were largely confined to executive domains. Preliminary evidence suggested a potential emerging role for rTMS in improving constipation via prefrontal modulation of the gut–brain axis. Overall, rTMS was well tolerated, with only mild and transient adverse events reported and no serious safety concerns.
Conclusion: rTMS is a safe and well-tolerated neuromodulation approach with potential domain-specific benefits for non-motor symptoms in PD, particularly sleep and depression. This review contributes to the current understanding of symptom-targeted rTMS applications in PD.
References
1. Wang M, Zhang W, Zang W. Repetitive transcranial magnetic stimulation improves cognition, depression, and walking ability in patients with Parkinson’s disease: a meta-analysis. BMC Neurol; 2024. 24:490. DOI: 10.1186/s12883-024-03960-5
2. Xia Y, Wan H, Hu X, Sun W, Li Y. Effects of different frequencies of repetitive transcranial magnetic stimulation on sleep disorders and depression in patients with Parkinson’s disease: a systematic review and network meta-analysis. Front Aging Neurosci; 2025. DOI: 10.3389/fnagi.2025.1623917
3. Wang Z, Chen S, Zhu Q, Chen S, Zou Y, Chen G, et al. Comparative efficacy of different modalities of transcranial magnetic stimulation for treating Parkinson’s disease with depression: a systematic review and network meta-analysis. Front Neurol; 2025. DOI: 10.3389/fneur.2025.1627932
4. Dan H, Zhiyan S, Chanji W, Huiduan Z, Peijian H. Effect of recurrent TMS and psychological therapy on Parkinson’s patients’ cognitive performance, anxiety, and depressed mood. Rev Psiquiatr Clin; 2023. 50:57–62. DOI: 10.11606/issn.1981-1624.v50i2p57-62
5. Cheng B, Zhu T, Zhao W, Sun L, Shen Y, Xiao W, et al. Effect of Theta Burst Stimulation-Patterned rTMS on Motor and Nonmotor Dysfunction of Parkinson’s Disease: A Systematic Review and Meta-analysis. Front Neurol; 2022. 12:762100. DOI: 10.3389/fneur.2021.762100
6. Yang Y, Yan Z, Chang W, Ding J, Xu H. Effect of different modalities of transcranial magnetic stimulation on Parkinson’s patients cognitive impairment and long-term effectiveness: a systematic review and network meta-analysis. Front Neurosci; 2024. DOI: 10.3389/fnins.2024.1354864
7. Barboza VR, Kubota GT, da Silva VA, et al. Posterior insula repetitive transcranial magnetic stimulation for chronic pain in patients with Parkinson disease – pain type matters: A double-blinded randomized sham-controlled trial. Neurophysiol Clin; 2024. DOI: 10.1016/j.neucli.2024.102994
8. Wu J, Zhuang S, Zhang X, Wang L, Ma X, Jin H, et al. Objective sleep enhancement in Parkinson’s disease: A sham-controlled trial of low-frequency repetitive transcranial magnetic stimulation over the right dorsolateral prefrontal cortex. Parkinsonism Relat Disord; 2024. DOI: 10.1016/j.parkreldis.2024.107050
9. Bo Q, Li Y, Wang X, Wang H, Liu H. Clinical mechanisms of repetitive transcranial magnetic stimulation in improving constipation in Parkinson’s disease patients through the gut-brain axis. Front Aging Neurosci; 2025. DOI: 10.3389/fnagi.2025.1607791
10. Shaheen HA, Gomaa M, Maarouf MM, Daker LI. Exploring the effect of transcranial magnetic stimulation on quality of sleep in Parkinson’s disease. Egypt J Neurol Psychiatry Neurosurg; 2023. 59:171. DOI: 10.1186/s41983-023-00771-y
11. Wei W, Yi X, Ruan J, Duan X, Luo H. The efficacy of repetitive transcranial magnetic stimulation on emotional processing in apathetic patients with Parkinson’s disease: A sham stimulation-controlled ERP study. J Affect Disord; 2021. 282:776–785. DOI: 10.1016/j.jad.2020.12.163
12. Khedr EM, Ahmed GK, Korayem MA, Elamary SASH, El-kholy MM, Haridy NA. Short-Term
13. Therapeutic Effect of Repetitive Transcranial Magnetic Stimulations of Sleep Disorders in Parkinson’s Disease: A Randomized Clinical Trial (Pilot Study). Brain Sci; 2024. 14(6):556. DOI: 10.3390/brainsci14060556
14. Li J, Mi TM, Zhu BF, Ma JH, Han C, Li Y, et al. High-frequency repetitive transcranial magnetic stimulation over the primary motor cortex relieves musculoskeletal pain in patients with Parkinson’s disease: A randomized controlled trial. Parkinsonism Relat Disord; 2020. 80:113–119. DOI: 10.1016/j.parkreldis.2020.10.004
15. Feng Z, Li M, Zheng Y, Ping W, Zhou Z. Efficacy of low-frequency repetitive transcranial magnetic stimulation in the treatment of sleep disorders in the early stage of Parkinson disease: A single-center double-blind controlled study. Medicine (Baltimore); 2025. 104:e44780. DOI: 10.1097/MD.0000000000044780
16. Zhang X, Zhuang S, Wu J, Wang L, Mao C, Chen J, et al. Effects of repetitive transcranial magnetic stimulation over right dorsolateral prefrontal cortex on excessive daytime sleepiness in patients with Parkinson’s disease. Sleep Med; 2022. 100:133–138. DOI: 10.1016/j.sleep.2022.08.021
17. Yokoe M, Mano T, Maruo T, et al. The optimal stimulation site for high-frequency repetitive transcranial magnetic stimulation in Parkinson’s disease: A double-blind crossover pilot study. J Clin Neurosci; 2018. 47:72–78. DOI: 10.1016/j.jocn.2017.09.032
18. Wei W, Yi X, Wu Z, Ruan J, Luo H, Duan X. Acute improvement in the attention network with repetitive transcranial magnetic stimulation in Parkinson’s disease. Disabil Rehabil; 2022. 44:7958–7966. DOI: 10.1080/09638288.2021.1983047
19. Khedr EM, Sayed SS, Abd A, Tony EH, Abd RG, Shakour E. The role of therapeutic repetitive transcranial magnetic stimulation in treatment of sleep disorders in Parkinson’s disease patients; 2020. Retrieved on January 15, 2026. Available from: https://www.researchsquare.com/
20. Peters SK, Dunlop K, Downar J. Cortico-Striatal-Thalamic Loop Circuits of the Salience Network: A Central Pathway in Psychiatric Disease and Treatment. Front Syst Neurosci; 2016. 10:104. DOI: 10.3389/fnsys.2016.00104
21. Lusicic A, Schruers KR, Pallanti S, Castle DJ. Transcranial magnetic stimulation in the treatment of obsessive–compulsive disorder: current perspectives. Neuropsychiatr Dis Treat; 2018. 14:1721–1736. DOI: 10.2147/NDT.S121148
22. Sultana T, Hasan MA, Kang X, Liou-Johnson V, Adamson MM, Razi A. Neural mechanisms of emotional health in traumatic brain injury patients undergoing rTMS treatment. Mol Psychiatry; 2023. 28:5150–5158. DOI: 10.1038/s41380-023-02289-0
23. Voineskos D, Blumberger DM, Rogasch NC, Zomorrodi R, Farzan F, Foussias G, et al. Neurophysiological effects of repetitive transcranial magnetic stimulation (rTMS) in treatment resistant depression. Clin Neurophysiol; 2021. 132:2306–2316. DOI: 10.1016/j.clinph.2021.05.017
24. Ge R, Humaira A, Gregory E, Alamian G, MacMillan EL, Barlow L, et al. Predictive Value of Acute Neuroplastic Response to rTMS in Treatment Outcome in Depression: A Concurrent TMS-fMRI Trial. Am J Psychiatry; 2022. 179:500–508. DOI: 10.1176/appi.ajp.20220107
25. Fitzsimmons SMDD, Oostra E, Postma TS, van der Werf YD, van den Heuvel OA. Repetitive Transcranial Magnetic Stimulation–Induced Neuroplasticity and the Treatment of Psychiatric Disorders: State of the Evidence and Future Opportunities. Biol Psychiatry; 2024. 95:592–600. DOI: 10.1016/j.biopsych.2023.09.019
26. Rukavina K, Staunton J, Zinzalias P, Skoric MK, Poplawska-Domaszewicz K, Pisani A, et al. Pain in Parkinson’s disease is impacted by motor complications, anxiety and sleep disturbances. Eur J Pain; 2025. DOI: 10.1002/ejp.4765
27. Lei J, Tang LL, You HJ. Pathological pain: Non-motor manifestations in Parkinson disease and its treatment. Neurosci Biobehav Rev; 2024. 161:105646. DOI: 10.1016/j.neubiorev.2024.105646
28. De Andrade DC, Mylius V, Perez-Lloret S, et al. Pain in Parkinson disease: mechanistic substrates, main classification systems, and how to make sense out of them. Pain; 2023. 164:2425–2434. DOI: 10.1097/j.pain.0000000000002923
29. Lefaucheur JP, Aleman A, Baeken C, et al. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014–2018). Clin Neurophysiol; 2020. 131:474–528. DOI: 10.1016/j.clinph.2019.11.002
30. Wiech K. Deconstructing the sensation of pain: The influence of cognitive processes on pain perception. Science; 2016. 354:584–587. DOI: 10.1126/science.aaf8934
31. French IT, Muthusamy KA. A Review of Sleep and Its Disorders in Patients with Parkinson’s Disease in Relation to Various Brain Structures. Front Aging Neurosci; 2016. 8:114. DOI: 10.3389/fnagi.2016.00114
32. Valero-Cabré A, Amengual JL, Stengel C, Pascual-Leone A, Coubard OA. Transcranial magnetic stimulation in basic and clinical neuroscience: A comprehensive review of fundamental principles and novel insights. Neurosci Biobehav Rev; 2017. 83:381–404. DOI: 10.1016/j.neubiorev.2017.10.006
33. Polanía R, Nitsche MA, Ruff CC. Studying and modifying brain function with non-invasive brain stimulation. Nat Neurosci; 2018. 21:174–187. DOI: 10.1038/s41593-017-0054-4
34. Lanza G, Cantone M, Aricò D, et al. Clinical and electrophysiological impact of repetitive low-frequency transcranial magnetic stimulation on the sensory–motor network in patients with restless legs syndrome. Ther Adv Neurol Disord; 2018. 11:1756286418759973. DOI: 10.1177/1756286418759973
35. Cristini J, Medina-Rincon A, Van Roy A, Seo F, Moncion K, Carrier J, et al. Non-invasive brain stimulation to enhance sleep quality and architecture in Parkinson’s disease: A systematic review and Bayesian network meta-analysis. Sleep Med Rev; 2025. 82:102117. DOI: 10.1016/j.smrv.2025.102117
36. Croarkin PE, Elmaadawi AZ, Aaronson ST, Schrodt GR, Holbert RC, Verdoliva S, et al. Left prefrontal transcranial magnetic stimulation for treatment-resistant depression in adolescents: a double-blind, randomized, sham-controlled trial. Neuropsychopharmacology; 2021. 46:462–469. DOI: 10.1038/s41386-020-00829-y
37. Guo B, Zhang M, Hao W, Wang Y, Zhang T, Liu C. Neuroinflammation mechanisms of neuromodulation therapies for anxiety and depression. Transl Psychiatry; 2023. 13:5. DOI: 10.1038/s41398-022-02292-1
38. Tao Y, Liang Q, Zhang F, Guo S, Fan L, Zhao F. Efficacy of non-invasive brain stimulation combined with antidepressant medications for depression: a systematic review and meta-analysis of randomized controlled trials. Syst Rev; 2024. 13:92. DOI: 10.1186/s13643-024-02484-9
39. Brys M, Fox MD, Agarwal S, et al. Multifocal repetitive TMS for motor and mood symptoms of Parkinson disease. Neurology; 2016. 87:1907–1915. DOI: 10.1212/WNL.0000000000003282
40. Komaitis S, Kalyvas AV, Skandalakis GP, et al. The frontal longitudinal system as revealed through the fiber microdissection technique: structural evidence underpinning the direct connectivity of the prefrontal-premotor circuitry. J Neurosurg; 2020. 133:1503–1515. DOI: 10.3171/2019.7.JNS191204
41. Cammisuli D, Ceravolo R, Bonuccelli U. Non-pharmacological interventions for Parkinson’s disease mild cognitive impairment: future directions for research. Neural Regen Res; 2020. 15:1650–1651. DOI: 10.4103/1673-5374.276332
42. Chong TTJ, Husain M. The role of dopamine in the pathophysiology and treatment of apathy. Prog Brain Res; 2016. 229:389–426. DOI: 10.1016/bs.pbr.2016.05.007
43. Le Heron C, Apps MAJ, Husain M. The anatomy of apathy: A neurocognitive framework for amotivated behaviour. Neuropsychologia; 2018. 118:54–67. DOI: 10.1016/j.neuropsychologia.2017.07.003
44. Prange S, Klinger H, Laurencin C, Danaila T, Thobois S. Depression in Patients with Parkinson’s Disease: Current Understanding of its Neurobiology and Implications for Treatment. Drugs Aging; 2022. 39:417–439. DOI: 10.1007/s40266-022-00936-1
45. Biundo R, Weis L, Antonini A. Cognitive decline in Parkinson’s disease: the complex picture. NPJ Parkinsons Dis; 2016. 2:16018. DOI: 10.1038/npjparkd.2016.18
46. Aarsland D, Creese B, Politis M, Chaudhuri KR, ffytche DH, Weintraub D, et al. Cognitive decline in Parkinson disease. Nat Rev Neurol; 2017. 13:217–231. DOI: 10.1038/nrneurol.2017.27
47. Menozzi E, Macnaughtan J, Schapira AHV. The gut-brain axis and Parkinson disease: clinical and pathogenetic relevance. Ann Med; 2021. 53:611–625. DOI: 10.1080/07853890.2021.1900972
48. Moustafa SA, Mohamed S, Dawood A, Azar J, Elmorsy E, Rizk NAM, et al. Gut brain axis: an insight into microbiota role in Parkinson’s disease. Metab Brain Dis; 2021. 36:1545–1557. DOI: 10.1007/s11011-021-00775-7
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