Evaluation of the effectiveness of migraine therapy using functional resting MRI with course rhythmic transcranial magnetic stimulation

Introduction. In the context of the search for new migraine therapy options, strict control of their eff ectiveness by means of objective examination methods is required.

Objective. Objective assessment of the eff ectiveness of TMS in patients with migraine on the basis of functional magnetic resonance imaging (fMRI) data.

Material and methods. Resting-state fMRI before and after a fi ve-day course of TMS of the junction of the inferior frontal and temporal lobes bilaterally was performed in 19 patients with migraine. Changes in functional connectivity (FC) of the main neuronal networks of the brain, as well as clinical parameters of pain and quality of life of the patients were assessed before and after the course of TMS.

Results. A decrease in pain intensity and anxiety scores, as well as a decrease in the number of acute pain medications taken, was observed against the background of the therapy. Changes in FC aff ected three main networks: the default mode network, the salience and visual networks. At the same time, decreased effi cacy of therapy was noted in patients with higher severity of depressive symptoms and presence of neuroimaging criteria of depression.

Conclusion. The study suggests the effi cacy of TMS in patients with migraine based on neuroimaging criteria. It is worth paying special attention to the presence of depressive symptoms in migraine patients.

1. Steiner T.J., Stovner L. J., Jensen R., Uluduz D., Katsarava Z. Migraine remains second among the world’s causes of disability, and fi rst among young women: fi ndings from GBD2019. J Headache Pain. 2020;21(1):137. https://doi.org/10.1186/s10194-020-01208-0

2. GBD 2016 Headache Collaborators. Global, regional, and national burden of migraine and tension-type headache, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018;17(11):954–976. https://doi.org/10.1016/S1474-4422(18)30322-3

3. Raff aelli B., Terhart M., Overeem L.H., Mecklenburg J., Neeb L., Steinicke M., Reuter U. Migraine evolution after the cessation of CGRP(-receptor) antibody prophylaxis: a prospective, longitudinal cohort study. Cephalalgia. 2022;42(4–5):326–334. https:// doi.org/10.1177/03331024211046617

4. Schwedt T.J., Vargas B. Neurostimulation for Treatment of Migraine and Cluster Headache. Pain Med. 2015;16(9):1827–1834. https://doi.org/10.1111/pme.12792

5. Barker A.T, Shields K. Transcranial Magnetic Stimulation: Basic Principles and Clinical Applications in Migraine. Headache. 2017;57(3):517–524. https://doi.org/10.1111/head.13002

6. Lan L., Zhang X., Li X., Rong X., Peng Y. The effi cacy of transcranial magnetic stimulation on migraine: a meta-analysis of randomized controlled trails. J Headache Pain. 2017;18(1):86. https://doi.org/10.1186/s10194-017-0792-4

7. Evers S. Non-Invasive Neurostimulation Methods for Acute and Preventive Migraine Treatment-A Narrative Review. J Clin Med. 2021;10(15):3302. https://doi.org/10.3390/jcm10153302

8. Dodick D.W., Schembri C.T., Helmuth M., Aurora S.K. Transcranial magnetic stimulation for migraine: a safety review. Headache. 2010;50(7):1153–1163. https://doi.org/10.1111/j.1526-4610.2010.01697

9. Zhang B., Liu J., Bao T., Wilson G., Park J., Zhao B., Kong J. Locations for noninvasive brain stimulation in treating depressive disorders: A combination of meta-analysis and resting-state functional connectivity analysis. Aust N Z J Psychiatry. 2020;54(6):582– 590. https://doi.org/10.1177/0004867420920372

10. Leung A., Shirvalkar P., Chen R., Kuluva J., Vaninetti M., Bermudes R. et al. Transcranial Magnetic Stimulation for Pain, Headache, and Comorbid Depression: INS-NANS Expert Consensus Panel Review and Recommendation. Neuromodulation. 2020;23(3):267–290. https://doi.org//10.1111/ner.13094

11. Evers S. Non-Invasive Neurostimulation Methods for Acute and Preventive Migraine Treatment-A Narrative Review. J Clin Med. 2021;10(15):3302. https://doi.org/10.3390/jcm10153302

12. Vaninetti M., Lim M., Khalaf A., Metzger-Smith V., Flowers M., Kunnel A., Yang E., et al.fMRI fi ndings in MTBI patients with headaches following rTMS. Sci Rep. 2021;11(1):9573. https://doi.org/10.1038/s41598-021-89118-2

13. Schwedt T.J., Chiang C.C., Chong C.D., Dodick D.W. Functional MRI of migraine. Lancet Neurol. 2015;14(1):81–91. https://doi.org/10.1016/S1474-4422(14)70193-0.

14. Russo A., Silvestro M., Tedeschi G., Tessitore A. Physiopathology of Migraine: What Have We Learned from Functional Imaging? Curr Neurol Neurosci Rep. 2017;17(12):95. https://doi.org/10.1007/s11910-017-0803-5

15. Skorobogatykh K., van Hoogstraten W.S., Degan D., Prischepa A., Savitskaya A., Ileen B.M. et al. Functional connectivity studies in migraine: what have we learned? J Headache Pain. 2019;20(1):108. https://doi.org/10.1186/s10194-019-1047-3

16. Brennan K.C., Pietrobon D. A Systems Neuroscience Approach to Migraine. Neuron. 2018;97(5):1004–1021. https://doi.org/10.1016/j.neuron.2018.01.029

17. Seewoo B.J., Etherington S.J., Feindel K.W., Rodger J. Combined rTMS/fMRI Studies: An Overlooked Resource in Animal Models. Front Neurosci. 2018;12:180. https://doi.org/10.3389/fnins.2018.00180

18. Andreou A.P., Holland P.R., Akerman S., Summ O., Fredrick J., Goadsby P.J. Transcranial magnetic stimulation and potential cortical and trigeminothalamic mechanisms in migraine. Brain. 2016;139(7):2002–2014. https://doi.org/10.1093/brain/aww118

19. Androulakis X.M., Rorden C., Peterlin B.L., Krebs K. Modulation of salience network intranetwork resting state functional connectivity in women with chronic migraine. Cephalalgia. 2018;38(11):1731–1741. https://doi.org/10.1177/0333102417748570

20. Veréb D., Szabó N., Tuka B., Tajti J., Király A., Faragó P. et al. Temporal instability of salience network activity in migraine with aura. Pain. 2020;161(4):856–864. https://doi.org/10.1097/j.pain.0000000000001770

21. He Z., Zhao J., Shen J., Muhlert N., Elliott R., Zhang D. The right VLPFC and downregulation of social pain: A TMS study. Hum Brain Mapp. 2020;41(5):1362–1371. https://doi.org/10.1002/hbm.24881

22. Freedberg M., Reeves J.A., Toader A.C., Hermiller M.S., Kim E., Haubenberger D. et al. Optimizing Hippocampal-Cortical Network Modulation via Repetitive Transcranial Magnetic Stimulation: A Dose-Finding Study Using the Continual Reassessment Method. Neuromodulation. 2020;23(3):366–372. https://doi.org/10.1111/ner.13052

23. Hartwigsen G., Volz L.J. Probing rapid network reorganization of motor and language functions via neuromodulation and neuroimaging. Neuroimage. 2021;224:117449. https://doi.org/10.1016/j.neuroimage.2020.117449

24. Chong C.D., Schwedt T.J., Hougaard A. Brain functional connectivity in headache disorders: A narrative review of MRI investigations. J Cereb Blood Flow Metab. 2019;39(4):650–669. https://doi.org/10.1177/0271678X17740794

25. Headache Classifi cation Committee of the International Headache Society (IHS) The International Classifi cation of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013;33(9):629– 808. https://doi.org/10.1177/0333102413485658

26. Whitfi eld-Gabrieli S., Nieto-Castanon A. Conn: A functional connectivity toolbox for correlated and anticorrelated brain networks. Brain connectivity. 2012;2(3):125–141. https://doi.org/10.1089/brain.2012.0073

27. Calhoun V.D., Adali T., Pearlson G.D., Pekar J.J. A method for making group inferences from functional MRI data using independent component analysis. Hum Brain Mapp. 2001;14(3):140– 151. https://doi.org/10.1002/hbm.1048

28. Worsley K.J., Marrett S., Neelin P., Vandal A.C., Friston K.J., Evans A.C. A unifi ed statistical approach for determining signifi cant signals in images of cerebral activation. Human brain mapping. 1996;4(1):58–73. https://doi.org/10.1002/(SICI)1097-0193(1996)4:1<58::AID-HBM4>3.0.CO;2-O

29. Chabran E., Noblet V., Loureiro de Sousa P., Demuynck C., Philippi N., Mutter C. et al. Changes in gray matter volume and functional connectivity in dementia with Lewy bodies compared to Alzheimer’s disease and normal aging: implications for fl uctuations. Alzheimers Res Ther. 2020;12(1):9. https://doi.org/10.1186/s13195-019-0575-z

30. de Tommaso M., Vecchio E., Quitadamo S.G., Coppola G., Di Renzo A., Parisi V. et al. Pain-Related Brain Connectivity Changes in Migraine: A Narrative Review and Proof of Concept about Possible Novel Treatments Interference. Brain Sci. 2021;11(2):234. https://doi.org/10.3390/brainsci11020234

31. Russo A., Silvestro M., Trojsi F., Bisecco A., De Micco R., Caiazzo G. et al. Cognitive Networks Disarrangement in Patients With Migraine Predicts Cutaneous Allodynia. Headache. 2020;60(7):12281243. https://doi.org/10.1111/head.13860

32. Zhang J., Su J., Wang M., Zhao Y., Yao Q., Zhang Q. et al. Increased default mode network connectivity and increased regional homogeneity in migraineurs without aura. J Headach Pain. 2016;17(1):98. https://doi.org/10.1186/s10194-016-0692-z

33. Tu Y., Zeng F., Lan L., Li Z., Maleki N., Liu B. et al. An fMRI-based neural marker for migraine without aura. Neurology. 2020;94(7):e741–e751. https://doi.org/10.1212/WNL.0000000000008962

34. Hodkinson D.J., Veggeberg R., Kucyi A., van Dijk K.R., Wilcox S.L., Scrivani S.J. et al. Cortico-Cortical Connections of Primary Sensory Areas and Associated Symptoms in Migraine. eNeuro. 2017;3(6):ENEURO.0163-16.2016. https://doi.org/10.1523/ENEURO.0163-16.2016

35. Galambos A., Szabó E., Nagy Z., Édes A.E., Kocsel N., Juhász G., Kökönyei G. A systematic review of structural and functional MRI studies on pain catastrophizing. J Pain. 2019;12:1155– 1178. https://doi.org/10.2147/JPR.S192246

36. Puledda F., Ffytche D., O’Daly O., Goadsby P.J. Imaging the Visual Network in the Migraine Spectrum. Front Neurol. 2019;10:1325. https://doi.org/10.3389/fneur.2019.01325

37. Coppola G., Di Renzo A., Tinelli E., Lepre C., Di Lorenzo C., Di Lorenzo G. et al. Thalamo-cortical network activity between migraine attacks: Insights from MRI-based microstructural and functional resting-state network correlation analysis. J Headache Pain. 2016;17(1):100. https://doi.org/10.1186/s10194-016-0693-y

38. Niddam D.M., Lai K.L., Fuh J.L., Chuang C.Y., Chen W.T., Wang S.J. Reduced functional connectivity between salience and visual networks in migraine with aura. Cephalalgia. 2016;36(1):53–66. https://doi.org/10.1177/0333102415583144

39. Ke J., Yu Y., Zhang X., Su Y., Wang X., Hu S. et al. Functional Alterations in the Posterior Insula and Cerebellum in Migraine Without Aura: A Resting-State MRI Study. Front Behav Neurosci. 2020;14:567588. https://doi.org/10.3389/fnbeh.2020.567588

40. Kumar S., Singh S., Kumar N., Verma R. The Eff ects of Repetitive Transcranial Magnetic Stimulation at Dorsolateral Prefrontal Cortex in the Treatment of Migraine Comorbid with Depression: A Retrospective Open Study. Clin Psychopharmacol Neurosci. 2018;16(1):62–66. https://doi.org/10.9758/cpn.2018.16.1.62