Tracking tDCS induced grey matter changes in episodic migraine: a randomized controlled trial

Simon Schading, Heiko Pohl, Andreas Gantenbein, Roger Luechinger, Peter Sandor, Franz Riederer, Patrick Freund, Lars Michels, Simon Schading, Heiko Pohl, Andreas Gantenbein, Roger Luechinger, Peter Sandor, Franz Riederer, Patrick Freund, Lars Michels

Abstract

Background: Occipital transcranial direct current stimulation (tDCS) is an effective and safe treatment for migraine attack prevention. Structural brain alterations have been found in migraineurs in regions related to pain modulation and perception, including occipital areas. However, whether these structural alterations can be dynamically modulated through tDCS treatment is understudied.

Objective: To track longitudinally grey matter volume changes in occipital areas in episodic migraineurs during and up to five months after occipital tDCS treatment in a single-blind, and sham-controlled study.

Methods: 24 episodic migraineurs were randomized to either receive verum or sham occipital tDCS treatment for 28 days. To investigate dynamic grey matter volume changes patients underwent structural MRI at baseline (prior to treatment), 1.5 months and 5.5 months (after completion of treatment). 31 healthy controls were scanned with the same MRI protocol. Morphometry measures assessed rate of changes over time and between groups by means of tensor-based morphometry.

Results: Before treatment, migraineurs reported 5.6 monthly migraine days on average. A cross-sectional analysis revealed grey matter volume increases in the left lingual gyrus in migraineurs compared to controls. Four weeks of tDCS application led to a reduction of 1.9 migraine days/month and was paralleled by grey matter volume decreases in the left lingual gyrus in the treatment group; its extent overlapping with that seen at baseline.

Conclusion: This study shows that migraineurs have increased grey matter volume in the lingual gyrus, which can be modified by tDCS. Tracking structural plasticity in migraineurs provides a potential neuroimaging biomarker for treatment monitoring.

Trial registration: ClinicalTrials.gov , NCT03237754 . Registered 03 August 2017 - retrospectively registered, https://ichgcp.net/clinical-trials-registry/NCT03237754 .

Keywords: Brain plasticity; Migraine; Structural MRI; Structural alterations; Transcranial direct current stimulation; Voxel-based morphometry.

Conflict of interest statement

Pohl received speaker fees from TEVA Pharmaceuticals and honoraria from Eli Lilly. Franz Riederer has received speaker honoraria from Burgerstein Foundation, Lilly, Teva, and Novartis. Dr. Sandor reports personal fees from Novartis, Teva, Lilly, Almirall, outside the submitted work. Simon Schading, Dr. Gantenbein, Dr. Luechinger, Dr. Freund, and Dr. Michels have no conflicts of interest to disclose.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Overview of the study design. The observation period was subdivided into six 28-day periods (Baseline, T1–5). The tDCS treatment was performed during T1 and was initiated immediately after the baseline visit. FUP1 was scheduled shortly after the end of the stimulation period and FUP2 after T5. Modified from Pohl et al. [32]
Fig. 2
Fig. 2
Significant volumetric differences between migraine patients and healthy controls at baseline. Overlay of statistical parametric maps (uncorrected p < 0.001) shows increased cortical volume in patients versus controls in the left lingual gyrus. The color bar indicates the t-score
Fig. 3
Fig. 3
Significant quadratic differences between verum and sham tDCS group revealed by TBM. Overlay of statistical parametric maps (uncorrected p A). The color bar indicates the t-score. Comparison of the statistical parametric maps (uncorrected p < 0.005, for illustrative purposes) of the cross-sectional cluster (in yellow) and the longitudinal cluster (in red) reveals that the regions of both clusters in the left lingual gyrus overlap (B)
Fig. 4
Fig. 4
Clinical and structural changes following tDCS treatment. Change in monthly migraine days depicted as difference in days between verum and sham tDCS group (A). Change in GM volume depicted as difference in percent between verum and sham tDCS group (B). Negative values represent less migraine days, respectively lower GM volume in the verum tDCS group compared to the sham tDCS group. All values are normalized to the baseline measurement

References

    1. Burch RC, Buse DC, Lipton RB. Migraine: epidemiology, burden, and comorbidity. Neurol Clin. 2019;37(4):631–649. doi: 10.1016/j.ncl.2019.06.001.
    1. GBD Headache collaborators (2018) 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. 2016;17(11):954–976. doi: 10.1016/s1474-4422(18)30322-3.
    1. Abu Bakar N, Tanprawate S, Lambru G, Torkamani M, Jahanshahi M, Matharu M. Quality of life in primary headache disorders: a review. Cephalalgia. 2016;36(1):67–91. doi: 10.1177/0333102415580099.
    1. Buse D, Manack A, Serrano D, Reed M, Varon S, Turkel C, Lipton R. Headache impact of chronic and episodic migraine: results from the American Migraine Prevalence and Prevention study. Headache. 2012;52(1):3–17. doi: 10.1111/j.1526-4610.2011.02046.x.
    1. Blumenfeld AM, Varon SF, Wilcox TK, Buse DC, Kawata AK, Manack A, Goadsby PJ, Lipton RB. Disability, HRQoL and resource use among chronic and episodic migraineurs: results from the international burden of migraine study (IBMS) Cephalalgia. 2011;31(3):301–315. doi: 10.1177/0333102410381145.
    1. Scher AI, Bigal ME, Lipton RB. Comorbidity of migraine. Curr Opin Neurol. 2005;18(3):305–310. doi: 10.1097/01.wco.0000169750.52406.a2.
    1. Minen MT, Begasse De Dhaem O, Kroon Van Diest A, Powers S, Schwedt TJ, Lipton R, Silbersweig D. Migraine and its psychiatric comorbidities. J Neurol Neurosurg Psychiatry. 2016;87(7):741–749. doi: 10.1136/jnnp-2015-312233.
    1. Baigi K, Stewart WF. Headache and migraine: a leading cause of absenteeism. Handb Clin Neurol. 2015;131:447–463. doi: 10.1016/b978-0-444-62627-1.00025-1.
    1. Vargas BB (2018) Acute treatment of migraine. Continuum (Minneap Minn) 24 (4, headache):1032-1051. 24(4):1032–1051. 10.1212/con.0000000000000639
    1. Schwedt TJ. Preventive therapy of migraine. Continuum (Minneap Minn) 2018;24(4):1052–1065. doi: 10.1212/con.0000000000000635.
    1. Viganò A, D'Elia TS, Sava SL, Auvé M, De Pasqua V, Colosimo A, Di Piero V, Schoenen J, Magis D. Transcranial direct current stimulation (tDCS) of the visual cortex: a proof-of-concept study based on interictal electrophysiological abnormalities in migraine. J Headache Pain. 2013;14(1):23. doi: 10.1186/1129-2377-14-23.
    1. Rocha S, Melo L, Boudoux C, Foerster Á, Araújo D, Monte-Silva K. Transcranial direct current stimulation in the prophylactic treatment of migraine based on interictal visual cortex excitability abnormalities: a pilot randomized controlled trial. J Neurol Sci. 2015;349(1–2):33–39. doi: 10.1016/j.jns.2014.12.018.
    1. Antal A, Kriener N, Lang N, Boros K, Paulus W. Cathodal transcranial direct current stimulation of the visual cortex in the prophylactic treatment of migraine. Cephalalgia. 2011;31(7):820–828. doi: 10.1177/0333102411399349.
    1. Ahdab R, Mansour AG, Khazen G, El-Khoury C, Sabbouh TM, Salem M, Yamak W, Ayache SS, Riachi N (2019) Cathodal transcranial direct current stimulation of the occipital cortex in episodic migraine: a randomized sham-controlled crossover study. J Clin Med 9(1). 10.3390/jcm9010060
    1. Dasilva AF, Mendonca ME, Zaghi S, Lopes M, Dossantos MF, Spierings EL, Bajwa Z, Datta A, Bikson M, Fregni F. tDCS-induced analgesia and electrical fields in pain-related neural networks in chronic migraine. Headache. 2012;52(8):1283–1295. doi: 10.1111/j.1526-4610.2012.02141.x.
    1. Andrade SM, de Brito Aranha REL, de Oliveira EA, de Mendonça C, Martins WKN, Alves NT, Fernández-Calvo B. Transcranial direct current stimulation over the primary motor vs prefrontal cortex in refractory chronic migraine: a pilot randomized controlled trial. J Neurol Sci. 2017;378:225–232. doi: 10.1016/j.jns.2017.05.007.
    1. Chase HW, Boudewyn MA, Carter CS, Phillips ML. Transcranial direct current stimulation: a roadmap for research, from mechanism of action to clinical implementation. Mol Psychiatry. 2020;25(2):397–407. doi: 10.1038/s41380-019-0499-9.
    1. Bindman LJ, Lippold OC, Redfearn JW. The action of brief polarizing currents on the cerebral cortex of the rat (1) during current flow and (2) in the production of LONG-lasting after-effects. J Physiol. 1964;172(3):369–382. doi: 10.1113/jphysiol.1964.sp007425.
    1. Antal A, Nitsche MA, Paulus W. Transcranial direct current stimulation and the visual cortex. Brain Res Bull. 2006;68(6):459–463. doi: 10.1016/j.brainresbull.2005.10.006.
    1. Antal A, Kincses TZ, Nitsche MA, Bartfai O, Paulus W. Excitability changes induced in the human primary visual cortex by transcranial direct current stimulation: direct electrophysiological evidence. Invest Ophthalmol Vis Sci. 2004;45(2):702–707. doi: 10.1167/iovs.03-0688.
    1. Nitsche MA, Paulus W. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol 527 Pt. 2000;3(Pt 3):633–639. doi: 10.1111/j.1469-7793.2000.t01-1-00633.x.
    1. Bohotin V, Fumal A, Vandenheede M, Bohotin C, Schoenen J. Excitability of visual V1-V2 and motor cortices to single transcranial magnetic stimuli in migraine: a reappraisal using a figure-of-eight coil. Cephalalgia. 2003;23(4):264–270. doi: 10.1046/j.1468-2982.2003.00475.x.
    1. Mulleners WM, Chronicle EP, Palmer JE, Koehler PJ, Vredeveld JW. Visual cortex excitability in migraine with and without aura. Headache. 2001;41(6):565–572. doi: 10.1046/j.1526-4610.2001.041006565.x.
    1. Coppola G, Schoenen J. Cortical excitability in chronic migraine. Curr Pain Headache Rep. 2012;16(1):93–100. doi: 10.1007/s11916-011-0231-1.
    1. Coppola G, Pierelli F, Schoenen J. Is the cerebral cortex hyperexcitable or hyperresponsive in migraine? Cephalalgia. 2007;27(12):1427–1439. doi: 10.1111/j.1468-2982.2007.01500.x.
    1. Chen WT, Wang SJ, Fuh JL, Lin CP, Ko YC, Lin YY. Persistent ictal-like visual cortical excitability in chronic migraine. Pain. 2011;152(2):254–258. doi: 10.1016/j.pain.2010.08.047.
    1. Chong CD, Schwedt TJ, Dodick DW. Migraine: what imaging reveals. Curr Neurol Neurosci Rep. 2016;16(7):64. doi: 10.1007/s11910-016-0662-5.
    1. Messina R, Rocca MA, Colombo B, Pagani E, Falini A, Goadsby PJ, Filippi M. Gray matter volume modifications in migraine: a cross-sectional and longitudinal study. Neurology. 2018;91(3):e280–e292. doi: 10.1212/wnl.0000000000005819.
    1. Liu J, Lan L, Li G, Yan X, Nan J, Xiong S, Yin Q, von Deneen KM, Gong Q, Liang F, Qin W, Tian J. Migraine-related gray matter and white matter changes at a 1-year follow-up evaluation. J Pain. 2013;14(12):1703–1708. doi: 10.1016/j.jpain.2013.08.013.
    1. Newman-Norlund RD, Rorden C, Maleki N, Patel M, Cheng B, Androulakis XM. Cortical and subcortical changes following sphenopalatine ganglion blocks in chronic migraine with medication overuse headache: a preliminary longitudinal study. Womens Midlife Health. 2020;6(1):7. doi: 10.1186/s40695-020-00055-y.
    1. Headache Classification Committee of the International Headache Society (IHS) (2018) The International Classification of Headache Disorders, 3rd edition. Cephalalgia 38(1):1–211. 10.1177/0333102417738202
    1. Pohl H, Moisa M, Jung HH, Brenner K, Aschmann J, Riederer F, Ruff CC, Schoenen J, Luechinger R, Widmer L, Petersen JA, Gantenbein AR, Sandor PS, Michels L. Long-term effects of self-administered transcranial direct current stimulation in episodic migraine prevention: results of a randomized controlled trial. Neuromodulation. 2020;24(5):890–898. doi: 10.1111/ner.13292.
    1. Ashburner J, Friston KJ. Voxel-based morphometry--the methods. Neuroimage. 2000;11(6 Pt 1):805–821. doi: 10.1006/nimg.2000.0582.
    1. Ashburner J, Friston KJ. Unified segmentation. Neuroimage. 2005;26(3):839–851. doi: 10.1016/j.neuroimage.2005.02.018.
    1. Ashburner J. A fast diffeomorphic image registration algorithm. Neuroimage. 2007;38(1):95–113. doi: 10.1016/j.neuroimage.2007.07.007.
    1. Guillaume B, Hua X, Thompson PM, Waldorp L, Nichols TE. Fast and accurate modelling of longitudinal and repeated measures neuroimaging data. Neuroimage. 2014;94:287–302. doi: 10.1016/j.neuroimage.2014.03.029.
    1. Shajahan PM, Glabus MF, Gooding PA, Shah PJ, Ebmeier KP. Reduced cortical excitability in depression. Impaired post-exercise motor facilitation with transcranial magnetic stimulation. Br J Psychiatry. 1999;174(5):449–454. doi: 10.1192/bjp.174.5.449.
    1. Croarkin PE, Nakonezny PA, Lewis CP, Zaccariello MJ, Huxsahl JE, Husain MM, Kennard BD, Emslie GJ, Daskalakis ZJ. Developmental aspects of cortical excitability and inhibition in depressed and healthy youth: an exploratory study. Front Hum Neurosci. 2014;8:669. doi: 10.3389/fnhum.2014.00669.
    1. Concerto C, Lanza G, Cantone M, Pennisi M, Giordano D, Spampinato C, Ricceri R, Pennisi G, Aguglia E, Bella R. Different patterns of cortical excitability in major depression and vascular depression: a transcranial magnetic stimulation study. BMC Psychiatry. 2013;13(1):300. doi: 10.1186/1471-244x-13-300.
    1. Salustri C, Tecchio F, Zappasodi F, Bevacqua G, Fontana M, Ercolani M, Milazzo D, Squitti R, Rossini PM. Cortical excitability and rest activity properties in patients with depression. J Psychiatry Neurosci. 2007;32(4):259–266.
    1. Gaist D, Hougaard A, Garde E, Reislev NL, Wiwie R, Iversen P, Madsen CG, Blaabjerg M, Nielsen HH, Krøigård T, Østergaard K, Kyvik KO, Hjelmborg J, Madsen K, Siebner HR, Ashina M. Migraine with visual aura associated with thicker visual cortex. Brain. 2018;141(3):776–785. doi: 10.1093/brain/awx382.
    1. Palm-Meinders IH, Arkink EB, Koppen H, Amlal S, Terwindt GM, Launer LJ, van Buchem MA, Ferrari MD, Kruit MC. Volumetric brain changes in migraineurs from the general population. Neurology. 2017;89(20):2066–2074. doi: 10.1212/wnl.0000000000004640.
    1. Granziera C, DaSilva AF, Snyder J, Tuch DS, Hadjikhani N. Anatomical alterations of the visual motion processing network in migraine with and without aura. PLoS Med. 2006;3(10):e402. doi: 10.1371/journal.pmed.0030402.
    1. Messina R, Rocca MA, Colombo B, Valsasina P, Horsfield MA, Copetti M, Falini A, Comi G, Filippi M. Cortical abnormalities in patients with migraine: a surface-based analysis. Radiology. 2013;268(1):170–180. doi: 10.1148/radiol.13122004.
    1. Magon S, May A, Stankewitz A, Goadsby PJ, Schankin C, Ashina M, Amin FM, Seifert CL, Mallar Chakravarty M, Müller J, Sprenger T. Cortical abnormalities in episodic migraine: a multi-center 3T MRI study. Cephalalgia. 2019;39(5):665–673. doi: 10.1177/0333102418795163.
    1. Bonanno L, Lo Buono V, De Salvo S, Ruvolo C, Torre V, Bramanti P, Marino S, Corallo F. Brain morphologic abnormalities in migraine patients: an observational study. J Headache Pain. 2020;21(1):39. doi: 10.1186/s10194-020-01109-2.
    1. Jin C, Yuan K, Zhao L, Zhao L, Yu D, von Deneen KM, Zhang M, Qin W, Sun W, Tian J. Structural and functional abnormalities in migraine patients without aura. NMR Biomed. 2013;26(1):58–64. doi: 10.1002/nbm.2819.
    1. Matharu MS, Good CD, May A, Bahra A, Goadsby PJ. No change in the structure of the brain in migraine: a voxel-based morphometric study. Eur J Neurol. 2003;10(1):53–57. doi: 10.1046/j.1468-1331.2003.00510.x.
    1. Mehnert J, Schulte L, May A. No grey matter alterations in longitudinal data of migraine patients. Brain. 2020;143(11):e93. doi: 10.1093/brain/awaa300.
    1. Sheng L, Zhao P, Ma H, Yuan C, Zhong J, Dai Z, Pan P. A lack of consistent brain grey matter alterations in migraine. Brain. 2020;143(6):e45. doi: 10.1093/brain/awaa123.
    1. Wang HZ, Wang WH, Shi HC, Yuan CH. Is there a reliable brain morphological signature for migraine? J Headache Pain. 2020;21(1):89. doi: 10.1186/s10194-020-01158-7.
    1. Datta R, Detre JA, Aguirre GK, Cucchiara B. Absence of changes in cortical thickness in patients with migraine. Cephalalgia. 2011;31(14):1452–1458. doi: 10.1177/0333102411421025.
    1. Hutton C, Draganski B, Ashburner J, Weiskopf N. A comparison between voxel-based cortical thickness and voxel-based morphometry in normal aging. Neuroimage. 2009;48(2):371–380. doi: 10.1016/j.neuroimage.2009.06.043.
    1. Valfrè W, Rainero I, Bergui M, Pinessi L. Voxel-based morphometry reveals gray matter abnormalities in migraine. Headache. 2008;48(1):109–117. doi: 10.1111/j.1526-4610.2007.00723.x.
    1. Planchuelo-Gómez Á, García-Azorín D, Guerrero ÁL, Rodríguez M, Aja-Fernández S, de Luis-García R. Gray matter structural alterations in chronic and episodic migraine: a morphometric magnetic resonance imaging study. Pain Med. 2020;21(11):2997–3011. doi: 10.1093/pm/pnaa271.
    1. Coppola G, Tinelli E, Lepre C, Iacovelli E, Di Lorenzo C, Di Lorenzo G, Serrao M, Pauri F, Fiermonte G, Bianco F, Pierelli F. Dynamic changes in thalamic microstructure of migraine without aura patients: a diffusion tensor magnetic resonance imaging study. Eur J Neurol. 2014;21(2):287–e213. doi: 10.1111/ene.12296.
    1. Coppola G, Di Renzo A, Tinelli E, Iacovelli E, Lepre C, Di Lorenzo C, Di Lorenzo G, Di Lenola D, Parisi V, Serrao M, Pauri F, Fiermonte G, Bianco F, Pierelli F. Evidence for brain morphometric changes during the migraine cycle: a magnetic resonance-based morphometry study. Cephalalgia. 2015;35(9):783–791. doi: 10.1177/0333102414559732.
    1. Hougaard A, Amin FM, Hoffmann MB, Larsson HB, Magon S, Sprenger T, Ashina M. Structural gray matter abnormalities in migraine relate to headache lateralization, but not aura. Cephalalgia. 2015;35(1):3–9. doi: 10.1177/0333102414532378.
    1. Chong CD, Starling AJ, Schwedt TJ. Interictal photosensitivity associates with altered brain structure in patients with episodic migraine. Cephalalgia. 2016;36(6):526–533. doi: 10.1177/0333102415606080.
    1. Schmitz N, Admiraal-Behloul F, Arkink EB, Kruit MC, Schoonman GG, Ferrari MD, van Buchem MA. Attack frequency and disease duration as indicators for brain damage in migraine. Headache. 2008;48(7):1044–1055. doi: 10.1111/j.1526-4610.2008.01133.x.
    1. Puledda F, Ffytche D, O'Daly O, Goadsby PJ. Imaging the visual network in the migraine Spectrum. Front Neurol. 2019;10:1325. doi: 10.3389/fneur.2019.01325.
    1. Schwedt TJ, Chiang CC, Chong CD, Dodick DW. Functional MRI of migraine. Lancet Neurol. 2015;14(1):81–91. doi: 10.1016/s1474-4422(14)70193-0.
    1. Michels L, Villanueva J, O'Gorman R, Muthuraman M, Koirala N, Büchler R, Gantenbein AR, Sandor PS, Luechinger R, Kollias S, Riederer F. Interictal Hyperperfusion in the higher visual cortex in patients with episodic migraine. Headache. 2019;59(10):1808–1820. doi: 10.1111/head.13646.
    1. Lo Buono V, Bonanno L, Corallo F, Pisani LR, Lo Presti R, Grugno R, Di Lorenzo G, Bramanti P, Marino S. Functional connectivity and cognitive impairment in migraine with and without aura. J Headache Pain. 2017;18(1):72. doi: 10.1186/s10194-017-0782-6.
    1. Li Z, Zhou J, Lan L, Cheng S, Sun R, Gong Q, Wintermark M, Zeng F, Liang F. Concurrent brain structural and functional alterations in patients with migraine without aura: an fMRI study. J Headache Pain. 2020;21(1):141. doi: 10.1186/s10194-020-01203-5.
    1. Tedeschi G, Russo A, Conte F, Corbo D, Caiazzo G, Giordano A, Conforti R, Esposito F, Tessitore A. Increased interictal visual network connectivity in patients with migraine with aura. Cephalalgia. 2016;36(2):139–147. doi: 10.1177/0333102415584360.
    1. Hadjikhani N, Sanchez Del Rio M, Wu O, Schwartz D, Bakker D, Fischl B, Kwong KK, Cutrer FM, Rosen BR, Tootell RB, Sorensen AG, Moskowitz MA. Mechanisms of migraine aura revealed by functional MRI in human visual cortex. Proc Natl Acad Sci U S A. 2001;98(8):4687–4692. doi: 10.1073/pnas.071582498.
    1. Chen SP, Ayata C. Spreading depression in primary and secondary headache disorders. Curr Pain Headache Rep. 2016;20(7):44. doi: 10.1007/s11916-016-0574-8.
    1. Noseda R, Burstein R. Migraine pathophysiology: anatomy of the trigeminovascular pathway and associated neurological symptoms, CSD, sensitization and modulation of pain. Pain. 2013;154(Suppl 1):S44–S53. doi: 10.1016/j.pain.2013.07.021.
    1. Masson R, Demarquay G, Meunier D, Lévêque Y, Hannoun S, Bidet-Caulet A, Caclin A. Is migraine associated to brain anatomical alterations? New data and coordinate-based Meta-analysis. Brain Topogr. 2021;34(3):384–401. doi: 10.1007/s10548-021-00824-6.

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj