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The Journal of Headache and Pain

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Open Access 01-12-2019 | Migraine | Research article

Increased connectivity of pain matrix in chronic migraine: a resting-state functional MRI study

Authors: Mi Ji Lee, Bo-yong Park, Soohyun Cho, Sung Tae Kim, Hyunjin Park, Chin-Sang Chung

Published in: The Journal of Headache and Pain | Issue 1/2019

Abstract

Objective

To investigate the whole-brain resting-state functional connectivity in patients with chronic migraine (CM) using a data-driven method.

Methods

We prospectively recruited patients with either episodic migraine (EM) or CM aged 18–60 years who visited the headache clinic of the Samsung Medical Center from July 2016 to December 2017. All patients underwent 3 T MRI using an identical scanner. Patients were considered interictal if they did not have a migraine headache at the day and ± 1 days of functional MRI acquisition. Using the group-independent component analysis (ICA), connectivity analysis with a weighted and undirected network model was performed. The between-group differences in degree centrality (DC) values were assessed using 5000 permutation tests corrected with false discovery rate (FDR).

Results

A total of 62 patients (44 EM and 18 CM) were enrolled in this study. Among the seven functionally interpretable spatially independent components (ICs) identified, only one IC, interpreted as the pain matrix, showed a significant between-group difference in DC (CM > EM, p = 0.046). This association remained significant after adjustment for age, sex, migraine with aura (MWA), allodynia, depression, and anxiety (p = 0.038). The pain matrix was functionally correlated with the hypothalamus (p = 0.040, EM > CM) and dorsal raphe nucleus (p = 0.039, CM > EM) with different levels of strength in EM and CM.

Conclusion

CM patients have a stronger connectivity in the pain matrix than do EM patients. Functional alteration of the pain network might play a role in migraine chronification.

Headache Classification Committee of the International Headache Society (IHS) (2018) The international classification of headache disorders, 3rd edition. Cephalalgia 38:1–211

Natoli JL, Manack A, Dean B, Butler Q, Turkel CC, Stovner L et al (2010) Global prevalence of chronic migraine: a systematic review. Cephalalgia 30:599–609CrossRef

Lanteri-Minet M, Duru G, Mudge M, Cottrell S (2011) Quality of life impairment, disability and economic burden associated with chronic daily headache, focusing on chronic migraine with or without medication overuse: a systematic review. Cephalalgia 31:837–850CrossRef

Scher AI, Stewart WF, Ricci JA, Lipton RB (2003) Factors associated with the onset and remission of chronic daily headache in a population-based study. Pain 106:81–89CrossRef

Scher AI, Stewart WF, Lipton RB (2004) Caffeine as a risk factor for chronic daily headache: a population-based study. Neurology 63:2022–2027CrossRef

Schulte LH, Allers A, May A (2017) Hypothalamus as a mediator of chronic migraine: evidence from high-resolution fMRI. Neurology 88:2011–2016CrossRef

Schulte LH, Allers A, May A (2018) Visual stimulation leads to activation of the nociceptive trigeminal nucleus in chronic migraine. Neurology 90:e1973–e1978CrossRef

Schwedt TJ, Schlaggar BL, Mar S, Nolan T, Coalson RS, Nardos B et al (2013) Atypical resting-state functional connectivity of affective pain regions in chronic migraine. Headache 53:737–751CrossRef

Headache Classification Committee of the International Headache S (2013) The international classification of headache disorders, 3rd edition (beta version). Cephalalgia 33:629–808CrossRef

10.

Lipton RB, Bigal ME, Ashina S, Burstein R, Silberstein S, Reed ML et al (2008) Cutaneous allodynia in the migraine population. Ann Neurol 63:148–158CrossRef

11.

Seo JG, Park SP (2015) Validation of the patient health Questionnaire-9 (PHQ-9) and PHQ-2 in patients with migraine. J Headache Pain 16:65CrossRef

12.

Mykletun A, Stordal E, Dahl AA (2001) Hospital anxiety and depression (HAD) scale: factor structure, item analyses and internal consistency in a large population. Br J Psychiatry 179:540–544CrossRef

13.

Park BY, Byeon K, Park H (2019) FuNP (fusion of neuroimaging preprocessing) pipelines: a fully automated preprocessing software for functional magnetic resonance imaging. Front Neuroinform 13:5CrossRef

14.

Power JD, Barnes KA, Snyder AZ, Schlaggar BL, Petersen SE (2012) Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. Neuroimage 59:2142–2154CrossRef

15.

Salimi-Khorshidi G, Douaud G, Beckmann CF, Glasser MF, Griffanti L, Smith SM (2014) Automatic denoising of functional MRI data: combining independent component analysis and hierarchical fusion of classifiers. Neuroimage 90:449–468CrossRef

16.

Beckmann CF, DeLuca M, Devlin JT, Smith SM (2005) Investigations into resting-state connectivity using independent component analysis. Philos Trans R Soc Lond Ser B Biol Sci 360:1001–1013CrossRef

17.

Smith SM, Fox PT, Miller KL, Glahn DC, Fox PM, Mackay CE et al (2009) Correspondence of the brain's functional architecture during activation and rest. Proc Natl Acad Sci U S A 106:13040–13045CrossRef

18.

Griffanti L, Douaud G, Bijsterbosch J, Evangelisti S, Alfaro-Almagro F, Glasser MF et al (2017) Hand classification of fMRI ICA noise components. Neuroimage 154:188–205CrossRef

19.

Kelly RE Jr, Alexopoulos GS, Wang Z, Gunning FM, Murphy CF, Morimoto SS et al (2010) Visual inspection of independent components: defining a procedure for artifact removal from fMRI data. J Neurosci Methods 189:233–245CrossRef

20.

Yarkoni T, Poldrack RA, Nichols TE, Van Essen DC, Wager TD (2011) Large-scale automated synthesis of human functional neuroimaging data. Nat Methods 8:665–670CrossRef

21.

Smith SM, Miller KL, Salimi-Khorshidi G, Webster M, Beckmann CF, Nichols TE et al (2011) Network modelling methods for FMRI. Neuroimage 54:875–891CrossRef

22.

Mumford JA, Horvath S, Oldham MC, Langfelder P, Geschwind DH, Poldrack RA (2010) Detecting network modules in fMRI time series: a weighted network analysis approach. Neuroimage 52:1465–1476CrossRef

23.

Schwarz AJ, McGonigle J (2011) Negative edges and soft thresholding in complex network analysis of resting state functional connectivity data. Neuroimage 55:1132–1146CrossRef

24.

Rubinov M, Sporns O (2010) Complex network measures of brain connectivity: uses and interpretations. Neuroimage 52:1059–1069CrossRef

25.

Edlow BL, Takahashi E, Wu O, Benner T, Dai G, Bu L et al (2012) Neuroanatomic connectivity of the human ascending arousal system critical to consciousness and its disorders. J Neuropathol Exp Neurol 71:531–546CrossRef

26.

Denuelle M, Fabre N, Payoux P, Chollet F, Geraud G (2007) Hypothalamic activation in spontaneous migraine attacks. Headache 47:1418–1426PubMed

27.

Linnman C, Moulton EA, Barmettler G, Becerra L, Borsook D (2012) Neuroimaging of the periaqueductal gray: state of the field. Neuroimage 60:505–522CrossRef

28.

Ulrich M, Keller J, Gron G (2016) Dorsal raphe nucleus Down-regulates medial prefrontal cortex during experience of flow. Front Behav Neurosci 10:169CrossRef

29.

Beliveau V, Svarer C, Frokjaer VG, Knudsen GM, Greve DN, Fisher PM (2015) Functional connectivity of the dorsal and median raphe nuclei at rest. Neuroimage 116:187–195CrossRef

30.

Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B Methodol:289–300

31.

Chen C, Witte M, Heemsbergen W, van Herk M (2013) Multiple comparisons permutation test for image based data mining in radiotherapy. Radiat Oncol 8:293CrossRef

32.

Brodmann K, Vergleichende Lokalisationslehre der Grosshirnrinde in ihren Prinzipien dargestellt auf Grund des Zellenbaues. 1909: Barth

33.

Tzourio-Mazoyer N, Landeau B, Papathanassiou D, Crivello F, Etard O, Delcroix N et al (2002) Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage 15:273–289CrossRef

34.

Legrain V, Iannetti GD, Plaghki L, Mouraux A (2011) The pain matrix reloaded: a salience detection system for the body. Prog Neurobiol 93:111–124CrossRef

35.

Borsook D, Edwards R, Elman I, Becerra L, Levine J (2013) Pain and analgesia: the value of salience circuits. Prog Neurobiol 104:93–105CrossRef

36.

Bantick SJ, Wise RG, Ploghaus A, Clare S, Smith SM, Tracey I (2002) Imaging how attention modulates pain in humans using functional MRI. Brain 125:310–319CrossRef

37.

Goffaux P, Girard-Tremblay L, Marchand S, Daigle K, Whittingstall K (2014) Individual differences in pain sensitivity vary as a function of precuneus reactivity. Brain Topogr 27:366–374CrossRef

38.

Koyama T, McHaffie JG, Laurienti PJ, Coghill RC (2005) The subjective experience of pain: where expectations become reality. Proc Natl Acad Sci U S A 102:12950–12955CrossRef

39.

Seminowicz DA, Davis KD (2006) Cortical responses to pain in healthy individuals depends on pain catastrophizing. Pain 120:297–306CrossRef

40.

Schwedt TJ, Chong CD, Chiang CC, Baxter L, Schlaggar BL, Dodick DW (2014) Enhanced pain-induced activity of pain-processing regions in a case-control study of episodic migraine. Cephalalgia 34:947–958CrossRef

41.

Wager TD, Atlas LY, Lindquist MA, Roy M, Woo CW, Kross E (2013) An fMRI-based neurologic signature of physical pain. N Engl J Med 368:1388–1397CrossRef

42.

Malinen S, Vartiainen N, Hlushchuk Y, Koskinen M, Ramkumar P, Forss N et al (2010) Aberrant temporal and spatial brain activity during rest in patients with chronic pain. Proc Natl Acad Sci U S A 107:6493–6497CrossRef

43.

Chen Z, Chen X, Liu M, Dong Z, Ma L, Yu S (2017) Altered functional connectivity of amygdala underlying the neuromechanism of migraine pathogenesis. J Headache Pain 18:7CrossRef

44.

Cauda F, Sacco K, Duca S, Cocito D, D'Agata F, Geminiani GC et al (2009) Altered resting state in diabetic neuropathic pain. PLoS One 4:e4542CrossRef

45.

Napadow V, LaCount L, Park K, As-Sanie S, Clauw DJ, Harris RE (2010) Intrinsic brain connectivity in fibromyalgia is associated with chronic pain intensity. Arthritis Rheum 62:2545–2555CrossRef

46.

Becerra L, Sava S, Simons LE, Drosos AM, Sethna N, Berde C et al (2014) Intrinsic brain networks normalize with treatment in pediatric complex regional pain syndrome. Neuroimage Clin 6:347–369CrossRef

47.

Ichesco E, Schmidt-Wilcke T, Bhavsar R, Clauw DJ, Peltier SJ, Kim J et al (2014) Altered resting state connectivity of the insular cortex in individuals with fibromyalgia. J Pain 15:815–826 e1CrossRef

48.

Baliki MN, Mansour AR, Baria AT, Apkarian AV (2014) Functional reorganization of the default mode network across chronic pain conditions. PLoS One 9:e106133CrossRef

49.

Hamel E (2007) Serotonin and migraine: biology and clinical implications. Cephalalgia 27:1293–1300CrossRef

50.

Weiller C, May A, Limmroth V, Juptner M, Kaube H, Schayck RV et al (1995) Brain stem activation in spontaneous human migraine attacks. Nat Med 1:658–660CrossRef

51.

Goadsby PJ, Holland PR, Martins-Oliveira M, Hoffmann J, Schankin C, Akerman S (2017) Pathophysiology of migraine: a disorder of sensory processing. Physiol Rev 97:553–622CrossRef

Title: Increased connectivity of pain matrix in chronic migraine: a resting-state functional MRI study
Authors: Mi Ji Lee
Bo-yong Park
Soohyun Cho
Sung Tae Kim
Hyunjin Park
Chin-Sang Chung
Publication date: 01-12-2019
Publisher: Springer Milan
Keywords: Migraine
Headache
Published in: The Journal of Headache and Pain / Issue 1/2019
Print ISSN: 1129-2369
Electronic ISSN: 1129-2377
DOI: https://doi.org/10.1186/s10194-019-0986-z

At a glance: The STEP trials

Springer Medicine

Increased connectivity of pain matrix in chronic migraine: a resting-state functional MRI study

Abstract

Objective

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Objective

Methods

Results

Conclusion

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