Abstract
Cortical functioning within the default mode network (DMN) and salience network (SN) is altered in chronic pain patients. The mechanisms underlying these alterations are unknown, but a novel unexamined source is cross-network communication. Aberrant functional connectivity (FC) between the DMN and SN, whose activity is normally anticorrelated, reflects disease severity in many brain disorders. Further, stronger FC between the posterior cingulate cortex (PCC) and anterior insula has been reported in chronic pain, pointing to abnormal DMN–SN interactions. Here, we tested the hypothesis that cross-network FC between the DMN and SN is abnormal in chronic pain, and is related to pain and associated symptoms. We used resting state fMRI to examine FC within and between the DMN and SN in 20 patients with chronic pain due to ankylosing spondylitis and 20 healthy controls. A whole-network analysis revealed that compared to healthy controls, patients exhibited less anticorrelated FC between the SN and DMN, and the degree of cross-network abnormality tracked pain and disease-related symptoms. This suggests that cross-network FC is a metric of functional brain abnormality in chronic pain. In a complementary seed-based analysis, the PCC was strongly connected with the SN and weakly connected with the DMN in chronic pain compared to healthy controls, suggesting that the PCC acts as a hub for altered network interaction. Sensorimotor cortex cross-network FC correlated with measures of physical function, suggesting that physical functioning also impacts brain network interaction in chronic pain. Our study implicates altered communication between brain networks as a key factor underlying chronic pain.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Andrews-Hanna JR, Reidler JS, Sepulcre J, Poulin R, Buckner RL (2010) Functional-anatomic fractionation of the brain’s default network. Neuron 65(4):550–562. doi:10.1016/j.neuron.2010.02.005
Apkarian VA, Sosa Y, Krauss BR, Thomas SP, Fredrickson BE, Levy RE, Harden NR, Chialvo DR (2004) Chronic pain patients are impaired on an emotional decision-making task. Pain 108(1):129–136. doi:10.1016/j.pain.2003.12.015
Apkarian AV, Hashmi JA, Baliki MN (2011) Pain and the brain: specificity and plasticity of the brain in clinical chronic pain. Pain 152(3):S49–S64. doi:10.1016/j.pain.2010.11.010
Attal N, Masselin-Dubois A, Martinez V, Jayr C, Albi A, Fermanian J, Bouhassira D, Baudic S (2014) Does cognitive functioning predict chronic pain? Results from a prospective surgical cohort. Brain 137(3):904–917. doi:10.1093/brain/awt354
Baldassarre A, Ramsey L, Hacker CL, Callejas A, Astafiev SV, Metcalf NV, Zinn K, Rengachary J, Snyder AZ, Carter AR, Shulman GL, Corbetta M (2014) Large-scale changes in network interactions as a physiological signature of spatial neglect. Brain 137(12):3267–3283. doi:10.1093/brain/awu297
Baliki MN, Chialvo DR, Geha PY, Levy RM, Harden RN, Parrish TB, Apkarian AV (2006) Chronic pain and the emotional brain: specific brain activity associated with spontaneous fluctuations of intensity of chronic back pain. J Neurosci 26(47):12165–12173. doi:10.1523/jneurosci.3576-06.2006
Baliki MN, Geha PY, Apkarian AV, Chialvo DR (2008) Beyond feeling: chronic pain hurts the brain, disrupting the default-mode network dynamics. J Neurosci 28(6):1398–1403. doi:10.1523/jneurosci.4123-07.2008
Baliki MN, Baria AT, Apkarian AV (2011) The cortical rhythms of chronic back pain. J Neurosci 31(39):13981–13990. doi:10.1523/jneurosci.1984-11.2011
Baliki MN, Mansour AR, Baria AT, Apkarian AV (2014) Functional reorganization of the default mode network across chronic pain conditions. PLoS One 9(9). doi:10.1371/journal.pone.0106133
Balthazar MLF, Pereira FRS, Lopes TM, da Silva EL, Coan AC, Campos BM, Duncan NW, Stella F, Northoff G, Damasceno BP, Cendes F (2014) Neuropsychiatric symptoms in Alzheimer’s disease are related to functional connectivity alterations in the salience network: NPS in AD and functional connectivity alterations of SN. Hum Brain Mapp 35(4):1237–1246. doi:10.1002/hbm.22248
Becerra L, Sava S, Simons LE, Drosos AM, Sethna N, Berde C, Lebel AA, Borsook D (2014) Intrinsic brain networks normalize with treatment in pediatric complex regional pain syndrome. Neuroimage Clin 6:347–369. doi:10.1016/j.nicl.2014.07.012
Behzadi Y, Restom K, Liau J, Liu TT (2007) A component based noise correction method (CompCor) for BOLD and perfusion based fMRI. NeuroImage 37(1):90–101. doi:10.1016/j.neuroimage.2007.04.042
Berman MG, Nee DE, Casement M, Kim HS, Deldin P, Kross E, Gonzalez R, Demiralp E, Gotlib IH, Hamilton P, Joormann J, Waugh C, Jonides J (2011) Neural and behavioral effects of interference resolution in depression and rumination. Cogn Affect Behav Neurosci 11(1):85–96. doi:10.3758/s13415-010-0014-x
Bonnelle V, Ham TE, Leech R, Kinnunen KM, Mehta MA, Greenwood RJ, Sharp DJ (2012) Salience network integrity predicts default mode network function after traumatic brain injury. Proc Natl Acad Sci 109(12):4690–4695. doi:10.1073/pnas.1113455109
Borsook D, Edwards R, Elman I, Becerra L, Levine J (2013) Pain and analgesia: the value of salience circuits. Prog Neurobiol 104:93–105. doi:10.1016/j.pneurobio.2013.02.003
Brier MR, Thomas JB, Snyder AZ, Benzinger TL, Zhang D, Raichle ME, Holtzman DM, Morris JC, Ances BM (2012) Loss of intranetwork and internetwork resting state functional connections with Alzheimer’s disease progression. J Neurosci 32(26):8890–8899. doi:10.1523/jneurosci.5698-11.2012
Castellanos FX, Margulies DS, Kelly C, Uddin LQ, Ghaffari M, Kirsch A, Shaw D, Shehzad Z, Di Martino A, Biswal B, Sonuga-Barke EJS, Rotrosen J, Adler LA, Milham MP (2008) Cingulate-precuneus interactions: a new locus of dysfunction in adult attention-deficit/hyperactivity disorder. Biol Psychiatry 63(3):332–337. doi:10.1016/j.biopsych.2007.06.025
Cauda F, Sacco K, Duca S, Cocito D, D’Agata F, Geminiani GC, Canavero S (2009) Altered resting state in diabetic neuropathic pain. PLoS One 4(2):e4542
Chai XJ, Castañón AN, Ongür D, Whitfield-Gabrieli S (2012) Anticorrelations in resting state networks without global signal regression. NeuroImage 59(2):1420–1428. doi:10.1016/j.neuroimage.2011.08.048
Cho H, Kim T, Kim T-H, Lee S, Lee KH (2013) Spinal mobility, vertebral squaring, pulmonary function, pain, fatigue, and quality of life in patients with ankylosing spondylitis. Ann Rehabil Med 37(5):675–682. doi:10.5535/arm.2013.37.5.675
Critchley HD (2005) Neural mechanisms of autonomic, affective, and cognitive integration. J Comp Neurol 493(1):154–166. doi:10.1002/cne.20749
Davis KD, Moayedi M (2013) Central mechanisms of pain revealed through functional and structural MRI. J Neuroimmune Pharmacol 8(3):518–534. doi:10.1007/s11481-012-9386-8
Domján L, Nemes T, Bálint G, Tóth Z, Gömör B (1990) A simple method for measuring lateral flexion of the dorsolumbar spine. J Rheumatol 17(5):663–665
Downar J, Crawley AP, Mikulis DJ, Davis KD (2000) A multimodal cortical network for the detection of changes in the sensory environment. Nat Neurosci 3(3):277–283. doi:10.1038/72991
Downar J, Mikulis DJ, Davis KD (2003) Neural correlates of the prolonged salience of painful stimulation. NeuroImage 20(3):1540–1551. doi:10.1016/s1053-8119(03)00407-5
Erpelding N, Davis KD (2013) Neural underpinnings of behavioural strategies that prioritize either cognitive task performance or pain. Pain 154(10):2060–2071. doi:10.1016/j.pain.2013.06.030
Farmer MA, Baliki MN, Apkarian AV (2012) A dynamic network perspective of chronic pain. Neurosci Lett 520(2):197–203. doi:10.1016/j.neulet.2012.05.001
Fox MD, Raichle ME (2007) Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci 8(9):700–711. doi:10.1038/nrn2201
Fox MD, Snyder AZ, Vincent JL, Corbetta M, Van Essen DC, Raichle ME (2005) The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci USA 102(27):9673–9678. doi:10.1073/pnas.0504136102
Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A (1994) A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol 21(12):2286–2291
Gay CW, Robinson ME, George SZ, Perlstein WM, Bishop MD (2014) Immediate changes after manual therapy in resting-state functional connectivity as measured by functional magnetic resonance imaging in participants with induced low back pain. J Manip Physiol Ther 37(9):614–627. doi:10.1016/j.jmpt.2014.09.001
Gupta A, Rapkin AJ, Gill Z, Kilpatrick L, Fling C, Stains J, Masghati S, Tillisch K, Mayer EA, Labus JS (2015) Disease-related differences in resting state networks: a comparison between localized provoked vulvodynia, irritable bowel syndrome, and healthy control subjects. Pain. doi:10.1097/01.j.pain.0000461289.65571.54
Hashmi JA, Baliki MN, Huang L, Baria AT, Torbey S, Hermann KM, Schnitzer TJ, Apkarian AV (2013) Shape shifting pain: chronification of back pain shifts brain representation from nociceptive to emotional circuits. Brain 136(9):2751–2768. doi:10.1093/brain/awt211
Hemington KS, Coulombe M-A (2015) The periaqueductal gray and descending pain modulation: why should we study them and what role do they play in chronic pain? J Neurophysiol. doi:10.1152/jn.00998.2014
Hoekzema E, Carmona S, Ramos-Quiroga JA, Richarte Fernández V, Bosch R, Soliva JC, Rovira M, Bulbena A, Tobeña A, Casas M, Vilarroya O (2014) An independent components and functional connectivity analysis of resting state fMRI data points to neural network dysregulation in adult ADHD. Hum Brain Mapp 35(4):1261–1272. doi:10.1002/hbm.22250
Hong JY, Kilpatrick LA, Labus JS, Gupta A, Katibian D, Ashe-McNalley C, Stains J, Heendeniya N, Smith SR, Tillisch K, Naliboff B, Mayer EA (2014) Sex and disease-related alterations of anterior insula functional connectivity in chronic abdominal pain. J Neurosci 34(43):14252–14259. doi:10.1523/jneurosci.1683-14.2014
Hubbard CS, Khan SA, Keaser ML, Mathur VA, Goyal M, Seminowicz DA (2014) Altered brain structure and function correlate with disease severity and pain catastrophizing in migraine patients. Eneuro 1(1). doi:10.1523/eneuro.0006-14.2014
Ichesco E, Schmidt-Wilcke T, Bhavsar R, Clauw DJ, Peltier SJ, Kim J, Napadow V, Hampson JP, Kairys AE, Williams DA, Harris RE (2014) Altered resting state connectivity of the insular cortex in individuals with fibromyalgia. J Pain 15(8):815–826.e811. doi:10.1016/j.jpain.2014.04.007
Jenkinson TR, Mallorie PA, Whitelock HC, Kennedy LG, Garrett SL, Calin A (1994) Defining spinal mobility in ankylosing spondylitis (AS). The Bath AS Metrology Index. J Rheumatol 21(9):1694–1698
Jenkinson M, Beckmann CF, Behrens TEJ, Woolrich MW (2012) FSL. NeuroImage 62(2):782–790. doi:10.1016/j.neuroimage.2011.09.015
Jilka SR, Scott G, Ham T, Pickering A, Bonnelle V, Braga RM, Leech R, Sharp DJ (2014) Damage to the salience network and interactions with the default mode network. J Neurosci 34(33):10798–10807. doi:10.1523/jneurosci.0518-14.2014
Kelly AMC, Uddin LQ, Biswal BB, Castellanos FX, Milham MP (2008) Competition between functional brain networks mediates behavioral variability. NeuroImage 39(1):527–537. doi:10.1016/j.neuroimage.2007.08.008
Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD (1989) The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol 46(10):1121–1123
Kucyi A, Davis KD (2014) Dynamic functional connectivity of the default mode network tracks daydreaming. NeuroImage 100:471–480. doi:10.1016/j.neuroimage.2014.06.044
Kucyi A, Davis KD (2015) The dynamic pain connectome. Trends Neurosci 38(2):86–95. doi:10.1016/j.tins.2014.11.006
Kucyi A, Hodaie M, Davis KD (2012) Lateralization in intrinsic functional connectivity of the temporoparietal junction with salience- and attention-related brain networks. J Neurophysiol 108(12):3382–3392. doi:10.1152/jn.00674.2012
Kucyi A, Salomons TV, Davis KD (2013) Mind wandering away from pain dynamically engages antinociceptive and default mode brain networks. Proc Natl Acad Sci 110(46):18692–18697. doi:10.1073/pnas.1312902110
Kucyi A, Moayedi M, Weissman-Fogel I, Goldberg MB, Freeman BV, Tenenbaum HC, Davis KD (2014) Enhanced medial prefrontal-default mode network functional connectivity in chronic pain and its association with pain rumination. J Neurosci 34(11):3969–3975. doi:10.1523/jneurosci.5055-13.2014
Kucyi A, Hove MJ, Biederman J, Van Dijk KRA, Valera EM (2015) Disrupted functional connectivity of cerebellar default network areas in attention-deficit/hyperactivity disorder: cerebellar Default Network and ADHD. Hum Brain Mapp. doi:10.1002/hbm.22850
Liddle EB, Hollis C, Batty MJ, Groom MJ, Totman JJ, Liotti M, Scerif G, Liddle PF (2011) Task-related default mode network modulation and inhibitory control in ADHD: effects of motivation and methylphenidate: default mode network modulation in ADHD. J Child Psychol Psychiatry 52(7):761–771. doi:10.1111/j.1469-7610.2010.02333.x
Linden SVD, Valkenburg HA, Cats A (1984) Evaluation of diagnostic criteria for ankylosing spondylitis. Arthritis Rheum 27(4):361–368
Loggia ML, Kim J, Gollub RL, Vangel MG, Kirsch I, Kong J, Wasan AD, Napadow V (2013) Default mode network connectivity encodes clinical pain: an arterial spin labeling study. PAIN® 154(1):24–33. doi:10.1016/j.pain.2012.07.029
Mathur VA, Khan SA, Keaser ML, Hubbard CS, Goyal M, Seminowicz DA (2015) Altered cognition-related brain activity and interactions with acute pain in migraine. Neuroimage Clin 7:347–358. doi:10.1016/j.nicl.2015.01.003
Mattfeld AT, Gabrieli JDE, Biederman J, Spencer T, Brown A, Kotte A, Kagan E, Whitfield-Gabrieli S (2014) Brain differences between persistent and remitted attention deficit hyperactivity disorder. Brain 137(9):2423–2428. doi:10.1093/brain/awu137
Menon V (2011) Large-scale brain networks and psychopathology: a unifying triple network model. Trends Cogn Sci 15(10):483–506. doi:10.1016/j.tics.2011.08.003
Menon V, Uddin LQ (2010) Saliency, switching, attention and control: a network model of insula function. Brain Struct Funct 214(5–6):655–667. doi:10.1007/s00429-010-0262-0
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(8):2545–2555. doi:10.1002/art.27497
Otti A, Guendel H, Wohlschläger A, Zimmer C, Noll-Hussong M (2013) Frequency shifts in the anterior default mode network and the salience network in chronic pain disorder. BMC Psychiatry 13:84. doi:10.1186/1471-244X-13-84
Pievani M, Filippini N, van den Heuvel MP, Cappa SF, Frisoni GB (2014) Brain connectivity in neurodegenerative diseases—from phenotype to proteinopathy. Nat Rev Neurol 10(11):620–633. doi:10.1038/nrneurol.2014.178
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(3):2142–2154. doi:10.1016/j.neuroimage.2011.10.018
Power JD, Schlaggar BL, Petersen SE (2015) Recent progress and outstanding issues in motion correction in resting state fMRI. NeuroImage 105:536–551. doi:10.1016/j.neuroimage.2014.10.044
Qiu E, Tian L, Wang Y, Ma L, Yu S (2015) Abnormal coactivation of the hypothalamus and salience network in patients with cluster headache. Neurology 84(14):1402–1408. doi:10.1212/wnl.0000000000001442
Rocca MA, Valsasina P, Martinelli V, Misci P, Falini A, Comi G, Filippi M (2012) Large-scale neuronal network dysfunction in relapsing-remitting multiple sclerosis. Neurology 79(14):1449–1457
Rocca MA, Valsasina P, Absinta M, Moiola L, Ghezzi A, Veggiotti P, Amato MP, Horsfield MA, Falini A, Comi G, Filippi M (2014) Intranetwork and internetwork functional connectivity abnormalities in pediatric multiple sclerosis: large-scale neuronal networks in pediatric MS. Hum Brain Mapp 35(8):4180–4192. doi:10.1002/hbm.22469
Seeley WW, Menon V, Schatzberg AF, Keller J, Glover GH, Kenna H, Reiss AL, Greicius MD (2007) Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci 27(9):2349–2356. doi:10.1523/jneurosci.5587-06.2007
Seidler R, Erdeniz B, Koppelmans V, Hirsiger S, Mérillat S, Jäncke L (2015) Associations between age, motor function, and resting state sensorimotor network connectivity in healthy older adults. NeuroImage 108:47–59. doi:10.1016/j.neuroimage.2014.12.023
Seminowicz DA, Davis KD (2007) Pain enhances functional connectivity of a brain network evoked by performance of a cognitive task. J Neurophysiol 97(5):3651–3659. doi:10.1152/jn.01210.2006
Seminowicz DA, Wideman TH, Naso L, Hatami-Khoroushahi Z, Fallatah S, Ware MA, Jarzem P, Bushnell MC, Shir Y, Ouellet JA, Stone LS (2011) Effective treatment of chronic low back pain in humans reverses abnormal brain anatomy and function. J Neurosci 31(20):7540–7550. doi:10.1523/jneurosci.5280-10.2011
Sharp TJ, Harvey AG (2001) Chronic pain and posttraumatic stress disorder: mutual maintenance? Clin Psychol Rev 21(6):857–877
Sharp DJ, Beckmann CF, Greenwood R, Kinnunen KM, Bonnelle V, De Boissezon X, Powell JH, Counsell SJ, Patel MC, Leech R (2011) Default mode network functional and structural connectivity after traumatic brain injury. Brain 134(8):2233–2247. doi:10.1093/brain/awr175
Sharp DJ, Scott G, Leech R (2014) Network dysfunction after traumatic brain injury. Nat Rev Neurol 10(3):156–166. doi:10.1038/nrneurol.2014.15
Shirer WR, Ryali S, Rykhlevskaia E, Menon V (2012) Decoding subject-driven cognitive states with whole-brain connectivity patterns. Cereb Cortex 22(1):158–165. doi:10.1093/cercor/bhr099
Smith SM, Jenkinson M, Woolrich MW, Beckmann CF (2004) Advances in functional and structural MR image analysis and implementation as FSL. NeuroImage 23:S208–S219. doi:10.1016/j.neuroimage.2004.07.051
Sridharan D, Levitin DJ, Menon V (2008) A critical role for the right fronto-insular cortex in switching between central-executive and default-mode networks. Proc Natl Acad Sci 105(34):12569–12574
Sripada RK, King AP, Welsh RC, Garfinkel SN, Wang X, Sripada CS, Liberzon I (2012) Neural dysregulation in posttraumatic stress disorder: evidence for disrupted equilibrium between salience and default mode brain networks. Psychosom Med 74(9):904–911. doi:10.1097/PSY.0b013e318273bf33
Stagg NJ, Mata HP, Ibrahim MM, Henriksen EJ, Porreca F, Vanderah TW, Malan TP Jr (2011) Regular exercise reverses sensory hypersensitivity in a rat neuropathic pain model. Anesthesiology 114(4):940–948. doi:10.1097/ALN.0b013e318210f880
Stubbs B, Schofield P, Patchay S (2014) Mobility limitations and fall-related factors contribute to the reduced health-related quality of life in older adults with chronic musculoskeletal pain. Pain Pract. doi:10.1111/papr.12264
Sullivan MJLB, Scott R, Pivik Jayne (1995) The Pain Catastrophizing Scale: development and validation. Psychol Assess 7(4):524–532
Sun L, Cao Q, Long X, Sui M, Cao X, Zhu C, Zuo X, An L, Song Y, Zang Y, Wang Y (2012) Abnormal functional connectivity between the anterior cingulate and the default mode network in drug-naïve boys with attention deficit hyperactivity disorder. Psychiatry Res 201(2):120–127. doi:10.1016/j.pscychresns.2011.07.001
Sundermann B, Burgmer M, Pogatzki-Zahn E, Gaubitz M, Stüber C, Wessolleck E, Heuft G, Pfleiderer B (2014) Diagnostic classification based on functional connectivity in chronic pain: model optimization in fibromyalgia and rheumatoid arthritis. Acad Radiol 21(3):369–377. doi:10.1016/j.acra.2013.12.003
Tagliazucchi E, Balenzuela P, Fraiman D, Chialvo DR (2010) Brain resting state is disrupted in chronic back pain patients. Neurosci Lett 485(1):26–31. doi:10.1016/j.neulet.2010.08.053
Uddin LQ (2015) Salience processing and insular cortical function and dysfunction. Nat Rev Neurosci 16(1):55–61. doi:10.1038/nrn3857
van der Heijde D, Breban M, Halter D, DiVittorio G, Bratt J, Cantini F, Kary S, Pangan AL, Kupper H, Rathmann SS, Sieper J, Mease PJ (2014) Maintenance of improvement in spinal mobility, physical function and quality of life in patients with ankylosing spondylitis after 5 years in a clinical trial of adalimumab. Rheumatology (Oxford). doi:10.1093/rheumatology/keu438
Van Dijk KRA, Sabuncu MR, Buckner RL (2012) The influence of head motion on intrinsic functional connectivity MRI. NeuroImage 59(1):431–438. doi:10.1016/j.neuroimage.2011.07.044
Viisanen H, Pertovaara A (2010) Roles of the rostroventromedial medulla and the spinal 5-HT1A receptor in descending antinociception induced by motor cortex stimulation in the neuropathic rat. Neurosci Lett 476(3):133–137. doi:10.1016/j.neulet.2010.04.014
Weissman-Fogel I, Moayedi M, Tenenbaum HC, Goldberg MB, Freeman BV, Davis KD (2011) Abnormal cortical activity in patients with temporomandibular disorder evoked by cognitive and emotional tasks. Pain 152(2):384–396. doi:10.1016/j.pain.2010.10.046
Whitfield-Gabrieli S, Ford JM (2012) Default mode network activity and connectivity in psychopathology. Annu Rev Clin Psychol 8(1):49–76. doi:10.1146/annurev-clinpsy-032511-143049
Worsley KJ, Liao CH, Aston J, Petre V (2002) A general statistical analysis for fMRI data. NeuroImage 15(1):1–15. doi:10.1006/nimg.2001.0933
Wu Q, Inman RD, Davis KD (2013) Neuropathic pain in ankylosing spondylitis: a psychophysics and brain imaging study: neuropathic pain in AS. Arthritis Rheum 65(6):1494–1503. doi:10.1002/art.37920
Wu Q, Inman RD, Davis KD (2014) Fatigue in ankylosing spondylitis is associated with the brain networks of sensory salience and attention: neuroimaging of fatigue-associated brain networks in AS. Arthritis Rheumatol 66(2):295–303. doi:10.1002/art.38244
Wu Q, Inman RD, Davis KD (2015) Tumor necrosis factor inhibitor therapy in ankylosing spondylitis: differential effects on pain and fatigue and brain correlates. Pain 156(2):297–304. doi:10.1097/01.j.pain.0000460310.71572.16
Zhang D, Raichle ME (2010) Disease and the brain’s dark energy. Nat Rev Neurol 6(1):15–28. doi:10.1038/nrneurol.2009.198
Zhang S, Wu W, Huang G, Liu Z, Guo S, Yang J, Wang K (2014) Resting-state connectivity in the default mode network and insula during experimental low back pain. Neural Regen Res 9(2):135–142. doi:10.4103/1673-5374.125341
Acknowledgments
This work was supported by Canada Research Chair Program (CRC in Brain and Behaviour) and a CIHR Operating Grant for KDD. Q. Wu was a recipient of the Pain Scientist Scholarship, University of Toronto Center for the Study of Pain, and the Postdoctoral Fellowship, Canadian Pain Society. K.S.H. is the recipient of a Queen Elizabeth II/Purdue Pharma Scholarship in Science and Technology, and an Arthritis Society of Canada Scholarship. The authors thank the participants for volunteering their time. We also thank Adele Carty and Renise Ayearst for clinical data retrieval, Ammepa Anton for patient recruitment, Eugene Hlasny and Keith Ta for expert technical assistance with MRI acquisition, and Joshua Cheng and Marie-Andrée Coulombe for data analysis assistance.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors have no conflicts of interest to declare.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Hemington, K.S., Wu, Q., Kucyi, A. et al. Abnormal cross-network functional connectivity in chronic pain and its association with clinical symptoms. Brain Struct Funct 221, 4203–4219 (2016). https://doi.org/10.1007/s00429-015-1161-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00429-015-1161-1