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Changes in resting-state brain networks after cognitive–behavioral therapy for chronic pain

  • A. Yoshino (a1), Y. Okamoto (a1), G. Okada (a1), M. Takamura (a1), N. Ichikawa (a1), C. Shibasaki (a1), S. Yokoyama (a1), M. Doi (a2), R. Jinnin (a1), H. Yamashita (a1), M. Horikoshi (a3) and S. Yamawaki (a1)...



Cognitive–behavioral therapy (CBT) is thought to be useful for chronic pain, with the pathology of the latter being closely associated with cognitive–emotional components. However, there are few resting-state functional magnetic resonance imaging (R-fMRI) studies. We used the independent component analysis method to examine neural changes after CBT and to assess whether brain regions predict treatment response.


We performed R-fMRI on a group of 29 chronic pain (somatoform pain disorder) patients and 30 age-matched healthy controls (T1). Patients were enrolled in a weekly 12-session group CBT (T2). We assessed selected regions of interest that exhibited differences in intrinsic connectivity network (ICN) connectivity strength between the patients and controls at T1, and compared T1 and T2. We also examined the correlations between treatment effects and rs-fMRI data.


Abnormal ICN connectivity of the orbitofrontal cortex (OFC) and inferior parietal lobule within the dorsal attention network (DAN) and of the paracentral lobule within the sensorimotor network in patients with chronic pain normalized after CBT. Higher ICN connectivity strength in the OFC indicated greater improvements in pain intensity. Furthermore, ICN connectivity strength in the dorsal posterior cingulate cortex (PCC) within the DAN at T1 was negatively correlated with CBT-related clinical improvements.


We conclude that the OFC is crucial for CBT-related improvement of pain intensity, and that the dorsal PCC activation at pretreatment also plays an important role in improvement of clinical symptoms via CBT.


Corresponding author

Author for correspondence: A. Yoshino, E-mail:


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Anderson, MJ and Robinson, J (2001) Permutation tests for linear models. Australian & New Zealand Journal of Statistics 43, 7588.
APA (1994) Diagnostic and Statistical Manual of Mental Disorders: DSM-IV. Washington, DC: Amer Psychiatric Pub Inc.
Baker, KS, Georgiou-Karistianis, N, Gibson, SJ and Giummarra, MJ (2017) Optimizing cognitive function in persons With chronic pain. The Clinical Journal of Pain 33, 462472.
Beck, A, Brown, G and Steer, R (1996) Beck Depression Inventory-II Manual. San Antonio: Psychological Corporation.
Calhoun, V, Adali, T, Pearlson, G and Pekar, J (2001) A method for making group inferences from functional MRI data using independent component analysis. Human Brain Mapping 14, 140151.
Catley, MJ, O'Connell, NE, Berryman, C, Ayhan, FF and Moseley, GL (2014) Is tactile acuity altered in people with chronic pain? A systematic review and meta-analysis. Journal of Pain 15, 9851000.
Chen, H-J, Chen, Q-F, Liu, J and Shi, H-B (2016) Aberrant salience network and its functional coupling with default and executive networks in minimal hepatic encephalopathy: a resting-state fMRI study. Scientific Reports 6, 27092.
Chou, K-H, Yang, F-C, Fuh, J-L, Kuo, C-Y, Wang, Y-H, Lirng, J-F et al. (2016) Bout-associated intrinsic functional network changes in cluster headache: a longitudinal resting-state functional MRI study. Cephalalgia, Epub ahead of print. DOI: 10.1177/0333102416668657.
Crowther, A, Smoski, MJ, Minkel, J, Moore, T, Gibbs, D, Petty, C et al. (2015) Resting-state connectivity predictors of response to psychotherapy in major depressive disorder. Neuropsychopharmacology 40, 16591673.
Dhond, RP, Yeh, C, Park, K, Kettner, N and Napadow, V (2008) Acupuncture modulates resting state connectivity in default and sensorimotor brain networks. Pain 136, 407418.
First, MB, Spitzer, RL, Gibbon, M and Williams, JB (2012) Structured Clinical Interview for DSM-IV® Axis I Disorders (SCID-I), Clinician Version, Administration Booklet. New York: American Psychiatric Pub.
Fox, MD and Raichle, ME (2007) Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nature Reviews Neuroscience 8, 700711.
Fox, MD, Snyder, AZ, Vincent, JL, Corbetta, M, Van Essen, DC and Raichle, ME (2005) The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proceedings of the National Academy of Sciences USA 102, 96739678.
Hayasaka, S and Nichols, TE (2004) Combining voxel intensity and cluster extent with permutation test framework. NeuroImage 23, 5463.
Honey, C, Sporns, O, Cammoun, L, Gigandet, X, Thiran, J-P, Meuli, R et al. (2009) Predicting human resting-state functional connectivity from structural connectivity. Proceedings of the National Academy of Sciences USA 106, 20352040.
Jacobs, RH, Watkins, ER, Peters, AT, Feldhaus, CG, Barba, A, Carbray, J et al. (2016) Targeting ruminative thinking in adolescents at risk for depressive relapse: rumination-focused cognitive behavior therapy in a pilot randomized controlled trial with resting state fMRI. PLoS ONE 11, e0163952.
Jensen, KB, Kosek, E, Wicksell, R, Kemani, M, Olsson, G, Merle, JV et al. (2012) Cognitive behavioral therapy increases pain-evoked activation of the prefrontal cortex in patients with fibromyalgeia. Pain 153, 14951503.
Juottonen, K, Gockel, M, Silén, T, Hurri, H, Hari, R and Forss, N (2002) Altered central sensorimotor processing in patients with complex regional pain syndrome. Pain 98, 315323.
Kaichi, Y, Okada, G, Takamura, M, Toki, S, Akiyama, Y, Higaki, T et al. (2016) Changes in the regional cerebral blood flow detected by arterial spin labeling after 6-week escitalopram treatment for major depressive disorder. Journal of Affective Disorders 194, 135143.
Kregel, J, Meeus, M, Malfliet, A, Dolphens, M, Danneels, L, Nijs, J et al. (2015) Structural and functional brain abnormalities in chronic low back pain: a systematic review. Seminars in Arthritis and Rheumatism 45, 229237.
Kumari, V, Peters, ER, Fannon, D, Antonova, E, Premkumar, P, Anilkumar, AP et al. (2009) Dorsolateral prefrontal cortex activity predicts responsiveness to cognitive–behavioral therapy in schizophrenia. Biological Psychiatry 66, 594602.
Leech, R and Sharp, DJ (2014) The role of the posterior cingulate cortex in cognition and disease. Brain 137, 1232.
Lipowski, ZJ (1988) Somatization: the concept and its clinical application. American Journal of Psychiatry 145, 13581368.
Loggia, ML, Kim, J, Gollub, RL, Vangel, MG, Kirsch, I, Kong, J et al. (2013) Default mode network connectivity encodes clinical pain: an arterial spin labeling study. Pain 154, 2433.
Mason, L, Peters, E and Kumari, V (2016) Functional connectivity predictors and mechanisms of cognitive behavioural therapies: a systematic review with recommendations. Australian and New Zealand Journal of Psychiatry 50, 311321.
Melzack, R (1987) The short-form McGill pain questionnaire. Pain 30, 191197.
Menon, V (2011) Large-scale brain networks and psychopathology: a unifying triple network model. Trends in Cognitive Sciences 15, 483506.
Neugebauer, V, Galhardo, V, Maione, S and Mackey, SC (2009) Forebrain pain mechanisms. Brain Research Reviews 60, 226242.
Raichle, ME (2011) The restless brain. Brain Connect 1, 312.
Seidel, EM, Pfabigan, DM, Hahn, A, Sladky, R, Grahl, A, Paul, K et al. (2015) Uncertainty during pain anticipation: the adaptive value of preparatory processes. Human Brain Mapping 36, 744755.
Seminowicz, DA and Davis, KD (2007) Pain enhances functional connectivity of a brain network evoked by performance of a cognitive task. Journal of Neurophysiology 97, 36513659.
Seminowicz, DA, Shpaner, M, Keaser, ML, Krauthamer, GM, Mantegna, J, Dumas, JA et al. (2013) Cognitive-behavioral therapy increases prefrontal cortex gray matter in patients with chronic pain. The Journal of Pain 14, 15731584.
Sheline, YI, Price, JL, Yan, Z and Mintun, MA (2010) Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus. Proceedings of the National Academy of Sciences USA 107, 1102011025.
Shpaner, M, Kelly, C, Lieberman, G, Perelman, H, Davis, M, Keefe, FJ et al. (2014) Unlearning chronic pain: a randomized controlled trial to investigate changes in intrinsic brain connectivity following cognitive behavioral therapy. NeuroImage: Clinical 5, 365376.
Simons, LE, Elman, I and Borsook, D (2014) Psychological processing in chronic pain: a neural systems approach. Neuroscience & Biobehavioral Reviews 39, 6178.
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. Proceedings of the National Academy of Sciences USA 106, 1304013045.
Spielberger, CD (1983) Manual for the State-Trait Anxiety Inventory STAI (Form Y)(‘Self-Evaluation Questionnaire’). Palo Alto, CA: Consulting Psychologists Press.
Spreng, RN, Mar, RA and Kim, AS (2009) The common neural basis of autobiographical memory, prospection, navigation, theory of mind, and the default mode: a quantitative meta-analysis. Journal of Cognitive Neuroscience 21, 489510.
Sullivan, MJL, Bishop, SR and Pivik, J (1995) The pain catastrophizing scale: development and validation. Psychological Assessment 7, 524532.
Tamura, Y, Okabe, S, Ohnishi, T, Saito, DN, Arai, N, Mochio, S et al. (2004) Effects of 1-Hz repetitive transcranial magnetic stimulation on acute pain induced by capsaicin. Pain 107, 107115.
Wager, TD, Atlas, LY, Leotti, LA and Rilling, JK (2011) Predicting individual differences in placebo analgesia: contributions of brain activity during anticipation and pain experience. Journal of Neuroscience 31, 439452.
Williams, A, Eccleston, C and Morley, S (2012) Psychological therapies for the management of chronic pain (excluding headache) in adults. Cochrane Database of Systematic Reviews 11.
Wu, T-H, Tu, C-H, Chao, H-T, Li, W-C, Low, I, Chuang, C-Y et al. (2016) Dynamic changes of functional pain connectome in women with primary dysmenorrhea. Scientific Reports 6, 24543.
Yanagisawa, T, Fukuma, R, Seymour, B, Hosomi, K, Kishima, H, Shimizu, T et al. (2016) Induced sensorimotor brain plasticity controls pain in phantom limb patients. Nature Communications 7, 13209.
Yoshino, A, Okamoto, Y, Horikoshi, M, Oshita, K, Nakamura, R, Otsuru, N et al. (2015) Effectiveness of group cognitive behavioral therapy (GCBT) for somatoform pain disorder patients in Japan: a preliminary non-case-control study. Psychiatry and Clinical Neurosciences 69, 763772.
Yoshino, A, Okamoto, Y, Kunisato, Y, Yoshimura, S, Jinnin, R, Hayashi, Y et al. (2014) Distinctive spontaneous regional neural activity in patients with somatoform pain disorder: a preliminary resting-state fMRI study. Psychiatry Research: Neuroimaging 221, 246248.
Yoshino, A, Okamoto, Y, Yoshimura, S, Shishida, K, Toki, S, Doi, M et al. (2013) Distinctive neural responses to pain stimuli during induced sadness in patients with somatoform pain disorder: an fMRI study. Neuroimage: Clinical 2, 782789.


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