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Effects of Cognitive-Behavioral Therapy (CBT) on Brain Connectivity Supporting Catastrophizing in Fibromyalgia

Lazaridou, Asimina PhD; Kim, Jieun PhD; Cahalan, Christine M. BSc; Loggia, Marco L. PhD; Franceschelli, Olivia BSc; Berna, Chantal MD; Schur, Peter MD; Napadow, Vitaly PhD; Edwards, Robert R. PhD

doi: 10.1097/AJP.0000000000000422
Original Articles

Objective(s): Fibromyalgia (FM) is a chronic, common pain disorder characterized by hyperalgesia. A key mechanism by which cognitive-behavioral therapy (CBT) fosters improvement in pain outcomes is via reductions in hyperalgesia and pain-related catastrophizing, a dysfunctional set of cognitive-emotional processes. However, the neural underpinnings of these CBT effects are unclear. Our aim was to assess CBT’s effects on the brain circuitry underlying hyperalgesia in FM patients, and to explore the role of treatment-associated reduction in catastrophizing as a contributor to normalization of pain-relevant brain circuitry and clinical improvement.

Methods: In total, 16 high-catastrophizing FM patients were enrolled in the study and randomized to 4 weeks of individual treatment with either CBT or a Fibromyalgia Education (control) condition. Resting state functional magnetic resonance imaging scans evaluated functional connectivity between key pain-processing brain regions at baseline and posttreatment. Clinical outcomes were assessed at baseline, posttreatment, and 6-month follow-up.

Results: Catastrophizing correlated with increased resting state functional connectivity between S1 and anterior insula. The CBT group showed larger reductions (compared with the education group) in catastrophizing at posttreatment (P<0.05), and CBT produced significant reductions in both pain and catastrophizing at the 6-month follow-up (P<0.05). Patients in the CBT group also showed reduced resting state connectivity between S1 and anterior/medial insula at posttreatment; these reductions in resting state connectivity were associated with concurrent treatment-related reductions in catastrophizing.

Discussion: The results add to the growing support for the clinically important associations between S1-insula connectivity, clinical pain, and catastrophizing, and suggest that CBT may, in part via reductions in catastrophizing, help to normalize pain-related brain responses in FM.

Departments of *Anesthesiology

§Medicine, Division of Rheumatology, Harvard Medical School, Brigham & Women’s Hospital, Chestnut Hill

MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA

Clinical Research Division, Korea Institute of Oriental Medicine, Daejeon, Korea

V.N. and R.R.E. contributed equally.

Supported by NIH grant R01-AR064367, by grants to RRE from the Arthritis Foundation and the American College of Rheumatology and grant P01-AT006663, R01-AT007550 to VN by the National Center for Complementary and Integrative Health (NCCIH). The project was carried out in part at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, Charlestown, MA, using resources provided by the Center for Functional Neuroimaging Technologies, P41EB015896, a P41 Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health and the KIOM grant K16051. The authors declare no conflict of interests.

Reprints: Robert R. Edwards, PhD, Brigham & Women’s Hospital, Pain Management Center, 850 Boylston St., Chestnut Hill, MA 02467 (e-mail:

Received December 5, 2015

Received in revised form August 11, 2016

Accepted July 16, 2016

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