ArticleCognitive Behavioral Therapy increases pain-evoked activation of the prefrontal cortex in patients with fibromyalgeiaJensen, Karin B.a,b,*; Kosek, Evac,d; Wicksell, Rikardc,e; Kemani, Mikec,e; Olsson, Gunnare,f; Merle, Julia V.g; Kadetoff, Dianac,d; Ingvar, Martinc,d Author Information Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. aDepartment of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA bAthinoula A. Martinos Center for Biomedical Imaging, Boston, MA, USA cDepartment of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden dOsher Center for Integrative Medicine, Karolinska Institutet, Stockholm, Sweden eBehavior Medicine Pain Treatment Services, Karolinska University Hospital, Stockholm, Sweden fDepartment of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden gDepartment of Child and Adolescent Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany *Corresponding author. Address: Massachusetts General Hospital, Harvard Medical School, Psychiatric Neuroimaging Building, 120 Second Avenue, Charlestown, MA 02129, USA. Tel.: +1 617 756 7491; fax: +1 617 643 7340. E-mail address:[email protected] Article history: Received 30 September 2011; Received in revised form 10 April 2012; Accepted 10 April 2012. Pain 153(7):p 1495-1503, July 2012. | DOI: 10.1016/j.pain.2012.04.010 Buy Metrics Abstract Summary Treatment with Cognitive Behavioral Therapy leads to clinical improvements in fibromyalgia patients, paired with increased activity and connectivity in the brain’s pain modulatory regions. Interventions based on Cognitive Behavioral Therapy (CBT) are widely used to treat chronic pain, but the brain mechanisms responsible for these treatment effects are poorly understood. The aim of this study was to validate the relevance of the cortical control theory in response to an exposure-based form of CBT, Acceptance and Commitment Therapy, in patients with chronic pain. Forty-three female patients diagnosed with fibromyalgia syndrome were enrolled in a randomized, 12-week, waiting-list controlled clinical trial (CBT n = 25; controls n = 18). CBT was administered in groups of six patients during 12 weekly sessions. Functional magnetic resonance imaging (fMRI) during pressure-evoked pain was assessed before and after treatment or the 12-week period. Self-report questionnaires of depression and anxiety were administered pre- and posttreatment as well as 3 months following end of treatment. Patients treated with CBT reported larger improvement of fibromyalgia on the Patient Global Impression of Change measure, and improved depression and anxiety symptoms, compared to the waiting-list controls. However, there were no effects on clinical pain or pain sensitivity measures. An analysis of fMRI scans revealed that CBT led to increased activations in the ventrolateral prefrontal/lateral orbitofrontal cortex; regions associated with executive cognitive control. We suggest that CBT changes the brain’s processing of pain through an altered cerebral loop between pain signals, emotions, and cognitions; leading to increased access to executive regions for reappraisal of pain. Our data thereby support our hypothesis about the activation of a cortical control mechanism in response to CBT treatment in chronic pain. © 2012 Lippincott Williams & Wilkins, Inc.