Patients with fibromyalgia (FM) show characteristically enhanced unpleasantness to painful and nonpainful sensations accompanied by altered neural responses. The diagnostic potential of such neural alterations, including their sensitivity and specificity to FM (vs healthy controls) is unknown. We identify a brain signature that characterizes FM central pathophysiology at the neural systems level. We included 37 patients with FM and 35 matched healthy controls, and analyzed functional magnetic resonance imaging responses to (1) painful pressure and (2) nonpainful multisensory (visual–auditory–tactile) stimulation. We used machine-learning techniques to identify a brain-based FM signature. When exposed to the same painful stimuli, patients with FM showed greater neurologic pain signature (NPS; Wager et al., 2013. An fMRI-based neurologic signature of physical pain. N Engl J Med 2013;368:1388–97) responses. In addition, a new pain-related classifier (“FM-pain”) revealed augmented responses in sensory integration (insula/operculum) and self-referential (eg, medial prefrontal) regions in FM and reduced responses in the lateral frontal cortex. A “multisensory” classifier trained on nonpainful sensory stimulation revealed augmented responses in the insula/operculum, posterior cingulate, and medial prefrontal regions and reduced responses in the primary/secondary sensory cortices, basal ganglia, and cerebellum. Combined activity in the NPS, FM pain, and multisensory patterns classified patients vs controls with 92% sensitivity and 94% specificity in out-of-sample individuals. Enhanced NPS responses partly mediated mechanical hypersensitivity and correlated with depression and disability (Puncorrected < 0.05); FM-pain and multisensory responses correlated with clinical pain (Puncorrected < 0.05). The study provides initial characterization of individual patients with FM based on pathophysiological, symptom-related brain features. If replicated, these brain features may constitute objective neural targets for therapeutic interventions. The results establish a framework for assessing therapeutic mechanisms and predicting treatment response at the individual level.
Supplemental Digital Content is Available in the Text.We identified an initial functional magnetic resonance imaging-based neural signature that identifies out-of-sample patients with fibromyalgia (vs healthy controls) with 92% sensitivity and 94% specificity and correlates with symptom severity.
aDepartment of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA
bInstitute of Cognitive Science, University of Colorado Boulder, Boulder, CO, USA
cMRI Research Unit, Department of Radiology, Hospital del Mar, CIBERSAM G21, Barcelona, Spain
dDepartment of Clinical and Health Psychology, Autonomous University of Barcelona, Barcelona, Spain
eGuttmann Neurorehabilitation Institute, Autonomous University of Barcelona, Spain
fMelbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Victoria, Australia
gDepartment of Rheumatology, Hospital del Mar, Barcelona, Spain
Corresponding author. Address: Department of Psychology and Neuroscience, University of Colorado Boulder, 345 UCB, Boulder, CO 80305, USA. Tel.: (303) 492 4299; fax: (303) 492 2967. E-mail address: email@example.com (M. López-Solà).
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
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Received January 20, 2016
Received in revised form August 18, 2016
Accepted August 24, 2016