Clinical Effects of Repetitive Transcranial Magnetic Stimulation of the Motor Cortex Are Associated With Changes in Resting-State Functional Connectivity in Patients With Fibromyalgia Syndrome

In this double-blinded, sham-controlled, counterbalanced, and crossover study, we investigated the potential neuroplasticity underlying pain relief and daily function improvements following repetitive transcranial magnetic stimulation of the motor cortex (M1-rTMS) in fibromyalgia syndrome (FMS) patients. Specifically, we used magnetic resonance imaging (MRI) to examine changes in brain structural and resting-state functional connectivity (rsFC) that correlated with improvements in FMS symptomology following M1-rTMS. Twenty-seven women with FMS underwent real and sham treatment series, each consisting of 10 daily treatments of 10Hz M1-rTMS over 2 weeks, with a washout period in between. Before and after each series, participants underwent anatomical and resting-state functional MRI scans and questionnaire assessments of FMS-related clinical pain and functional and psychological burdens. The expected reductions in FMS-related symptomology following M1-rTMS occurred with the real treatment only and correlated with rsFC changes in brain areas associated with pain processing and modulation. Specifically, between the ventromedial prefrontal cortex and the M1 (t = -5.54, corrected P = .002), the amygdala and the posterior insula (t = 5.81, corrected P = .044), and the anterior and posterior insula (t = 6.01, corrected P = .029). Neither treatment significantly changed brain structure. Therefore, we provide the first evidence of an association between the acute clinical effects of M1-rTMS in FMS and functional alterations of brain areas that have a significant role in the experience of chronic pain. Structural changes could potentially occur over a more extended treatment period. Perspective: We show that the neurophysiological mechanism of the improvement in fibromyalgia symptoms following active, but not sham, rTMS applied to M1 involves changes in resting-state functional connectivity in sensory, affective and cognitive pain processing brain areas, thus substantiating the essence of fibromyalgia syndrome as a treatable brain-based disorder.