Effect of Repetitive Transcranial Magnetic Stimulation on the Symptoms and Brain Imaging in Patients with Fibromyalgia Syndrome: A Randomized Controlled Pilot Trial

Abstract

Introduction: Repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) has been shown to reduce the symptoms of patients with fibromyalgia syndrome (FMS). We tested whether rTMS of the left DLPFC can reduce the main symptoms in FMS and whether TMS induces changes in brain functional and structural connectivity, cortical gray matter volume, and the metabolites/neurotransmitters GABA and combined glutamate/glutamine (Glx).

Methods: Twenty-seven women diagnosed with FMS according to the 2010 ACR criteria were included in a randomized controlled trial. They received either ten sessions of active or sham 10-Hz stimulation over 2 weeks embedded in a longitudinal neuroimaging setup, including one pre-treatment (T1), one post-treatment (T2), and one follow-up (T3) 3 T MRI scan. Pain and pain catastrophizing, depression, daily life/quality of life, and anxiety were assessed using standard questionnaires.

Results: Linear mixed-model analysis of clinical data showed a significant main effect of the main factor time but did not reveal group differences or group-time interactions, indicating a large placebo effect with symptom reduction in both groups. Fractional anisotropy (FA) values of the pontine crossing tract, the sagittal stratum, and the right cingulum in the active rTMS group increased between pre-TMS and the follow-up time points. Subgroup analysis of responders of the treatment group revealed higher functional connectivity between the left DLPFC and the right cerebellum. We did not find evidence for changes in the treatment group in the gray matter of the left DLPFC and for the concentrations of GABA and Glx, but a trend towards decreasing Glx levels for the factor time in all patients could be detected.

Conclusions: While these results may be due to small sample size and short treatment duration, the findings of increased FA after active rTMS and higher functional connectivity between DLPFC and cerebellum in responders should be further explored.

Trial registration: Auswirkungen der nicht-invasiven Neuromodulation auf das Gehirn bei Fibromyalgiepatienten.

Drks-id: DRKS00019051.

Keywords: Brain imaging; Diffusion tensor imaging; Dorsolateral prefrontal cortex; Fibromyalgia syndrome; Gray matter volume; HF-rTMS; Neuromodulation; Pain; Proton MR spectroscopy; Resting-state functional MRI.