Theta-band EEG changes following sequential rTMS and tACS in fibromyalgia: A randomized controlled pilot study

Background: Sequential application of repetitive transcranial magnetic stimulation (rTMS) and transcranial alternating current stimulation (tACS) may induce neurophysiological changes within sensorimotor and pain-related networks. However, the resting-state EEG effects of this combined approach in fibromyalgia remain unknown. Methods: In this exploratory randomized controlled pilot study, 10 adults with fibromyalgia were assigned to active stimulation (n = 5) or a no-stimulation control group (n = 5). Active participants received one or two sessions of 10-Hz rTMS over the left primary motor cortex (1,000 pulses/session), followed by 10 daily sessions of bilateral 10-Hz tACS (1 mA, 20 min). Six-minute eyes-closed resting-state EEG recordings were obtained before and after the intervention or an equivalent control interval. Power spectral density was quantified in the delta, theta, alpha, and beta bands and analyzed using mixed repeated-measures ANOVAs across central-centroparietal and posterior regions of interest. Results: Theta power increased significantly in the active group but not in controls, yielding significant Time x Group (F(1,8)=8.70, p=.018, ηp2=.521) and Time x ROI x Group (F(1,8)=5.53, p=.047, ηp2=.409) interactions. Follow-up analyses showed increased theta power in both central-centroparietal (p=.004) and posterior (p=.012) regions, with a larger increase observed posteriorly. No significant interaction effects were found for delta, alpha, or beta power. Conclusions: Sequential motor-cortex rTMS followed by repeated bilateral 10-Hz tACS was associated with increased resting-state theta activity in fibromyalgia. Given the small sample size, post hoc ROI selection, lack of sham stimulation, and absence of component-specific control conditions, these findings should be considered hypothesis-generating and require replication in adequately powered sham-controlled studies.