A Single Session of rTMS Enhances Small-Worldness in Writer’s Cramp: Evidence from Simultaneous EEG-fMRI Multi-Modal Brain Graph

Background and Purpose: Repetitive transcranial magnetic stimulation (rTMS) induces widespread changes in brain connectivity. As the network topology differences induced by a single session of rTMS are less known we undertook this study to ascertain whether the network alterations had a small-world morphology using multi-modal graph theory analysis of simultaneous EEG-fMRI. Method: Simultaneous EEG-fMRI was acquired in duplicate before (R1) and after (R2) a single session of rTMS in 14 patients with Writer’s Cramp (WC). Whole brain neuronal and hemodynamic network connectivity were explored using the graph theory measures and clustering coefficient, path length and small-world index were calculated for EEG and resting state fMRI (rsfMRI). Multi-modal graph theory analysis was used to evaluate the correlation of EEG and fMRI clustering coefficients. Result: A single session of rTMS was found to increase the clustering coefficient and small-worldness significantly in both EEG and fMRI (p < 0.05). Multi-modal graph theory analysis revealed significant modulations in the fronto-parietal regions immediately after rTMS. The rsfMRI revealed additional modulations in several deep brain regions including cerebellum, insula and medial frontal lobe. Conclusion: Multi-modal graph theory analysis of simultaneous EEG-fMRI can supplement motor physiology methods in understanding the neurobiology of rTMS in vivo. Coinciding evidence from EEG and rsfMRI reports small-world morphology for the acute phase network hyper-connectivity indicating changes ensuing low-frequency rTMS is probably not “noise”.