Abstract
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”.
Highlights
Repetitive transcranial magnetic stimulation influences brain functional organization as well as task performance probably by modulating network connectivity beyond the stimulation period and zone (Yoo et al, 2008; Park et al, 2014) and has found a therapeutic role in several neurodegenerative diseases (Chou et al, 2015)
Clinical studies have found modulations induced by Repetitive transcranial magnetic stimulation (rTMS) to be site specific with improvement in clinical scores in Writer’s cramp (WC; Murase et al, 2005) and primary cervical dystonia (Pirio Richardson et al, 2015) associated with low-frequency rTMS over the primary motor cortex and not over supplementary motor cortex
Molecular imaging with PET using [11C] FLB 457 has reported modulations induced by rTMS to be disease specific as it has found increased dopamine release in the orbitofrontal cortices in Parkinson’s disease (Cho and Strafella, 2009) and reduced dopamine production in basal ganglia of healthy controls (HCs; Ko et al, 2008), following high-frequency stimulation of the left dorso-lateral prefrontal cortex
Summary
Repetitive transcranial magnetic stimulation (rTMS) influences brain functional organization as well as task performance probably by modulating network connectivity beyond the stimulation period and zone (Yoo et al, 2008; Park et al, 2014) and has found a therapeutic role in several neurodegenerative diseases (Chou et al, 2015). Based on the evidence of the long-lasting clinical benefits following rTMS, several biological studies have proposed rTMS induced alterations to occur at neuronal, synaptic and genetic levels (Okano and Ohkubo, 2003; McKay et al, 2007; Pazur et al, 2007) by mechanisms like long-term potentiation (LTP) and long-term depression (LTD; Chervyakov et al, 2015). Clinical studies have found modulations induced by rTMS to be site specific with improvement in clinical scores in Writer’s cramp (WC; Murase et al, 2005) and primary cervical dystonia (Pirio Richardson et al, 2015) associated with low-frequency rTMS over the primary motor cortex and not over supplementary motor cortex. 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
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