P 82. Dose-dependent effects of theta-burst rTMS on the cortical excitability and fMRI-connectivity of the primary motor cortex

Abstract

Introduction Theta Burst Stimulation (TBS) is an effective rTMS-protocol to modulate the excitability of cortical motor regions (Huang et al., 2005). However, the effects between subjects are rather variable (Hamda et al., 2012). The reason for this variability is still unclear (Thickbroom, 2007). Recently, animal studies showed that there are dose-dependent effects of TBS on the expression of cellular proteins (Volz et al., 2010). In contrast, studies with human subjects did not find a consistent dose–effect after applying two TBS sessions serially at different intersession intervals (Gamboa et al., 2010, 2011). Objectives The aim of our study was to investigate the effect of a triple TBS session on the cortical excitability compared to a control-stimulation. By combining TBS with functional magnetic resonance imaging (fMRI) measurements we sought to reveal stimulation effects on cortical connectivity. Methods 15 healthy subjects received three stimulations according to the iTBS-protocol (600 pulses per stimulation, (Huang et al., 2005)). iTBS sessions were applied in a serial fashion spaced by intervals of 15min. Two different stimulation sites were tested at different days: primary motor cortex (M1) and the parieto-occipital cortex (control). Stimulation after-effects on cortical excitability were tested via stimulus–response curves. In separate stimulation sessions, the iTBS effects on fMRI-connectivity were tested for two conditions: (i) resting-state measurements and (ii) during thumb movements. The following motor areas were included in the network analysis: M1, supplementary motor area (SMA), dorsal and ventral premotor cortex (dPMC, vPMC), anterior intraparietal cortex, putamen, thalamus and cerebellum. Results We found a dose-dependent effect of iTBS on the height of the stimulus–response-curve with significantly higher MEPs after applying iTBS over M1 compared to the control-stimulation. The connectivity-analyses revealed that after M1 stimulation with 1800 pulses the effective connectivity of the ipsilateral dPMC to the stimulated M1 was significantly enhanced while the control-stimulation had no differential effect on cortical connectivity ( p Conclusions Our results suggest that the after-effects of iTBS are dose-dependent. Furthermore, our data show that iTBS of M1 leads to a higher integration of the stimulated area with premotor areas.