Search

Question Transcranial magnetic stimulation (TMS) has become a promising therapeutic treatment and neuroscientific research tool, yet how it works is not fully understood. We developed a dedicated MR coil array positioned beneath the TMS coil that allows for concurrent stimulation and imaging and flexible positioning while ensuring TMS efficiency, high MR sensitivity and the use of parallel/multiband imaging sequences. Here we aimed to explain acute effects of TMS over left DLPFC using a new online TMS/fMRI setup in combination with advanced imaging and neuronavigation methods. Resting State functional connectivity and DTI Tractography shall further explain resulting activation patterns at a network level. Methods The study was performed on a 3T Tim Trio scanner (Siemens, Erlangen, Germany). The TMS system used included a MagProX100 stimulator and MRi-B91 MR-compatible TMS coil (Magventure, Farum, Denmark). Five right-handed female subjects (age: 28.6 ± 4.3 years) were examined. Functional images were acquired using EPI (echo-planar imaging) sequence with TR/TE = 1000/33 ms, 28 slices, 1.5 × 1.5 × 3mm3. The experimental procedure is depicted in Fig. 1. FMRI data analyses were performed using SPM12. The design matrix comprised four regressors representing different stimulation amplitudes. DTI tractography was performed using DSI Studio. Figure options Download full-size image Download high-quality image (729 K) Download as PowerPoint slide Results TMS led to intensity-dependent activation increase in the left DLPFC and the contralateral DLPFC ( Figure options Download full-size image Download high-quality image (874 K) Download as PowerPoint slide Fig. 2): Higher stimulation intensities evoked higher bilateral activation. ACC showed a more complex response pattern. Resting-state functional connectivity maps using the stimulation target as seed-voxel showed a network very similar to the TMS-derived activation pattern (Fig. 2). DTI tractography provided additional information about the axonal connection between the left DLPFC stimulation site and the right DLPFC activation cluster. Conclusion This is the first study to assess the acute influence of TMS over DLPFC at an individual level, made possible by a dedicated concurrent TMS/fMRI coil array. Here we show a dose-dependent increase in activity not only underneath the stimulation site but also on the contralateral homologous area and apparent mediating responses in the ACC. This network is confirmed by additional resting-state and tractography data.

Question While the precise mechanism of action is still unclear, rTMS is an effective FDA-approved treatment in depression and shows beneficial behavioral effects in a range of pathologies. A better understanding could improve treatment success and reduce the number of non-treatment responders. This study is the first to investigate effectiveness and specificity of rTMS over left DLPFC using a large-scale (n = 60) sham-controlled cross-over design and an unbiased resting-state (RS) approach. Methods 60 healthy subjects (age: 25.01 ± 4.6 years, f/m: 31/29) underwent rTMS DLPFC and sham stimulation (see Fig. 1) Download : Download high-res image (493KB) Download : Download full-size image . Resting state (rs) fMRI scans were acquired before and twice after stimulation. We investigated BOLD signal changes in functional connectivity (fc) following 10 Hz rTMS (24 × 5 s trains, ITI 20s, 1200 pulses @ 90%MT) during a classic resting state paradigm. We examined rsfc changes using an unbiased approach based on a set of 20 well-established resting state networks derived from multicenter-data independent component analysis by Biswal et al. (2010a, http://fcon_1000.projects.nitrc.org ). Results Comparisons between pre and post stimulation revealed that 19 out of a total of 20 IC networks remained unchanged, i.e. showed no statistically significant differences before and after rTMS irrespective of real/sham stimulation (Fig. 2 A, blue) Download : Download high-res image (1MB) Download : Download full-size image . Only one network (IC17, red dashed) which includes the ACC and PFC showed DLPFC rTMS-related connectivity changes (while staying stable throughout the whole procedure in sham session, Fig. 2 B): The ACC had increased connection strength in the post-rTMS scan within this network, particularly with the DLPFC (stimulation site), bilateral insula and striatum. Conclusion For the first time this study shows in a model-free approach that rTMS over left DLPFC modulates functional connectivity within a specific network while other networks stay stable. This network is typically associated with attention, mood, reward processing and psychiatric conditions that are linked to maladaptive changes in these domains. This could have further implications on treatment, screening and treatment response monitoring of psychiatric conditions.