@article {Hulst386, author = {H E Hulst and T Goldschmidt and M A Nitsche and S J de Wit and O A van den Heuvel and F Barkhof and W Paulus and Y D van der Werf and J J G Geurts}, title = {rTMS affects working memory performance, brain activation and functional connectivity in patients with multiple sclerosis}, volume = {88}, number = {5}, pages = {386--394}, year = {2017}, doi = {10.1136/jnnp-2016-314224}, publisher = {BMJ Publishing Group Ltd}, abstract = {Objective To investigate the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the right dorsolateral prefrontal cortex (DLPFC) on working memory performance, while measuring task-related brain activation and task-related brain connectivity in patients with multiple sclerosis (MS).Methods 17 patients with MS and 11 healthy controls (HCs) underwent 3 experimental sessions (baseline, real-rTMS, sham-rTMS), all including an N-back task (3 task loads: N1, N2, N3; control condition: N0) inside the MR scanner. Prior to imaging, real-rTMS (10 Hz) was applied to the right DLPFC. The stimulation site was defined based on individually assessed N-back task activation at baseline and located using neuronavigation. Changes in whole brain functional activation and functional connectivity with the right DLPFC were calculated.Results N-back task accuracy (N2 and N3) improved after real-rTMS (and not after sham-rTMS) compared with baseline (p=0.029 and p=0.015, respectively), only in patients. At baseline, patients with MS, compared with HCs, showed higher task-related frontal activation (left DLPFC, N2\>N0), which disappeared after real-rTMS. Task-related (N1\>N0) functional connectivity between the right DLPFC and the right caudate nucleus and bilateral (para)cingulate gyrus increased in patients after real-rTMS when compared with sham stimulation.Conclusions In patients with MS, N-back accuracy improved while frontal hyperactivation (seen at baseline relative to HCs) disappeared after real-rTMS. Together with the changes in functional connectivity after real-rTMS in patients, these findings may represent an rTMS-induced change in network efficiency in patients with MS, shifting patients{\textquoteright} brain function towards the healthy situation. This implicates a potentially relevant role for rTMS in cognitive rehabilitation in MS.}, issn = {0022-3050}, URL = {https://jnnp.bmj.com/content/88/5/386}, eprint = {https://jnnp.bmj.com/content/88/5/386.full.pdf}, journal = {Journal of Neurology, Neurosurgery \& Psychiatry} }