title: rTMS affects working memory performance, brain activation and functional connectivity in patients with multiple sclerosis.
abstract: 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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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' brain function towards the healthy situation. This implicates a potentially relevant role for rTMS in cognitive rehabilitation in MS.
authors.affiliation: Department of Anatomy and Neurosciences, Section of Clinical Neuroscience, VUmc MS Center Amsterdam, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: H E
authors.initials: HE
authors.lastname: Hulst
authors.affiliation: Department of Anatomy and Neurosciences, Section of Clinical Neuroscience, VUmc MS Center Amsterdam, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Goldschmidt
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors, Dortmund, Germany.|Department Neurology, University Medical Hospital Bergmannsheil, Bochum, Germany.
authors.forename: M A
authors.identifier: 0000-0002-4764-1804
authors.initials: MA
authors.lastname: Nitsche
authors.affiliation: Department of Psychiatry, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: S J
authors.initials: SJ
authors.lastname: de Wit
authors.affiliation: Department of Anatomy and Neurosciences, Section of Clinical Neuroscience, VUmc MS Center Amsterdam, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.|Department of Psychiatry, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: O A
authors.initials: OA
authors.lastname: van den Heuvel
authors.affiliation: Department of Radiology and Nuclear Medicine, VUmc MS Center Amsterdam, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: Department of Clinical Neurophysiology, University of Göttingen, Gottingen, Germany.|Institutes of Neurology and Healthcare Engineering, UCL, London, United Kingdom.
authors.forename: W
authors.initials: W
authors.lastname: Paulus
authors.affiliation: Department of Anatomy and Neurosciences, Section of Clinical Neuroscience, VUmc MS Center Amsterdam, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Y D
authors.initials: YD
authors.lastname: van der Werf
authors.affiliation: Department of Anatomy and Neurosciences, Section of Clinical Neuroscience, VUmc MS Center Amsterdam, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: J J G
authors.initials: JJG
authors.lastname: Geurts
mesh_terms: D000328:Adult; D001931:Brain Mapping; D002421:Caudate Nucleus; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging* / Q000503:physiopathology; D009434:Neural Pathways / Q000502:physiology; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex; D050781:Transcranial Magnetic Stimulation / Q000379:methods*