title: Long-term effects of contralesional rTMS in severe stroke: safety, cortical excitability, and relationship with transcallosal motor fibers.
abstract: BACKGROUND
  Contralesional hemispheric repetitive transcranial magnetic stimulation (rTMS) may improve motor function in mild to moderate stroke and effects are considered to be mediated through transcallosal motor fibers.
  
  
  OBJECTIVE
  This study aimed to investigate the safety of contralesional rTMS in a selected group of severe chronic stroke patients.
  
  
  METHODS
  Ten sessions of 1 Hz rTMS were applied to contralesional primary motor cortex (M1) using neuronavigated stimulation and changes in motor impairment were evaluated before, during and after rTMS applications and at 4-weeks follow-up. Neurophysiological response to stimulation was assessed through cortical excitability evaluations. The relationship between functional and neurophysiological response to rTMS and microstructural integrity of transcallosal motor fibers were searched using diffusion tensor imaging (DTI) based fractional anisotropy (FA).
  
  
  RESULTS
  rTMS was well-tolerated with high compliance and no dropouts; no seizures or motor worsening occurred. Transcallosal FA values revealed a positive linear relationship with the mild motor improvement detected after rTMS while higher FA values were observed in subjects with better motor outcome. Cortical excitability showed a significant change in contralesional short-interval intracortical inhibition indicating altered plasticity following rTMS.
  
  
  CONCLUSIONS
  Our results suggest that noninvasive neuromodulation of the contralesional hemisphere may present a possibility to assist adaptive neuroplastic changes in severe chronic stroke. Implementation of DTI-derived measures of transcallosal microstructural integrity may allow for individually-tailored interventions to guide processes of interhemispheric neuroplasticity. Further research is warranted to establish the clinical value of these findings in neurorehabilitation settings for subjects with chronic severe stroke.
authors.affiliation: Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul University, Istanbul Medical Faculty, Istanbul, Turkey.
authors.forename: Asli
authors.initials: A
authors.lastname: Demirtas-Tatlidede
authors.affiliation: Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Miguel
authors.initials: M
authors.lastname: Alonso-Alonso
authors.affiliation: Center for Biomedical Imaging, Boston University, Boston, MA, USA.
authors.forename: Ravi P
authors.initials: RP
authors.lastname: Shetty
authors.affiliation: Center for Biomedical Imaging, Boston University, Boston, MA, USA Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Itamar
authors.initials: I
authors.lastname: Ronen
authors.affiliation: Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Pascual-Leone
authors.affiliation: Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Laboratory of Neuromodulation, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Felipe
authors.initials: F
authors.lastname: Fregni
mesh_terms: D000328:Adult; D000368:Aged; D002540:Cerebral Cortex / Q000503:physiopathology*; D003337:Corpus Callosum; D056324:Diffusion Tensor Imaging; D005260:Female; D005500:Follow-Up Studies; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology*; D009046:Motor Neurons / Q000473:pathology*; D000071939:Stroke Rehabilitation; D013997:Time Factors; D050781:Transcranial Magnetic Stimulation / Q000009:adverse effects / Q000379:methods*; D016896:Treatment Outcome
keywords: Severe stroke; cerebrovascular disease; cortical excitability; diffusion tensor imaging (DTI); neurorehabilitation; repetitive transcranial magnetic stimulation (rTMS)