title: Cortical Damage and Disability in Multiple Sclerosis: Relation to Intracortical Inhibition and Facilitation.
abstract: Multimodal research combining biomarkers of intracortical activity and cortical damage could shed light on pathophysiological and adaptive neural processes related to the clinical severity of neurological conditions such as multiple sclerosis (MS).
  
  
  
  Among people with relapsing-remitting and progressive forms of MS, we assessed the extent to which transcranial magnetic stimulation (TMS)-based biomarkers of excitatory and inhibitory cortical activity are related to cortical damage and clinical impairment.
  
  
  
  Participants included 18 healthy individuals and 36 people with MS who had a relapsing-remitting or progressive clinical course. Using TMS, intracortical facilitation (ICF), short-interval intracortical inhibition (SICI), long-interval intracortical inhibition (LICI), and cortical silent period (CSP) were obtained. Cortical volume and cortical magnetization transfer ratio (MTR) were quantified. Disability was assessed with Multiple Sclerosis Functional Composite (MSFC).
  
  
  
  Lower mean MTR within the cerebral cortex correlated with shorter CSP among MS participants with a progressive, but not a relapsing-remitting, clinical course. Within the cortical hand knob region targeted with TMS, lower MTR was correlated with lower SICI only among individuals with relapsing-remitting MS. Longer CSP, higher ICF, lower cortical MTR, and sex were all independent significant predictors of poor upper extremity motor performance, while only cortical MTR was a significant independent predictor of total MSFC score among people with MS.
  
  
  
  Cortical damage and cortical activity (both inhibitory and excitatory) may contribute to the severity of motor disability experienced by people with MS. When interpreting TMS-based outcomes, cortical integrity, clinical course, and symptom type should be considered.
authors.affiliation: Integrated Program in Neuroscience, McGill University, 3801 University Street, Room 141, Montreal, Quebec H3A 2B4, Canada; Research Institute of the McGill University Health Centre, 2155 Guy Street, 5th Floor, Montreal, Quebec H3H 2R9, Canada. Electronic address: julia.nantes@mail.mcgill.ca.
authors.forename: Julia C
authors.initials: JC
authors.lastname: Nantes
authors.affiliation: Research Institute of the McGill University Health Centre, 2155 Guy Street, 5th Floor, Montreal, Quebec H3H 2R9, Canada; Department of Neurology and Neurosurgery, McGill University, 845 Rue Sherbrooke Ouest, Montreal, Quebec, Canada.
authors.forename: Jidan
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Integrated Program in Neuroscience, McGill University, 3801 University Street, Room 141, Montreal, Quebec H3A 2B4, Canada; Research Institute of the McGill University Health Centre, 2155 Guy Street, 5th Floor, Montreal, Quebec H3H 2R9, Canada.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Holmes
authors.affiliation: Department of Neurology and Neurosurgery, McGill University, 845 Rue Sherbrooke Ouest, Montreal, Quebec, Canada; Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, Quebec H3A 2B4, Canada.
authors.forename: Sridar
authors.initials: S
authors.lastname: Narayanan
authors.affiliation: Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, Quebec H3A 2B4, Canada.
authors.forename: Yves
authors.initials: Y
authors.lastname: Lapierre
authors.affiliation: Research Institute of the McGill University Health Centre, 2155 Guy Street, 5th Floor, Montreal, Quebec H3H 2R9, Canada; Department of Neurology and Neurosurgery, McGill University, 845 Rue Sherbrooke Ouest, Montreal, Quebec, Canada.
authors.forename: Lisa
authors.initials: L
authors.lastname: Koski
mesh_terms: D000328:Adult; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D009433:Neural Inhibition / Q000502:physiology*; D050781:Transcranial Magnetic Stimulation
keywords: Cortical damage; Disability progression; Intracortical facilitation; Intracortical inhibition; Magnetization transfer ratio; Multiple sclerosis; Transcranial magnetic stimulation