title: The evolution of motor cortical dysfunction in amyotrophic lateral sclerosis.
abstract: The present study aimed to investigate alterations in cortical function in amyotrophic lateral sclerosis (ALS) related to disease progression.
  
  
  
  In total, clinical assessments were evaluated in 189 ALS patients, combined with assessment of cortical function utilising threshold tracking transcranial magnetic stimulation. Results were compared with disease stage. Disease stage was defined in three ways: (1) as a proportion of disease duration in deceased patients; (2) from the time of ALS onset; and (3) using the ALS rating scale-revised (ALSFRS-R).
  
  
  
  Prospective studies in ALS patients demonstrated decreased neurophysiological index (p<0.0001) and decreased compound muscle action potential (CMAP) (p<0.0001), combined with abnormalities of central function including prolonged central motor conduction time (CMCT) (p<0.05), increased motor evoked potential/CMAP amplitude ratio (p<0.0001) and decreased short interval intracortical inhibition (SICI) (p<0.001). SICI at 3ms (p<0.05, β=-0.21) and averaged SICI (p<0.05, β=-0.21) decreased with disease progression, measured using proportion of disease duration. Alternatively, using time from disease onset, CMCT prolonged with disease progression (p<0.01, β=0.25), while ALSFRS-R decline correlated with decreased SICI at 3ms (p<0.01, β=0.20).
  
  
  
  Clinical measures combined with assessment of cortical function established that SICI decreased with disease progression.
  
  
  
  These findings may suggest dysfunction of inhibitory interneurons with disease progression.
authors.affiliation: Brain and Mind Centre, University of Sydney, Australia.
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Shibuya
authors.affiliation: St. Vincent's Clinical School, University of Sydney, Australia.
authors.forename: Neil G
authors.initials: NG
authors.lastname: Simon
authors.affiliation: Western Clinical School, University of Sydney, Australia.
authors.forename: Nimeshan
authors.initials: N
authors.lastname: Geevasinga
authors.affiliation: Western Clinical School, University of Sydney, Australia.
authors.forename: Parvathi
authors.initials: P
authors.lastname: Menon
authors.affiliation: Brain and Mind Centre, University of Sydney, Australia.
authors.forename: James
authors.initials: J
authors.lastname: Howells
authors.affiliation: Brain and Mind Centre, University of Sydney, Australia.
authors.forename: Susanna B
authors.initials: SB
authors.lastname: Park
authors.affiliation: Brain and Mind Centre, University of Sydney, Australia; Prince of Wales Clinical School, University of New South Wales, Australia.
authors.forename: William
authors.initials: W
authors.lastname: Huynh
authors.affiliation: Brain and Mind Centre, University of Sydney, Australia.
authors.forename: Yu-Ichi
authors.initials: YI
authors.lastname: Noto
authors.affiliation: Western Clinical School, University of Sydney, Australia.
authors.forename: Steve
authors.initials: S
authors.lastname: Vucic
authors.affiliation: Brain and Mind Centre, University of Sydney, Australia. Electronic address: matthew.kiernan@sydney.edu.au.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Kiernan
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007395:Interneurons / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology*; D009046:Motor Neurons / Q000502:physiology; D009433:Neural Inhibition
keywords: Amyotrophic lateral sclerosis; Degeneration; Disease stage; Inhibitory interneuron; Intracortical inhibition; Transcranial magnetic stimulation