title: A model of the contribution of late I-waves to α-motoneuronal activation: implications for paired-pulse TMS.
abstract: BACKGROUND
  In paired-pulse (conditioned-test) transcranial magnetic stimulation (TMS) protocols, the effect of the conditioning pulse on the test response can be substantial. Epidural recordings indicate that this is mediated through modulation of late indirect (I-) wave volleys. It is not well understood how strong effect sizes could arise from the later, and usually weaker, I-wave volleys.
  
  
  OBJECTIVE
  To formulate a model of I-wave summation at the spinal level to explore the contribution of late I-waves to the activation of the α-motoneuronal pool and to paired-pulse TMS measures of intracortical inhibition and facilitation.
  
  
  METHODS
  I-wave recruitment curves were modeled for the first three I-waves. A series of steps converted I-wave inputs to α-motoneuronal activation. The role of I₃ in activating the α-motoneuronal pool was investigated by manipulating the amplitude of the I₃ volley.
  
  
  RESULTS
  For all TMS intensities, I₃ made a contribution to the firing of the α-motoneuronal pool that was disproportional to its contribution to the descending volley. At its most influential, I₃ increased the descending volley by 23.5% but increased the proportion of motoneurons that fired by 567%. There was a U-like relationship to stimulus intensity with inhibition of I₃, and an inverted-U relationship for facilitation of I₃, in keeping with empirical observation. Changes in spinal excitability disproportionally influenced α-motoneuronal recruitment.
  
  
  CONCLUSIONS
  Late I-waves have a pivotal role in determining the response to paired-pulse TMS. The spinal transfer function that converts I-wave input to α-motoneuron activation can amplify the role of late I-waves and potentially influence paired-pulse TMS measures of intracortical inhibition and facilitation.
authors.affiliation: Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Nedlands, Western Australia, Australia. gthickbr@cyllene.uwa.edu.au
authors.forename: Gary W
authors.initials: GW
authors.lastname: Thickbroom
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006801:Humans; D008959:Models, Neurological; D009046:Motor Neurons / Q000502:physiology*; D050781:Transcranial Magnetic Stimulation / Q000379:methods*