title: A model of TMS-induced I-waves in motor cortex.
abstract: BACKGROUND
  Transcranial magnetic stimulation (TMS) allows to manipulate neural activity non-invasively, and much research is trying to exploit this ability in clinical and basic research settings. In a standard TMS paradigm, single-pulse stimulation over motor cortex produces repetitive responses in descending motor pathways called I-waves. However, the details of how TMS induces neural activity patterns in cortical circuits to produce these responses remain poorly understood. According to a traditional view, I-waves are due to repetitive synaptic inputs to pyramidal neurons in layer 5 (L5) of motor cortex, but the potential origin of such repetitive inputs is unclear.
  
  
  OBJECTIVE
  Here we aim to test the plausibility of an alternative mechanism behind D- and I-wave generation through computational modeling. This mechanism relies on the broad distribution of conduction delays of synaptic inputs arriving at different parts of L5 cells' dendritic trees and their spike generation mechanism.
  
  
  METHODS
  Our model consists of a detailed L5 pyramidal cell and a population of layer 2 and 3 (L2/3) neurons projecting onto it with synapses exhibiting short-term depression. I-waves are simulated as superpositions of spike trains from a large population of L5 cells.
  
  
  RESULTS
  Our model successfully reproduces all basic characteristics of I-waves observed in epidural responses during in vivo recordings of conscious humans. In addition, it shows how the complex morphology of L5 neurons might play an important role in the generation of I-waves. In the model, later I-waves are formed due to inputs to distal synapses, while earlier ones are driven by synapses closer to the soma. Finally, the model offers an explanation for the inhibition and facilitation effects in paired-pulse stimulation protocols.
  
  
  CONCLUSIONS
  In contrast to previous models, which required either neural oscillators or chains of inhibitory interneurons acting upon L5 cells, our model is fully feed-forward without lateral connections or loops. It parsimoniously explains findings from a range of experiments and should be considered as a viable alternative explanation of the generating mechanism of I-waves.
authors.affiliation: Frankfurt Institute for Advanced Studies, Frankfurt am Main, Germany; Center for Cognitive and Neural Studies (Coneural), Romanian Institute of Science and Technology, Cluj-Napoca, Romania; Department of Computer Science, Babeş-Bolyai University, Cluj-Napoca, Romania.
authors.forename: Cătălin V
authors.initials: CV
authors.lastname: Rusu
authors.affiliation: Frankfurt Institute for Advanced Studies, Frankfurt am Main, Germany; Department of Physics, Goethe University, Frankfurt am Main, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Murakami
authors.affiliation: Department of Neurology & Stroke, and Hertie-Institute for Clinical Brain Research, Eberhard Karls University, Tübingen, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Ziemann
authors.affiliation: Frankfurt Institute for Advanced Studies, Frankfurt am Main, Germany; Department of Physics, Goethe University, Frankfurt am Main, Germany. Electronic address: triesch@fias.uni-frankfurt.de.
authors.forename: Jochen
authors.initials: J
authors.lastname: Triesch
mesh_terms: D002540:Cerebral Cortex / Q000502:physiology*; D003712:Dendrites / Q000502:physiology; D004824:Epidural Space / Q000473:pathology; D006801:Humans; D007395:Interneurons; D007477:Ions / Q000737:chemistry; D007700:Kinetics; D008564:Membrane Potentials; D008959:Models, Neurological; D009044:Motor Cortex / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D016011:Normal Distribution; D013569:Synapses / Q000502:physiology; D013997:Time Factors; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D005680:gamma-Aminobutyric Acid / Q000737:chemistry
chemical_list: D007477:Ions; D005680:gamma-Aminobutyric Acid
keywords: Computational model; I-waves; Motor cortex; Neuron; Transcranial stimulation