TY - JOUR A1 - Seo, Hyeon A1 - Schaworonkow, Natalie A1 - Jun, Sung Chan A1 - Triesch, Jochen T1 - A multi-scale computational model of the effects of TMS on motor cortex [version 1; referees: 2 approved with reservations] T2 - F1000Research N2 - The detailed biophysical mechanisms through which transcranial magnetic stimulation (TMS) activates cortical circuits are still not fully understood. Here we present a multi-scale computational model to describe and explain the activation of different cell types in motor cortex due to transcranial magnetic stimulation. Our model determines precise electric fields based on an individual head model derived from magnetic resonance imaging and calculates how these electric fields activate morphologically detailed models of different neuron types. We predict detailed neural activation patterns for different coil orientations consistent with experimental findings. Beyond this, our model allows us to predict activation thresholds for individual neurons and precise initiation sites of individual action potentials on the neurons’ complex morphologies. Specifically, our model predicts that cortical layer 3 pyramidal neurons are generally easier to stimulate than layer 5 pyramidal neurons, thereby explaining the lower stimulation thresholds observed for I-waves compared to D-waves. It also predicts differences in the regions of activated cortical layer 5 and layer 3 pyramidal cells depending on coil orientation. Finally, it predicts that under standard stimulation conditions, action potentials are mostly generated at the axon initial segment of corctial pyramidal cells, with a much less important activation site being the part of a layer 5 pyramidal cell axon where it crosses the boundary between grey matter and white matter. In conclusion, our computational model offers a detailed account of the mechanisms through which TMS activates different cortical cell types, paving the way for more targeted application of TMS based on individual brain morphology in clinical and basic research settings. KW - transcranial magnetic stimulation KW - computational model KW - compartmental neuron model KW - brain stimulation KW - multi-scale modeling KW - motor cortex KW - D-wave KW - I-wave Y1 - 2016 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/47216 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-472161 SN - 2046-1402 N1 - Copyright: © 2017 Seo H et al. This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Data associated with the article are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication). VL - 5 IS - 1945 SP - 1 EP - 24 PB - F1000 Research Ltd CY - London ER -