title: Cortical neuron activation induced by electromagnetic stimulation: a quantitative analysis via modelling and simulation.
abstract: Previous simulation works concerned with the mechanism of non-invasive neuromodulation has isolated many of the factors that can influence stimulation potency, but an inclusive account of the interplay between these factors on realistic neurons is still lacking. To give a comprehensive investigation on the stimulation-evoked neuronal activation, we developed a simulation scheme which incorporates highly detailed physiological and morphological properties of pyramidal cells. The model was implemented on a multitude of neurons; their thresholds and corresponding activation points with respect to various field directions and pulse waveforms were recorded. The results showed that the simulated thresholds had a minor anisotropy and reached minimum when the field direction was parallel to the dendritic-somatic axis; the layer 5 pyramidal cells always had lower thresholds but substantial variances were also observed within layers; reducing pulse length could magnify the threshold values as well as the variance; tortuosity and arborization of axonal segments could obstruct action potential initiation. The dependence of the initiation sites on both the orientation and the duration of the stimulus implies that the cellular excitability might represent the result of the competition between various firing-capable axonal components, each with a unique susceptibility determined by the local geometry. Moreover, the measurements obtained in simulation intimately resemble recordings in physiological and clinical studies, which seems to suggest that, with minimum simplification of the neuron model, the cable theory-based simulation approach can have sufficient verisimilitude to give quantitatively accurate evaluation of cell activities in response to the externally applied field.
authors.affiliation: Neuroengineering Laboratory, National University of Singapore, Block EA #04-25, 9 Engineering Drive 1, Singapore, 117576, Singapore.
authors.forename: Tiecheng
authors.initials: T
authors.lastname: Wu
authors.affiliation: Neuroengineering Laboratory, National University of Singapore, Block EA #04-25, 9 Engineering Drive 1, Singapore, 117576, Singapore.|Newrocare Pte Ltd, 6 Eu Tong Sen Street, #12-03, SohoCentral Singapore, 059817, Singapore.
authors.forename: Jie
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Mechanical Engineering, National University of Singapore, Singapore, Singapore.
authors.forename: Kim Seng
authors.initials: KS
authors.lastname: Lee
authors.affiliation: Neuroengineering Laboratory, National University of Singapore, Block EA #04-25, 9 Engineering Drive 1, Singapore, 117576, Singapore. mpelixp@nus.edu.sg.
authors.forename: Xiaoping
authors.identifier: http://orcid.org/0000-0001-7975-366X
authors.initials: X
authors.lastname: Li
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000528:radiation effects; D002540:Cerebral Cortex / Q000166:cytology*; D003198:Computer Simulation; D004558:Electric Stimulation; D055590:Electromagnetic Phenomena; D008959:Models, Neurological; D009474:Neurons / Q000528:radiation effects* / Q000648:ultrastructure; D017711:Nonlinear Dynamics
keywords: Action potential initiation point; Computer simulation; Neuromodulation; Pyramidal cell; Stimulation threshold