Objective Incorporating high-frequency components in transcutaneous electrical stimulation (TES) waveforms may make it possible to stimulate deeper nerve fibers since the impedance of tissue declines with increasing frequency. carrier modulated by a square-pulse train. Main results The model revealed that high-frequency signals generated larger potentials at depth than did low frequencies but this did not translate into lower activation thresholds. Both TAMS and standard rectangular pulses activated more superficial fibers in addition to the deeper target fibers and at no frequency PF 670462 did we observe an inversion of the strength-distance relationship. Current regulated activation was more strongly influenced by fiber depth whereas voltage regulated activation was more strongly influenced by skin thickness. Finally our model reproduced the threshold-frequency relationship of experimentally measured motor thresholds. Significance The model may be used for prediction of motor thresholds in TES and contributes to the understanding of high-frequency TES. 2009 The use of high frequency waveforms for TES is usually suggested by the reduced impedance of the skin with increasing frequency (Rosell 1988). Thus it may be PF 670462 possible to reach deeper structures by adding high frequency components to the activation waveform. Specifically a transcutaneous amplitude modulated transmission (TAMS) in which a high frequency (210 kHz) sinusoidal carrier is usually modulated by a traditional rectangular pulse was proposed as a non-invasive neurostimulation approach that can modulate bladder activity similarly to direct PF 670462 pudendal nerve activation (Shen 2011 Tai 2012). However the mechanisms of actions of TAMS which may differ substantially from standard low-frequency activation remain largely unexplored. The potentials generated in the tissue by an electrode in contact with the skin are dependent on the electrical properties of the electrode-tissue interface and tissue and the geometry of the electrode and tissue. In the frequency range commonly used for peripheral nerve activation tissues are considered as purely resistive and capacitive inductive and propagation effects are neglected through the quasi-static assumption (Plonsey and Heppner 1967). Under certain conditions however these simplifications may not be appropriate (Bossetti 2008) particularly in cases where the frequency content of the signal extends Mouse monoclonal to SMAD5 to the kHz range. In this study we present a model of TES in which we calculate the distribution of potentials without invoking the quasi-static assumption. Although in the past many studies have used volume conductor models to estimate the potentials generated during TES only a few have considered transcutaneous activation in the kHz range without relying on the quasi-static assumption (Kuhn 2009 Hartinger 2010 PF 670462 Mesin and Merletti 2008). We implemented a two-step model (McNeal 1976) of TES using a distributed parameter volume conductor model to quantify the spatiotemporal distribution of potentials in the tissue and a cable model of a mammalian myelinated axon to quantify excitation of peripheral nerve fibers. Our objective was to determine whether the introduction of high frequency components up to hundreds of kHz made it possible to reach deeper structures thereby facilitating nerve fiber excitation. The results contribute to understanding the mechanisms of TES with novel high frequency waveforms such as TAMS. 2 Methods 2.1 Volume conductor model We calculated the potentials in a volume conductor consisting of three planar layers of tissue with frequency-dependent dielectric properties (figure 1). We applied voltage PF 670462 or current source activation on the most superficial layer including a model of the electrode-skin interface impedance. The potential in the modeled tissue �� is explained by the inhomogeneous PF 670462 Helmholtz equation (for any derivation of this equation see for example Bossetti (2008)) which is expressed in the frequency domain name as: and space variables into the spatial frequencies and is the potential in the transformed domain and are the thicknesses of the skin and excess fat layer respectively 1996 The solution of (2) is usually written as: and are dependent on the boundary conditions 2008 Grant and Lowery 2010). Assuming that all current.