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Perhaps a limitation to our study however, we used single pulse TMS having inter-trial intervals?Tariquidar exclude the possibility that short-term plasticity may have influenced some of our observations. As fundamental properties of brain circuitry any such short-term physiological plasticity would likely be due to conventional synaptic mechanisms, such as receptor saturation, receptor trafficking, changes in channel gating kinetics, synaptic vesicle pool depletion, and dynamic regulation of neurotransmitter release probability, which have all been well-studied at corticocortical and corticothalamic synapses between pyramidal neurons, interneurons, and thalamic relay neurons (Sanes and Donoghue, 2000, Thomson, 2003?and?Zucker and Regehr, 2002). It is nearly impossible to determine which, if any, of these aforementioned mechanisms may have contributed to the trial-to-trial MEP variability we observed since it is not known with any certainty to what degree specific neuronal elements are affected by the electric field induced by TMS. Future GSK3B studies should however begin driving towards using high-resolution modeling to investigate how different time components of electric fields mediate physiological outcomes (including plasticity) induced by TMS across different timescales. This is a difficult but important and seemingly tractable SAHA HDAC concentration problem if simulations can include faithful models of neuronal and synaptic populations which react differently to time varying pulse shapes and sequences. Such studies should shed light on the temporal behavior of TMS-induced electric fields while more accurately detailing the mechanisms of action across different embodiments of TMS. One of the main objectives of the present study was to compare and contrast neurophysiological observations with the results from FEM simulations of TMS-induced electric fields. Comparisons of TMS CoG with the fMRI BOLD CoG have been recently reported (Diekhoff et al., 2011). Using similar approaches we found fMRI BOLD signals in response to voluntary index finger movement to be localized to primary motor and, of course, premotor and supplementary motor cortex. Comparing the fMRI BOLD CoG with the TMS-induced electric field center of gravity (Ecog), we found that the TMS-induced electric fields were concentrated on the primary motor cortex, as well as surrounding gyri during motormapping. Further, we found the normal component of the modeled electric field in these regions to be correlated with the amplitudes of TMS-elicited MEPs ( Fig.?8A).