effect of TMS on motor cortex during epidural recordings from human patients with electrodes implanted in the spinal cord for treatment of chronic pain (see Di Lazzaro (2008) for review). These studies have demonstrated that the various TMS protocols all produce effects that are believed to be mediated primarily via trans-synaptic intracortical pathways, rather than by direct axonal activation. However, there continues to be significant uncertainty regarding the precise cellular mechanisms by which TMS exerts its effects. Furthermore, several studies have suggested that the effects of single pulses of TMS are significantly affected by the underlying pre-existing cortical state (Silvanto et al., 2008; Romei et al., 2008; Silvanto & Pascual-Leone, 2008; Sauseng et al., 2009; Thut et al., 2011). Consequently, the relationship between the local effects of TMS and the network changes that result remain almost entirely unknown. Despite this uncertainty, TMS continues to be used to probe and to alter cortical excitability in a variety of different experimental paradigms.
