Johnson JS, Kundu B, Casali AG, Postle BR. Task-dependent changes in cortical excitability and effective connectivity: a combined TMS-EEG study. J Neurophysiol 107: 2383-2392, 2012. First published February 8, 2012 doi:10.1152/jn.00707.2011.-The brain's electrical response to transcranial magnetic stimulation (TMS) is known to be influenced by exogenous factors such as the frequency and intensity of stimulation and the orientation and positioning of the stimulating coil. Less understood, however, is the influence of endogenous neural factors, such as global brain state, on the TMS-evoked response (TMS-ER). In the present study, we explored how changes in behavioral state affect the TMS-ER by perturbing the superior parietal lobule (SPL) with single pulses of TMS and measuring consequent differences in the frequency, strength, and spatial spread of TMS-evoked currents during the delay period of a spatial shortterm memory task and during a period of passive fixation. Results revealed that task performance increased the overall strength of electrical currents induced by TMS, increased the spatial spread of TMS-evoked activity to distal brain regions, and increased the ability of TMS to reset the phase of ongoing broadband cortical oscillations. By contrast, task performance had little effect on the dominant frequency of the TMS-ER, both locally and at distal brain areas. These findings contribute to a growing body of work using combined TMS and neuroimaging methods to explore task-dependent changes in the functional organization of cortical networks implicated in task performance.electroencephalography; transcranial magnetic stimulation TRANSCRANIAL MAGNETIC STIMULATION (TMS) is a method that exploits the principle of electromagnetic induction to noninvasively stimulate specific brain areas with the goal of testing hypotheses about brain-behavior relations (Walsh and PascualLeone 2003). Although numerous studies have revealed TMSinduced effects on behavioral performance, the endogenous neural factors linking TMS to behavior are at present poorly understood. An important goal of work in this area, therefore, is to uncover the factors that underlie observed variability in the effects of TMS on the brain and behavior. In the present study, we explored the influence of behavioral state on spectral and temporal properties of the TMS-evoked response (TMS-ER). The brain's response to TMS is known to be influenced by a number of factors specific to particular TMS protocols, including coil orientation (Bonato et al. 2006;Thut et al. 2011) and the intensity and frequency of stimulation (Komssi et al. 2004). Additionally, although the biophysical principles underlying TMS-related current induction are presumably the same for all neural tissue (Walsh and Pascual-Leone 2003), the effect of TMS on brain activity has been found to vary systematically as a function of where on the scalp it is applied. Notably, using combined TMS and electroencephalography (EEG), Rosanova and colleagues (2009) found that single pulses of TMS elicit...