Combining Transcranial Magnetic Stimulation with Electroencephalography to Study Human Cortical Excitability and Effective Connectivity Mario Rosanova, Silvia Casarotto, Andrea Pigorini, Paola Canali, Adenauer G. Casali, and Marcello Massimini Abstract Excitability and effective connectivity are key parameters of cortical circuits’ functioning. Moreover, alterations of these parameters have been suggested to underlie neurologic and psychiatric conditions. Transcranial Magnetic Stimulation (TMS) combined with neuronavigation systems, electroencephalogra- phy (EEG), and reliable reconstruction of cortical generators allows to directly measure cortical excit- ability and effective connectivity, noninvasively and with the appropriate temporal resolution (milliseconds). Here, the main technical challenges that have to be dealt with to efficiently combine navigated TMS with EEG on human subjects and a step-by-step experimental procedure to perform a successful TMS/EEG measurement are presented. Finally, ad hoc analytical tools to extract indices of excitability and effective connectivity from TMS/EEG data are described together with examples of their application. Key words: TMS/EEG, Neuronavigation, Cortical circuits, Perturbation, Noninvasive 1. Introduction The human cerebral cortex is composed of several specialized regions that communicate by means of short-range and long- range bundles of axons. Corticocortical interactions occur on a subsecond timescale (hundreds of milliseconds) and allow the cerebral cortex, for instance, to rapidly integrate information across different sensory modalities and submodalities, to orient the focus of visual attention, to maintain objects’ representations in the visual working memory, to retrieve memories and, more generally, to generate conscious experiences. Moreover, physiological and pathological alterations of the excitability and effective connectivity within cortical circuits have been suggested to underlie deep sleep, anesthesia and the most common 435 Neuromethods (2012) 67: 435–457 DOI 10.1007/7657_2011_15 © Springer Science+Business Media, LLC 2011 Published online: 27 November 2011