This thesis, consisting of seven original publications (I-VII), explored the technical and neurophysiological plausibility of combining neuro-navigated transcranial magnetic stimulation (nTMS) with neuroimaging techniques such as multichannel electroencephalography (EEG) and magnetoencephalography (MEG). This work has focused on the interaction between the current state of neuronal activity at the targeted cortical network and the effects of TMS. We took an interactive approach, including a correlation betweeen cortical (EEG, MEG) vs. peripheral electromyographic (EMG) measurements. TMS-evoked EEG responses were used as probes for current functional state of the cortex during the processing of sensory stimuli and the preparation/execution of different motor activities. Contrary to standard indirect approaches utilizing peripheral EMG measures, our study directly demonstrated graded excitability in contra- and ipsilateral hemispheres during the preparation/execution of unilateral movements. The obtained data suggest that the specific balance of interhemispehric excitability is tailored for the optimal performance of unilateral movement by preventing not only mirror movements through decreased excitability of ipsilateral hemispehre, but also via pre-emptive background tonic inhibition of this hemisphere. The utility of the TMS-EEG combination was further demonstrated by providing direct evidence for cortical involvement in short-latency afferent inhibition. We found a linear correlation between the attenuation of TMS-evoked EEG responses and the attenuation of muscle responses, thus revealing how changes in cortical neuronal activity are related to changes on the periphery. The clinical feasibility of the TMS-MEG combination was demonstrated by showing that delivering trains of TMS pulses to the motor cortex of Parkinson's patients successfully modulated the spontaneous beta-range oscillations measured with MEG over the rolandic cortical regions, suggesting probable alteration of the cortico-thalamo-basal ganglia networks. The present thesis demonstrates that the spatial accuracy of localizing primary motor representational areas with both MEG and nTMS in superior to electrical cortical stimulation via subdural grids. Furthermore, this work demonstrates very high reproducibility of TMS-evoked EEG deflections after repeated stimulation of both the primary motor and prefrontal cortices. This suggests new standards in preoperative clinical workup and a wide range studies with test-retest design. Thus, this thesis provides a new methodological and technical framework for measuring the time-resolved functional connectivity and causality of activation in the observed neural networks of human cerebral cortex
