General indices to characterize the electrical response of the cerebral cortex to TMS

Transcranial magnetic stimulation (TMS) combined with simultaneous high-density electroencephalography (hd-EEG) represents a straightforward way to gauge cortical excitability and connectivity in humans. However, the analysis, classification and interpretation of TMS-evoked potentials are hampered by scarce a priori knowledge about the physiological effect of TMS and by lack of an established data analysis framework. Here, we implemented a standardized, data-driven procedure to characterize the electrical response of the cerebral cortex to TMS by means of three synthetic indices: significant current density (SCD), phase-locking (PL) and significant current scattering (SCS). SCD sums up the amplitude of all significant currents induced by TMS, PL reflects the ability of TMS to reset the phase of ongoing cortical oscillations, while SCS measures the average distance of significantly activated sources from the site of stimulation. These indices are aimed at capturing different aspects of brain responsiveness, ranging from global cortical excitability towards global cortical connectivity. We analyzed the EEG responses to TMS of Brodmann's area 19 at increasing intensities in five healthy subjects. The spatial distribution and time course of SCD, PL and SCS revealed a reproducible profile of excitability and connectivity, characterized by a local activation threshold around a TMS-induced electric field of 50 V/m and by a selective propagation of TMS-evoked activation from occipital to ipsilateral frontal areas that reached a maximum at 70-100 ms. These general indices may be used to characterize the effects of TMS on any cortical area and to quantitatively evaluate cortical excitability and connectivity in physiological and pathological conditions.