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Objective  Long-interval cortical inhibition (LICI) can be recorded from motor and non-motor regions of the cortex through combined transcranial magnetic stimulation (TMS) with electroencephalography (EEG). This study aimed to evaluate additional dimensions of LICI characteristics over an extended time-frequency and spatial domain. This was done by introducing two alternative measures of LICI signal amplitude: the Discrete Fourier Transform (DFT) and the Hilbert transform (HT). Both approaches estimate signal amplitude not taking into account the phase. In both cases LICI was measured as the difference between the unconditioned and conditioned activity evoked by the test pulse. Finally, we evaluated whether the topographical patterns of single and paired responses differed beyond the expected variations in amplitude.    Materials and Methods  LICI was delivered as single and paired pulses to the motor cortex (MC) and dorsolateral prefrontal cortex (DLPFC) in 33 healthy subjects with TMS-EEG.    Results  Significant differences (p<0.0001) between the unconditioned and conditioned evoked activity were found for both the DLPFC and MC using both methods (i.e., DFT and HT) after correcting for multiple comparisons in the time-frequency domain. The influence of inhibition was found to be significantly larger in space and time than previously considered. Single and paired conditions differ in intensity, but also in their topographic pattern (i.e., the specific spatiotemporal configuration of active sources).    Conclusion  Similar results were found by both DFT and HT. The effect of inhibition across the cortex was also found to be complex and extended. In particular, it was found that LICI may be measured with high sensitivity in areas that were relatively distant from the stimulation site, which may have important practical applications. The analysis presented in this study overcomes some limitations of previous studies and could serve as a key reference for future studies examining TMS-indices of inhibition/excitation in healthy and diseased states.

Characterizing Long Interval Cortical Inhibition over the Time-Frequency Domain