Spatiotemporal Dynamics of Single and Paired Pulse TMS-EEG Responses

For physiological brain function a particular balance between excitation and inhibition is essential. Paired pulse transcranial magnetic stimulation (TMS) can estimate cortical excitability and the relative contribution of inhibitory and excitatory networks. Combining TMS with electroencephalography (EEG) enables additional assessment of the spatiotemporal dynamics of neuronal responses in the stimulated brain. This study aims to evaluate the spatiotemporal dynamics and stability of single and paired pulse TMS-EEG responses, and assess long intracortical inhibition (LICI) at the cortical level. Twenty-five healthy subjects were studied twice, approximately one week apart. Manual coil positioning was applied in sixteen subjects and robot-guided positioning in nine. Both motor cortices were stimulated with 50 single pulses and 50 paired pulses at each of the five interstimulus intervals (ISIs): 100, 150, 200, 250 and 300 ms. To assess stability and LICI, the intraclass correlation coefficient and cluster-based permutation analysis were used. We found great resemblance in the topographical distribution of the characteristic TMS-EEG components for single and paired pulse TMS. Stimulation of the dominant and non-dominant hemisphere resulted in a mirrored spatiotemporal dynamics. No significant effect on the TMS-EEG responses was found for either stimulated hemisphere, time or coil positioning method, indicating the stability of both single and paired pulse TMS-EEG responses. For all ISIs, LICI was characterized by significant suppression of the late N100 and P180 components in the central areas, without affecting the early P30, N45 and P60 components. These observations in healthy subjects can serve as reference values for future neuropsychiatric and pharmacological studies.