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The excitation threshold of the human motor cortex (M1) was estimated on the basis of electroencephalographic (EEG) responses evoked by transcranial magnetic stimulation (TMS). The hand area of M1 (n = 7) was stimulated at ten intensities. The four dominant peaks of the overall brain response were reliably determined when stimulation intensity was  40% of the motor threshold, the probability of identifying each peak ranging between 0.71 and 0.86. Therefore, the cortical electric field of 33–44 mV/mm, approximately being induced with this intensity, may be estimated as the threshold for evoking measurable brain activity by motor-cortex TMS. As TMS–EEG enables the assessment of cortical reactivity with excellent sensitivity, it seems justified to move over to lower stimulation intensities, for increased safety.

Electroencephalographic (EEG) responses measured simultaneously with transcranial magnetic stimulation (TMS) have opened a new window into the human nervous system. The combined use of TMS and EEG (TMS-EEG) provides a means for the detailed study of the reactivity of any cortical region in the intact brain; also the reactivities of non-motor cortical areas related with higher-order functions are now appreciable. A recent epochal finding concerning cortical reactivity is that neuronal activation is induced with remarkably low stimulation intensities. This knowledge is significant when optimizing experimental set-ups for maximal patient safety. Stimulation of different cortical areas evokes different patterns of remote EEG activity, confirming the viability of TMS-EEG for the study of corticocortical connections. In this review, we expand on these and other notable findings related with TMS-EEG. We discuss the possibilities of the technique for the study of cortical reactivity and connectivity. We show that TMS-EEG allows the study of interhemispheric connections with high spatiotemporal specificity and the assessment of cortical reactivity with excellent sensitivity.

To better understand the neuronal effects of transcranial magnetic stimulation (TMS), we studied how the TMS-evoked brain responses depend on stimulation intensity. We measured electroencephalographic (EEG) responses to motor-cortex TMS, estimated the intensity dependence of the overall brain response, and compared it to a theoretical model for the intensity dependence of the TMS-evoked neuronal activity. Left and right motor cortices of seven volunteers were stimulated at intensities of 60, 80, 100, and 120% of the motor threshold (MT). A figure-of-eight coil (diameter of each loop 4 cm) was used for focal stimulation. EEG was recorded with 60 scalp electrodes. The intensity of 60% of MT was sufficient to produce a distinct global mean field amplitude (GMFA) waveform in all subjects. The GMFA, reflecting the overall brain response, was composed of four peaks, appearing at 15 +/- 5 msec (Peak I), 44 +/- 10 msec (II), 102 +/- 18 msec (III), and 185 +/- 13 msec (IV). The peak amplitudes depended nonlinearly on intensity. This nonlinearity was most pronounced for Peaks I and II, whose amplitudes appeared to sample the initial part of the sigmoid-shaped curve modeling the strength of TMS-evoked neuronal activity. Although the response amplitude increased with stimulus intensity, scalp distributions of the potential were relatively similar for the four intensities. The results imply that TMS is able to evoke measurable brain activity at low stimulus intensities, probably significantly below 60% of MT. The shape of the response-stimulus intensity curve may be an indicator of the activation state of the brain.