Multitrodes

Subjects were seated with eyes open while fixating. During stimulation subjects listened to a colored masking noise18 whose intensity was adjusted individually in each experimental session, until the participant reported that they were unable to hear the TMS‐click. TMS‐compatible EEG equipment (BrainAmp MRplus, BrainProducts GmbH) with a 64‐electrode cap (Multitrodes, BrainCap‐Fast'n Easy) was used. 150 consecutive TMS stimuli, with inter‐trial interval of approximately 4 sec (random variation of 20%), were applied at 100% RMT. RMT was obtained before and at 2, 4, and 6 h after drug administration. In each TMS‐EEG session the stimulation intensity was kept relative to the predrug RMT. PK blood samples were obtained ~5 min before each postdose TMS measurement period.

The EEG was recorded using 32 scalp electrodes placed in an elastic headcap at the locations of the International 10–20 system. The electrodes have been designed specifically for the combination of EEG with TMS (Multitrodes, Brain Products GmBH, Germany). Their very flat profile allows minimizing the distance between the TMS coil and the scalp surface. Most importantly, orientation of the lead wires can be freely adjusted. This allowed positioning the wires orthogonal relative to the coil handle and then to adjust their position such as to reduce TMS-induced artifacts [21 ]. Finally, a thin plastic foil was wrapped around the electrode cap to reduce artifacts related to contact between the coil and the electrodes. Once impedances below 5 kΩ were ensured, the signals were amplified and digitized at 2 kHz using an Asalab HS64 EEG system (ANT Neuro, Enschede, NL). The ground electrode was positioned at AFz. A common average served as the active reference. Two electrodes placed at the upper-left and lower-right sides of the right eye were used to monitor ocular movements and eye blink artifacts.