80 1,000 Hz intermixed pseudorandomly with 10% pitch- deviant (50 ms at 1,200 Hz) and 10% duration-deviant (100 ms at 1,000 Hz) stimuli. During the recording of the EEG, subjects performed a visual AX-continuous performance task (AX-CPT), which distracted their attention from the acoustic stimuli. The AX- CPT requires the subjects to press a button, whenever the letter X follows the letter A. Whenever a letter different than A is presented prior to X (“BX”) the subject has to inhibit the tendency to respond to it. It is interesting to note that schizophrenic patients commit more BX errors, suggesting a deficient use of contextual information in this task (Cohen et al. 1999; Javitt et al. 2000; Umbricht et al. 2003a, b). Therefore, the influence of the two drugs on the utilization of contextual information in this AX-CPT was also an object of our study. The visual AX-CPT was programmed using the presen- tation software (Neurobehavioral Systems, Albany, USA) according to Umbricht et al. (2000): Single letters were presented for 250 ms visually on a computer screen, which was positioned in front of the subject. The instruction was to press a button whenever the letter A (correct cue) was followed by the letter X (correct target), “AX.” The three other orders (correct cue–incorrect target “AY,” incorrect cue–correct target “BX,” and incorrect cue–incorrect target “BY”) had to be ignored. Incorrect cues and targets consisted of all letters other than A or X. Fifty percent of the cue–target sequences were presented pseudorandomly intermixed with a short ISI of 0.8 s and the remaining 50% with a long ISI of 4 s. The time between stimulus pairs was constant at 0.8 s. The correct cue–target sequence (A–X) occurred with a probability of 70% and the three other orders with a probability of 10% each. Data analysis MMN and N1 Digital tags were logged to all auditory stimuli, and the continuous data were divided on the basis of these tags into 600-ms epochs (100 ms pre- and 500 ms poststimulus). Parallel to the EEG, we registered two EOG channels, one for vertical and one for horizontal eye movements. If there was an eye movement registered in either EOG channel, the contemporaneous EEG epoch was rejected. After correction for blinks, epochs with amplitudes exceeding ±80 μV were also rejected offline during the averaging procedure (BESA 2000 software, MEGIS, Munich, Germany). Grand averages were built separately for the standard and the two deviant stimuli. Data were digitally filtered using a 30-Hz low-pass and a 1-Hz high-pass (12 dB) filter. After averaging and artifact rejection, the MMN waveform was calculated sepa- rately for each subject and each condition (baseline, DMT Psychopharmacology (2008) 199:77–88 moderate/high, S-ketamine moderate/high) by subtracting the standard waveform from the deviant (frequency-respective duration) waveform using the BESA software. In a first step, we assessed the peak MMN amplitude by using the MMN waveforms from the surface electrodes Fz, F3, and F4. The peak negativity within a latency window of 100–200 ms poststimulus for the frequency deviant and 150–250 ms for the duration deviant in the corresponding surface waveforms was defined as the MMN peak amplitude. The effects of the two drugs on the MMN peak amplitude were analyzed separately for the duration and the frequency deviants by means of a repeated-measures analysis of variance (ANOVA) using the position of the electrode as a within-subject factor. Initially, we performed analyses of variance for each of the two drugs with the factor condition (baseline, low dose, high dose). Then, to directly compare the two drugs with each other, we performed ANOVAs with the factors drug (DMT, S-ketamine) and dosage (low, high). Post-hoc least-square difference (LSD) tests were performed if indicated. In a second step, individual electrode positions from all nine subjects were matched to a common head model to perform the source analysis of the MMN. A source analysis was performed individually for each subject, deviant stimulus, and drug condition with the BESA software on the basis of the four generators model of MMN as described by Waberski et al. (2001). Figure 1 displays the location of the four sources: S1 right superior temporal lobe, S2 left superior temporal lobe, S3 right inferior temporal lobe, and S4 anterior cingulate gyrus. The Talairach coordinates for the sources are presented in Table 1. The peak values of the MMN amplitude were determined at each source in a time window of 100–200 ms poststimulus for the frequency deviant and 150–250 ms for the duration deviant in the corresponding source waveforms. In addition to the MMN, we assessed the N1 amplitude by using the waveforms generated by the standard stimulus at electrode Fz. The peak negativity within a latency window of 50 to 150 ms poststimulus was defined as the N1 amplitude. The N1 peak amplitudes were measured to ensure that MMN deficits under the drug conditions are not only caused by a general reduction in EEG activity. We analyzed the effects of the two drugs on the MMN amplitude separately for the duration and the frequency deviants and for each source by means of ANOVAs. Initially, we performed ANOVAs for each of the two drugs with the factor condition (baseline, low dose, high dose). Then, we performed ANOVAs with the factors drug (DMT, S-ketamine) and dosage (low, high). Post-hoc LSD tests were performed if indicated. Similarly, the amplitude and latency of the N1 to the standard stimulus were analyzed by means of ANOVAs, first separately for each drug with the factor condition and then without the baseline data using the factors drug and dosage.