fMRI data analysis
REGRESSION
For each participant, a fixed-effects general linear model (GLM) was fitted to the preprocessed BOLD signal data using SPM12. The GLM contained separate sets of four regressors for the social and physical trials, modeling the following trial parts: presentation of the question before and after the video, presentation of the video, response, and confidence rating. The model further included six movement regressors representing estimates of rotation and translation created during the realignment step of data preprocessing, and a constant term. While the task was not designed to separate neural activation evoked during the subsequent trial parts, modeling these trial parts separately increased the flexibility of the GLM at small costs on degrees of freedom. The response phase was modelled from offset of the second question presentation to participants’ answer to the mentalizing question, and the confidence rating phase spanned the time between answer to the mentalizing question and locking of the confidence rating. Regression coefficients (parameter estimates) for these regressors were estimated for each voxel of each participant’s brain. Linear contrasts were applied to the individual parameter estimates of the response to the experimental conditions in order to contrast each of these four trial parts of the social and physical trials.To determine the effect of ketamine on BOLD signal during mentalizing, we first verified that the social cognition task evoked activation in brain regions known to be involved in social cognition under placebo. To this end, we constructed a second-level (random effects) model in SPM that allowed us to contrast neural correlates of social vs non-social cognition under placebo and ketamine in the four trial parts (see Fig. Parameter estimates from a region of interest (ROI) in the right pSTS region, identified in one of the t-tests (see Results), were exported using MarsBaR in SPM12Effects of ketamine on functional connectivity between the pSTS ROI and other areas of the brain were assessed using a generalized psychophysiological interactions (gPPI) analysis with the CONN-toolbox in SPM 12Contrast images between functional connectivity during the social and physical question part of the trial (SOC > PHY) were then separately assessed in the participants of the placebo and the ketamine group using random effects one-sample t-tests in SPM 12; the effect of ketamine was assessed by comparing these contrast maps across groups using an independent samples t-test. All results of the fMRI analyses were considered significant if they exceeded the threshold of p < 0.05 after family-wise error correction for multiple comparisons at the cluster level across all the voxels of the brain, based on an uncorrected threshold (= cluster-forming threshold) of p < 0.001 at the voxel level. These results are indicated as p