Data analysis
TRD
SECONDARY
Seed-to-whole-brain rsFC analyses were performed using AFNI (v 22.3.07) [Linear-mixed effects models (3dLMEr [group is a between-subject factor with two levels (TRD, HV);treatment is a within-subject factor with two levels (ketamine, placebo);region is a within-subject factor with three levels (sgACC, pgACC, dACC);group × treatment × region is the interaction between these three factors;order is a between-subject factor with two levels (subject’s infusion order; ketamine first or second); and(1|subject), (1|subject:treatment) and (1|subject:region) are a random effects within subjects.Results of the main interaction effect (group × treatment × region) are reported as a chi-square (χregion-specific group × treatment interactions separately for sgACC, pgACC and dACC;region-specific effects of treatment within the TRD group alone;effects of region alone, to demonstrate expected patterns of seed-whole brain rsFC; andgroup × order interaction to explore the possibility of differential expectancy and carry-over effects between the groups.A cluster-forming threshold of To correlate changes in connectivity with changes in symptom scores, significant clusters for the main group × treatment × region interaction, and clusters for the effect of treatment within the TRD group alone, were correlated with changes in MADRS, SHAPS and TEPS-anticipatory/TEPS-consummatory scores. Differences (ketamine – placebo) in MADRS, SHAPS and TEPS-anticipatory/TEPS-consummatory scores at day two post-infusion were correlated with changes in rsFC (ketamine – placebo) at day two post-infusion. Pearson correlation coefficients were calculated, and statistical significance was assessed at Post-hoc correlation of significant clusters with symptom improvements has associated bias as described in ref. [Post-hoc general linear No a priori power analysis was performed because the present study was a secondary analysis of a clinical trial [