Evaluation of the seed-based MC.

(A) Correlation matrix indicating whole-brain FC (beneath the diagonal) and MC (above the diagonal). Correlations not significant with multiple comparison corrections were set to zero (p < 0.05, FWE correction). (B) Scatter plot and correlation between MC and FC edges. (C) Small-world coefficients for all subjects and group-level one-sample t-test against the value of 1 (SW > 1 indicates small-world properties). Comparison of (D) FC and (G) MC early (20-40 minutes after the start of the scan, below the diagonal) and late (60-80 minutes after the start of the scan, above the diagonal). The similarities of early and late readouts were quantified for both (E) FC and (H) MC. The temporal stability of both (F) FC and (I) MC was evaluated using a sliding window approach, including 20-minute windows between 20 and 80 minutes after the start of the scan. Abbreviations: FC = fMRI-derived hemodynamic functional connectivity, MC = [11C]DASB PET-derived molecular connectivity.

Group independent component analysis for FC and MC.

(A) ICA was performed over 10 components for fMRI. (B) ICA performed over 2 components for [11C]DASB PET and regional quantification of the two derived components. The ICA was repeated over 10 components. Four and three components showed good overlap with the two components defined above. All the components were thresholded at z > 1.96 (p ≤ 0.05). Abbreviations: FC = fMRI-derived hemodynamic functional connectivity, MC = [11C]DASB PET-derived molecular connectivity.

Comparison of MDMA-induced [11C]DASB alterations.

(A) Left panel: Dynamic binding potentials of regions comprising the SERT subcortical network, defined by IC 1 in the validation cohort. Right panel: Dynamic binding potentials of regions comprising the SERT salience network, defined by IC 2 in the validation cohort (continuous lines indicate the means, and dotted lines indicate standard deviations). (B) Overlap between independent components extracted from the validation cohort (IC 1 = SERT subcortical network, IC 2 = SERT salience network;) and the early and late effects of MDMA. (C) Pairwise correlations between regional z scores of the ICs extracted from the validation cohort and regional t scores of early and late MDMA effects. (*** indicates p < 0.001, ns = nonsignificant). Abbreviations: SERT = serotonin transporter, ICA = independent component analysis; for abbreviations of regions, please refer to the Supplementary Information).

Comparison of MC and BPND changes following MDMA.

A Reductions in BPND following MDMA (orange) and MC strength (blue) were compared. B The correlation coefficient of the regional T scores was low (r = 0.29).

MDMA effects on seed-based FC and MC of the salience and subcortical networks.

(A) FC and (C) MC brain networks depicting the edge and node strengths of the salience network and subcortical network at baseline (20-40 min after the start of the scan) and after MDMA (60-80 min after the start of the scan). (B) FC and (D) MC time-resolved salience and subcortical network strengths computed by sliding windows. Individual values are provided in the bar graphs for the baseline and final post-MDMA periods. Asterisks indicate significant (p < 0.05, FDR-corrected) changes from baseline (time point zero, corresponding to 20–40 minutes after the start of the scan).