Evaluation of seed-based MC.

(A) Correlation matrix indicating whole-brain FC (beneath diagonal) and MC (above diagonal). Correlations not surviving significance testing 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 is considered as indicative of small-world properties). Copmarison of (D) FC and (G) MC early (20-40 minutes after scan start, below diagonal) and late (60-80 minutes after scan start, above diagonal). The similarties of early and late readouts were quantified for both (E) FC and (H) MC. 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 scan start. Abbreviations: FC = fMRI-derived hemodynamic functional connectivity, MC = [11C]DASB PET-derived molecular connectivity.

Group independent component analysis for FC and MC.

(A) ICA 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 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 SERT network, defined by IC 1 in validation cohort. Right panel: Dynamic binding potentials of regions comprising salience network, defined by IC 1 in validation cohort. (B) Overlap between independent components extracted from the validation cohort (IC 1 = SERT network; IC 2 = salience network) and the early and late effects of MDMA respectively. (C) Pair-wise correlations between regional z-scores of the ICs extracted from validation cohort and regional t-scores of early and late MDMA effects. (*** indicates p < 0.001, ns = non-significant). Abbreviations: SERT = serotonin transporter, ICA = independent component analysis; for abbreviations of regions please refer to Supplementary Information).

Comparison of MC and BPND changes.

A Reductions in BPND following MDMA (orange) and MC strength (blue) were compared. B T-scores derived from each approach show only low correlations.

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

(A) FC and (C) MC brain networks depicting edge and node strengths of the salience network and SERT network at baseline (20-40 min after scan start) and after MDMA (60-80 min after scan start). (B) FC and (D) MC time-resolved salience and SERT network strengths computed using sliding windows. Asterisks indicate significant (p < 0.05, FDR-corrected) changes to baseline (time-point zero, corresponding to 20-40 minutes after scan start). Abbreviations: SN = salience network, SERT = SERT network.