Resting-state functional connectivity in naturalistic psychedelic users

Abstract

This is an amendment to the preregistration by Orłowski et al. (2024; OSF: https://doi.org/10.17605/OSF.IO/CQUJR), which was submitted for the full Orłowski et al. (2025, Human Brain Mapping) study. The original preregistration included a brief plan for resting-state functional connectivity (rs-FC) analysis in experienced psychedelic users (N = 33; ≥ 10 lifetime experiences, ≥ 30 days abstinence) compared to matched non-users (N = 34). This amendment fully operationalises those hypotheses and adds one new confirmatory hypothesis motivated by a mega-analysis published after the original submission (Girn et al., 2026, Nature Medicine). The resting-state fMRI data (10 min, 500 volumes; 3T Siemens Prisma; preprocessed with fMRIPrep 24.0.1) have not been analysed at the time of this registration — no functional connectivity matrices, seed-based maps, or group comparisons have been computed. Confirmatory hypotheses (H1–H4): - H1: Within-DMN functional connectivity (Schaefer 200, 17-network; mPFC–PCC seed pair) - H2: DMN-anchored between-network FC (DMN–CON, DMN–SN) - H3: Seed-based FC of five emotional-processing regions (bilateral amygdala, dACC, DLPFC, mPFC, PCC) - H4 (new): Subcortical seed-based FC — caudate, putamen, and thalamus to sensorimotor cortex, motivated by Girn et al. (2026) All confirmatory tests include Cohen's d, 95% CI, Bayes factors (JZS prior), and TOST equivalence testing (SESOI d = 0.5). Six exploratory analyses (E1–E6) are additionally pre-specified, including graph-theoretic measures, brain–behaviour associations, and thalamic nuclei specificity.

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