Exploring subacute effects of a DMT and harmine meditation retreat on the brain's control energy landscape
Modeling the brain as a controllable structural network allows the estimation of the control energy (CE) required to reach functional states, where low-CE states are more accessible. Psychedelics are thought to acutely flatten the brain's CE landscape, broadening the repertoire of reachable states, but whether this reorganization persists into the subacute ``afterglow" window is largely unknown. This exploratory study uses rs-fMRI from a randomized, double-blind, placebo-controlled trial (N = 39; 19 verum [N,N-dimethyltryptamine (DMT) + harmine, Ayahuasca-inspired formulation], 20 placebo) scanned before and after a three-day meditation retreat. We compute CE on a group human connectome project (HCP) structural connectome under two approaches that emphasize long and short timescale dynamics. Globally, we found no systematic shift in the distribution of CE between transitions, however mean CE increased in both groups at the long timescale approach. Surviving network effects emerge when a network's intrinsic timescale matches the stabilization regime. In the long timescale regime, the central executive network (CEN) showed an increase in post-retreat CE within the verum group that survived Benjamini-Hochberg False Discovery Rate (FDR-BH) correction. Although CE and functional connectivity are distinct, this higher CEN cost may relate to the reduced within-network connectivity previously reported subacutely after psilocybin. The default mode network (DMN) also showed a post-retreat CE increase in both groups, but neither change survived FDR correction. In the short timescale approach, the visual network (VN) showed a FDR-BH CE decrease within the verum group, consistent with reduced dynamical demand in a region acutely engaged by DMT. To examine whether changes were concentrated in less accessible states, we additionally analyzed rare brain states, defined by the top decile of information content. This analysis revealed a modest session x condition interaction in the long timescale approach. Overall, the two timescale lenses surface different network effects, that align with cortical timescale hierarchies. These findings point to network- and timescale-specific, rather than global, CE changes in the afterglow window, though effects are small and heterogeneous and require confirmation in larger samples. Characterizing whether and where psychedelic effects persist into the subacute window is relevant to psychedelic-assisted therapy, including safety, therapeutic timing, and durability of drug effects. More broadly, considering cortical timescale hierarchies may help identify network-specific CE changes that might be less apparent when networks are evaluated under a single dynamical timescale.