Psychedelics disrupt hierarchical cortical propagations in the default mode network of humans and mice.
Adam R Pines, Xue Zhang, John Kochalka, Sam S Vesuna, Isaac V Kauvar, Divya Rajasekharan, Travis Rick Reneau, Teddy J. Akiki, Laura M Hack, Joshua S. Siegel, Leanne M Williams
Proceedings of the National Academy of Sciences June 16, 2026 DOI: 10.1073/pnas.2522000123 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Meta-analysis of four independent datasets Peer reviewed |
|---|---|
| Population | Humans and mice |
| Interventions | Methylenedioxymethamphetamine psilocybin lysergic acid diethylamide |
| Topics | Default mode network |
| Keywords | Cortical propagations Hierarchical processing Neuroimaging Psychedelics |
| Key findings | All tested psychedelics attenuate signal flow magnitude and bottom-up directionality within the default mode network. |
Abstract
Psychedelic drugs are poised to become mainstream treatments, yet we lack a circuit-level account of how they reshape brain activity. Emerging evidence suggests that multiple psychedelic compounds modulate activity in the brain's default mode network (DMN), often interpreted as either increased or decreased bottom-up hierarchical processing. Most imaging studies, however, quantify activity as if it were stationary, remaining agnostic to the ascending or descending movements of activity that defines hierarchical processing. Here, we adapt optical flow analyses to track frame-to-frame trajectories of DMN activity across four independent datasets (humans and mice; methylenedioxymethamphetamine, psilocybin, and lysergic acid diethylamide; nine drug-vs.-control contrasts). In functional magnetic resonance and calcium imaging, all psychedelics attenuate signal flow magnitude and bottom-up directionality within the DMN. Propagation attenuation is not attributable to data quality or previously documented effects of psychedelics and is uniquely associated with self-reported outcomes. This replicable and generalizable attenuation of bottom-up cortical propagations provides fundamental clarification of the effects of psychedelics on macroscale hierarchical processing.
Comparable studies
Other systematic reviews and meta-analyses on default mode network, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The wandering brain: Meta-analysis of functional neuroimaging studies of mind-wandering and related spontaneous thought processes | 2015 | Meta-analysis | |
| Investigating the Functional Heterogeneity of the Default Mode Network Using Coordinate-Based Meta-Analytic Modeling | 2009 | Meta-analysis | |
| The Default Mode Network in Healthy Individuals: A Systematic Review and Meta-Analysis Healthy individuals | 2016 | Systematic review and meta-analysis | |
| Dreaming as mind wandering: evidence from functional neuroimaging and first-person content reports. | 2013 | Systematic review with meta-analytic comparison | |
| Default Mode Network Modulation by Psychedelics: A Systematic Review Participants from included studies | 2022 | Systematic review |
Citations in the library
Cites 49
- The Brain's Default Mode Network Annual Review of Neuroscience May 4, 2015
- Default Mode Network Activity and Connectivity in Psychopathology Annual Review of Clinical Psychology March 29, 2012
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences April 11, 2016
and 44 more in the library