LSD Relaxes Structural Constraints on Brain Dynamics and Default Mode Decoupling Tracks Ego Dissolution
Venkatesh Subramani, Annalisa Pascarella, Jérémy Brunel, Yann Harel, Suresh Muthukumaraswamy, Robin Carhart-Harris, Karim Jerbi, Giulia Lioi, Nicolas Farrugia
bioRxiv (Cold Spring Harbor Laboratory) March 5, 2026 preprint DOI: 10.64898/2026.03.02.709138 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study |
|---|---|
| Population | Humans under lysergic acid diethylamide (LSD) and placebo |
| Intervention | Lysergic acid diethylamide (LSD) |
| Topics | Default mode network Ego dissolution LSD |
| Keywords | Decoupling probability Magnetoencephalography Dynamical decoupling Coupling piping Flexibility engineering Electrophysiology Electroencephalography Biological system Connectome Stimulus psychology Brain function Communication Control reconfiguration |
| Key findings | LSD induces a global decoupling of low-frequency brain activity from anatomical constraints and frequency-selective reorganization of gamma-band activity within the default-mode network, which predicts ego dissolution intensity. |
Abstract
Abstract Psychedelics profoundly alter conscious experience, yet how they reshape the relationship between brain anatomy and function remains unclear. In particular, it is unknown whether psychedelic states reflect a global disruption of structure–function organization or a frequency– and network-specific reconfiguration of neural dynamics relative to the structural connectome. Here we address this question using source-localized magnetoencephalography mapped onto connectome harmonics to quantify structure–function coupling in humans under lysergic acid diethylamide (LSD) and placebo. LSD induces a robust decoupling of low-frequency (theta, alpha and beta) activity from anatomical constraints, indicating a global loosening of structure-aligned large-scale dynamics. In contrast, high-frequency gamma activity shows selective reorganization rather than uniform disruption. Greater gamma-band decoupling within core default-mode network regions predicts the intensity of ego dissolution across individuals, demonstrating that while LSD broadly alters large-scale dynamics, subjective loss of self is specifically linked to frequency-selective reorganization of the default-mode network. Functional decoding reveals that LSD does not produce indiscriminate disintegration but instead drives system-specific rebalancing, with preferential decoupling of visual and attentional systems and strengthened coupling within auditory networks. Together, these findings provide electrophysiological evidence that psychedelic states emerge from a frequency-dependent relaxation of structural constraints on brain activity and identify default-mode reorganization as a neural correlate of ego dissolution. These results offer a mechanistic framework for understanding how LSD may exert therapeutic effects by transiently relaxing rigid structural constraints and enhancing dynamical flexibility within networks involved in self-related processing.