LSD Relaxes Structural Constraints on Brain Dynamics and Default Mode Decoupling Tracks Ego Dissolution
OpenAlex – March 05, 2026
Source: OpenAlex
Summary
Psychedelics like LSD significantly alter brain function, revealing a remarkable decoupling of low-frequency brain activity from structural constraints. In a study involving 30 participants, LSD led to a 40% increase in flexibility within the default mode network, which is associated with ego dissolution. While low-frequency activity showed widespread reorganization, high-frequency gamma activity underwent selective adjustments. This suggests that psychedelics promote a unique rebalancing of neural dynamics, potentially enhancing therapeutic effects by loosening rigid structural limitations and improving communication among brain networks involved in self-awareness and perception.
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.