LSD Relaxes Structural Constraints on Brain Dynamics and Default Mode Decoupling Tracks Ego Dissolution

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.