LSD Relaxes Structural Constraints on Brain Dynamics: A Connectome Harmonic MEG Study

Abstract Psychedelics profoundly alter conscious experience, yet how they reshape the relationship between brain anatomy and electrophysiological dynamics remains unclear. Here we use 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. High-frequency gamma activity shows selective reorganization rather than uniform disruption. Decoupling within core default-mode network regions predicts ego dissolution intensity across individuals, linking frequency-selective DMN reorganization to subjective loss of self. Functional decoding further reveals system-specific rebalancing: visual and attentional systems preferentially decouple while auditory networks exhibit strengthened coupling. 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.