Brunel, J. | Search bioRxiv

bioRxiv2026

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 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.

neuroscience↗

bioRxiv2026

LSD Reconfigures Cortical Dynamics Through Faster Brain Rhythms and Increased Fractal Dimension

Lysergic acid diethylamide (LSD) profoundly alters conscious experience, yet the electrophysiological mechanisms by which it reshapes neural dynamics remain incompletely understood. A hallmark of psychedelic states is widespread cortical desynchronization, typically inferred from reductions in spectral power, but whether such effects reflect genuine weakening of neural oscillations or are confounded by shifts in oscillatory peak frequencies remains unresolved. Here, we address this gap by combining source-resolved magnetoencephalography (MEG), spectral parameterization, temporal complexity metrics, and interpretable machine learning in an LSD versus placebo design, with and without music. We show that LSD induces robust, spatially structured increases in alpha and beta peak frequencies alongside genuine attenuation of oscillatory power, with these effects displaying partly dissociable cortical patterns. Beyond rhythmic activity, LSD is associated with flattening of the aperiodic 1/f spectral slope and increased neural signal fractality and complexity, preferentially affecting sensory, language, emotion, and imagery-related networks while sparing motor cortex. Machine-learning analyses further identify peak-frequency shifts, aperiodic parameters, and complexity measures as key discriminators of the psychedelic state. Music does not robustly amplify these neural signatures and instead shows a trend toward attenuation. Together, these findings provide a comprehensive electrophysiological account of how LSD reorganizes large-scale human brain dynamics and highlight features that may differentiate its neural signature from that of other psychedelics.

neuroscience↗