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

Abstract

Abstract 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.