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. We combine 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 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 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. These findings provide an electrophysiological account of how LSD reorganizes large-scale human brain dynamics and highlight features that may differentiate its neural signature from other psychedelics. Psychedelics are potent psychoactive compounds that elicit profound alterations in conscious experience, spanning heightened sensory perception, vivid imagery, and distortions in the sense of self1.
Beyond their characteristic phenomenology, these compounds offer a powerful experimental lever for perturbing large-scale brain dynamics and probing the neural mechanisms by which the brain gives rise to mind2,3,4,5. Psychedelics have been used in rituals and cultural settings for thousands of years6, often alongside music7. Classic psychedelics—including psilocybin, N, N-dimethyltryptamine (DMT), and lysergic acid diethylamide (LSD)—exert their profound effects primarily through agonism at the 5-HT2A receptor.
Among these, LSD is uniquely characterized by its additional affinity for dopaminergic receptors8, its extreme potency (producing effects at remarkably low doses), and its extended receptor kinetics. Despite these well-known pharmacological properties, the precise manner in which LSD perturbs cortical dynamics—spanning oscillatory rhythms, aperiodic spectral structure, and temporal signal complexity—and how these effects are shaped by sensory stimuli, such as music, remains poorly understood. Modern neuroimaging has played a central role in uncovering how psychedelics alter large-scale brain function and core aspects of conscious experience, a process thought to support their therapeutic effect5,9,10.
These mechanisms have been investigated across different modalities, including positron emission tomography (PET)11, functional MRI (fMRI)12, electroencaphelography (EEG)13, and magnetoencephalography (MEG)14. fMRI has been especially influential in understanding the psychedelic state (e.g., ref. 15). However, the fMRI signal reflects neural activity only indirectly via blood oxygenation, and psychedelics strongly modulate neurovascular processes16. As a result, psychedelic-induced BOLD changes may partly reflect disruption in neurovascular coupling rather than neural dynamics per se16.
Extract — continue reading at the source.
