LSD reconfigures the frequency-specific network landscape of the human brain

Abstract Lysergic acid diethylamide (LSD) and other psychedelic substances profoundly alter human consciousness. While several studies have demonstrated changes in brain function and connectivity associated with psychedelics, we still have a limited understanding of how LSD reshapes brain networks operating across different frequency bands. In this study, we applied the recently developed FREQ-NESS method to MEG data from 14 healthy participants who received LSD under four conditions: eyes-closed with or without music and eyes-open with or without a video stimulus. LSD significantly restructures canonical networks in the alpha and beta bands. Relative to broadband brain activity, it enhances the prominence of high alpha (12.1, 13.3 Hz) across all experimental conditions and high beta (25.3 Hz) in three conditions. Conversely, LSD decreases the prominence of low beta (18.1, 19.3 Hz) in both Open and Closed conditions and low alpha (8.5 Hz) in the latter. In addition, LSD substantially alters the spatial distributions or topographies of the networks. Under LSD, the low alpha (8.5 Hz) network shifts anteriorly toward the motor cortex, while high alpha (12.1, 13.3 Hz) becomes more localized to the visual cortex. Low beta (18.1, 19.3 Hz) expands over the temporal and occipital cortices, whereas high beta (25.3, 26.5 Hz) topographies remain unchanged. Our findings provide critical insights into the specific frequencies and spatial networks in which LSD modulates brain connectivity, adding nuance to prevailing theories about network disintegration under psychedelics. Significance statement Psychedelic substances such as lysergic acid diethylamide (LSD) profoundly alter perception and cognition, yet their effect on brain activity across different frequency bands remains unclear. Using FREQ-NESS applied to MEG data, we show that LSD reorganizes brain networks by enhancing high-frequency alpha and beta rhythms while suppressing lower-frequency counterparts. These changes occur across various experimental conditions and shift the spatial distribution of brain activity, particularly in motor and visual regions. Our findings suggest that LSD modulates brain connectivity in a frequency- and region-specific manner, offering new insights into how psychedelics alter consciousness. This work advances our understanding of LSD’s neural effects, which may be relevant for therapeutic applications and models of brain function.