Serotonin 2A receptor signaling underlies LSD-induced alteration of the neural response to dynamic changes in music
Using BOLD fMRI tonality‑tracking in 25 healthy adults given placebo, LSD and LSD pretreated with the 5‑HT2A antagonist ketanserin, the study shows that 5‑HT2A receptor signalling mediates LSD‑induced alterations in neural tracking of dynamic tonal structure in music. These changes occur across auditory, musical, memory, emotion and self‑referential brain regions and likely underlie the increased emotionality, connectedness and perceived meaningfulness of music during psychedelic states.
Authors
- Franz Vollenweider
- Katrin Preller
- Frederick Barrett
Published
Abstract
Classic psychedelic drugs (serotonin 2A, or 5HT2A, receptor agonists) have notable effects on music listening. In the current report, blood oxygen level-dependent (BOLD) signal was collected during music listening in 25 healthy adults after administration of placebo, lysergic acid diethylamide (LSD), and LSD pretreated with the 5HT2A antagonist ketanserin, to investigate the role of 5HT2A receptor signaling in the neural response to the time-varying tonal structure of music. Tonality-tracking analysis of BOLD data revealed that 5HT2A receptor signaling alters the neural response to music in brain regions supporting basic and higher-level musical and auditory processing, and areas involved in memory, emotion, and self-referential processing. This suggests a critical role of 5HT2A receptor signaling in supporting the neural tracking of dynamic tonal structure in music, as well as in supporting the associated increases in emotionality, connectedness, and meaningfulness in response to music that are commonly observed after the administration of LSD and other psychedelics. Together, these findings inform the neuropsychopharmacology of music perception and cognition, meaningful music listening experiences, and altered perception of music during psychedelic experiences.
Research Summary of 'Serotonin 2A receptor signaling underlies LSD-induced alteration of the neural response to dynamic changes in music'
Introduction
Barrett and colleagues situate the study in the context that classic psychedelics (psilocybin, LSD, DMT) act primarily at serotonin 2A (5HT2A) receptors and profoundly alter perception, cognition and emotion. Prior work shows both that 5HT2A signalling can change neuronal responses along the auditory pathway and that psychedelics alter subjective responses to music, increasing emotionality, imagery and personal relevance. The authors note that music engages both primary auditory processing and a wide set of domain-general networks involved in memory, emotion and self-referential processing, many of which densely express 5HT2A receptors, suggesting a neurobiological overlap that could explain altered music experience during psychedelic states. This study therefore set out to test whether 5HT2A receptor signalling underlies LSD-induced changes in the neural response to the time-varying tonal structure of music. Using a computational model of tonal centre dynamics mapped onto a toroidal representation (toroidal/toroidal surface basis functions decomposed via spherical harmonics), the investigators applied a ‘‘tonality-tracking’’ (TT) analysis to fMRI BOLD data acquired while participants listened to personally meaningful, neutral and meaningless music under placebo, LSD and LSD after pretreatment with the 5HT2A antagonist ketanserin. The goal was to identify brain regions in which neural tracking of dynamic tonal structure was modulated by LSD and by blockade of 5HT2A signalling.
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Study Details
- Study Typeindividual
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- APA Citation
Barrett, F. S., Preller, K. H., Herdener, M., Janata, P., & Vollenweider, F. X. (2018). Serotonin 2A receptor signaling underlies LSD-induced alteration of the neural response to dynamic changes in music. Cerebral Cortex, 28(11), 3939-3950. https://doi.org/10.1093/cercor/bhx257
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Aharon-Almagor, A., Barrett, F. S. · Research Square (2022)
Vollenweider, F. X., Smallridge, J. W. · Pharmacopsychiatry (2022)
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Pallavicini, C., Vilas, M. G., Villarreal, M. et al. · NeuroImage (2019)
Barrett, F. S., Preller, K. H., Kaelen, M. · International Review of Psychiatry (2018)
Carhart-Harris, R. L. · Neuropharmacology (2018)
Swanson, L. R. · Frontiers in Pharmacology (2018)
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