Within the field of cognitive neuroscience, the study of music has provided valuable insights into the functional organization of the human brain due to music’s recruitment of large-scale brain networks involved in attention ( Janata, 2005), working memory ( Kumar et al., 2016 Zatorre et al., 1994), episodic memory ( Janata, 2009 Watanabe et al., 2008), motor function ( Zatorre et al., 2007) and emotion ( Koelsch, 2014 Trost et al., 2012). Music is a highly dynamic and multi-dimensional stimulus, consisting of distinct acoustic features, such as pitch, loudness, tempo, rhythm and timbre. The capacity of music to elicit emotions has been utilised by humans across cultures for millennia ( Morley, 2013 Nettl, Bruno, 1956). The findings shed light on how the brain processes music under LSD, and provide a neurobiological basis for the usefulness of music in psychedelic therapy. Most notable changes in brain activity and connectivity were associated with the component timbral complexity, representing the complexity of the music’s spectral distribution, and these occurred in brain networks previously identified for music-perception and music-evoked emotion, and showed an association with enhanced music-evoked feelings of wonder under LSD. Results showed pronounced cortical and subcortical changes in music-evoked brain activity under LSD. Psycho-physiological interactions (PPIs) were carried out to further interrogate underlying music-specific changes in functional connectivity under LSD. Differences between conditions were assessed at group level subsequently, and were related to changes in music-evoked emotions via correlation analyses. Dynamic time courses for acoustic features were extracted from the music excerpts, and were entered into subject-level fMRI analyses as regressors of interest. 16 healthy participants were enrolled in magnetic resonance imaging (fMRI) while listening to a 7-minute music piece under eyes-closed conditions on two separate visits (LSD (75 mcg) and placebo). The primary objective of this study was to investigate the acute effects of LSD on music-evoked brain-activity under naturalistic music listening conditions. Psychedelic drugs such as lysergic acid diethylamide (LSD) temporary disintegrate the normal hierarchy of brain functioning, and produce profound subjective effects, including enhanced music-evoked emotion. Neuroimaging studies highlight a hierarchy of brain networks involved in music perception. Music is a highly dynamic stimulus, and consists of distinct acoustic features, such as pitch, rhythm and timbre.
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