N,N-dimethyltryptamine effects on connectome harmonics, subjective experience and comparative psychedelic experiences

Introduction

Understanding how subjective experience emerges from the interplay between brain structure and function is a central aim of contemporary neuroscience. Psychedelic compounds provide a tractable means to probe this relationship because their action on neurotransmitter systems produces widespread changes in brain activity that propagate across the structural connectome, the brain's network of white-matter pathways. The authors adopt connectome harmonic decomposition (CHD), a mathematical framework that represents cortical activity as contributions from intrinsic spatial modes of the structural connectome (connectome harmonics), analogous to how the Fourier transform decomposes signals into temporal frequencies. Low-frequency connectome harmonics capture coarse-grained, global patterns of activity tied closely to large-scale structural topology, whereas high-frequency harmonics index finer-grained, more localised deviations from that topology. Vohryzek and colleagues set out to characterise how intravenous N,N-dimethyltryptamine (DMT), a potent serotonergic psychedelic with a rapid onset and short duration, alters the brain's connectome harmonic landscape. Based on prior CHD studies of LSD, psilocybin and ketamine, they hypothesised that DMT would reduce the contribution of low-frequency harmonics and increase high-frequency contributions, and that it would broaden the repertoire of harmonics (increase repertoire entropy). The brief and predictable time-course of intravenous DMT also enabled the investigators to test whether CHD-derived measures (energy spectrum difference and repertoire entropy) track subjective intensity ratings in a time-resolved, within-session manner, rather than only in time-averaged recordings.