Effective Connectivity of Thalamocortical Interactions Following d-Amphetamine, LSD, and MDMA Administration

• DOI: 10.1016/j.bpsc.2023.07.010
• Publication Date: 2023-07-31T16:13:42Z
• Authors: Mihai Avram; Felix Müller; Katrin H. Preller; Adeel Razi; Helena Rogg; Alexandra Korda; Friederike Holze; Patrick Vizeli; Laura Ley; Matthias E. Liechti; Stefan Borgwardt
• Keywords: Lysergic acid diethylamide; MDMA; Psychotomimetic

While the exploration of serotonergic psychedelics as psychiatric medicines deepens, so does pressure to better understand how these compounds act on brain. We used a double-blind, placebo-controlled, crossover design and administered lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), d-amphetamine in 25 healthy participants. By employing spectral dynamic causal modeling, we mapped substance-induced changes effective-connectivity between thalamus different cortex types (unimodal vs. transmodal) derived from previous study resting-state functional magnetic resonance imaging (fMRI) data. Due distinct pharmacological modes action three substances, were able investigate specific effects mainly driven by neurotransmitter systems thalamocortical corticothalamic interactions. Compared placebo, all substances increased unimodal cortices, whereas influence cortices was reduced. These results indicate bottom-up decreased top-down information flow some cortices. However, for amphetamines, found opposite when examining with transmodal covering parts salience network. Intriguingly, LSD both indicating breach hierarchical organization ongoing brain activity. Results advance our knowledge concerning refine current models aiming explain underlying neurobiological processes.