PMID- 37532129 OWN - NLM STAT- MEDLINE DCOM- 20240508 LR - 20240508 IS - 2451-9030 (Electronic) IS - 2451-9022 (Linking) VI - 9 IP - 5 DP - 2024 May TI - Effective Connectivity of Thalamocortical Interactions Following d-Amphetamine, LSD, and MDMA Administration. PG - 522-532 LID - S2451-9022(23)00191-X [pii] LID - 10.1016/j.bpsc.2023.07.010 [doi] AB - BACKGROUND: While the exploration of serotonergic psychedelics as psychiatric medicines deepens, so does the pressure to better understand how these compounds act on the brain. METHODS: We used a double-blind, placebo-controlled, crossover design and administered lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), and d-amphetamine in 25 healthy participants. By using spectral dynamic causal modeling, we mapped substance-induced changes in effective connectivity between the thalamus and different cortex types (unimodal vs. transmodal) derived from a previous study with resting-state functional magnetic resonance imaging data. Due to the distinct pharmacological modes of action of the 3 substances, we were able to investigate specific effects mainly driven by different neurotransmitter systems on thalamocortical and corticothalamic interactions. RESULTS: Compared with placebo, all 3 substances increased the effective connectivity from the thalamus to specific unimodal cortices, whereas the influence of these cortices on the thalamus was reduced. These results indicate increased bottom-up and decreased top-down information flow between the thalamus and some unimodal cortices. However, for the amphetamines, we found the opposite effects when examining the effective connectivity with transmodal cortices, including parts of the salience network. Intriguingly, LSD increased the effective connectivity from the thalamus to both unimodal and transmodal cortices, indicating a breach in the hierarchical organization of ongoing brain activity. CONCLUSIONS: The results advance our knowledge about the action of psychedelics on the brain and refine current models aiming to explain the underlying neurobiological processes. CI - Copyright (c) 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved. FAU - Avram, Mihai AU - Avram M AD - Translational Psychiatry, Department of Psychiatry and Psychotherapy, University of Lubeck, Lubeck, Germany; Center of Brain, Behavior, and Metabolism, University of Lubeck, Lubeck, Germany. Electronic address: mihai.avram@uksh.de. FAU - Muller, Felix AU - Muller F AD - Department of Psychiatry, University of Basel, Basel, Switzerland. FAU - Preller, Katrin H AU - Preller KH AD - Pharmaco-Neuroimaging and Cognitive-Emotional Processing, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland. FAU - Razi, Adeel AU - Razi A AD - Turner Institute for Brain and Mental Health, Monash University, Clayton, Victoria, Australia. FAU - Rogg, Helena AU - Rogg H AD - Translational Psychiatry, Department of Psychiatry and Psychotherapy, University of Lubeck, Lubeck, Germany. FAU - Korda, Alexandra AU - Korda A AD - Translational Psychiatry, Department of Psychiatry and Psychotherapy, University of Lubeck, Lubeck, Germany; Center of Brain, Behavior, and Metabolism, University of Lubeck, Lubeck, Germany. FAU - Holze, Friederike AU - Holze F AD - Division of Clinical Pharmacology and Toxicology, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland. FAU - Vizeli, Patrick AU - Vizeli P AD - Division of Clinical Pharmacology and Toxicology, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland. FAU - Ley, Laura AU - Ley L AD - Division of Clinical Pharmacology and Toxicology, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland. FAU - Liechti, Matthias E AU - Liechti ME AD - Division of Clinical Pharmacology and Toxicology, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland. FAU - Borgwardt, Stefan AU - Borgwardt S AD - Translational Psychiatry, Department of Psychiatry and Psychotherapy, University of Lubeck, Lubeck, Germany; Center of Brain, Behavior, and Metabolism, University of Lubeck, Lubeck, Germany. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20230731 PL - United States TA - Biol Psychiatry Cogn Neurosci Neuroimaging JT - Biological psychiatry. Cognitive neuroscience and neuroimaging JID - 101671285 RN - 8NA5SWF92O (Lysergic Acid Diethylamide) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) RN - 0 (Hallucinogens) RN - TZ47U051FI (Dextroamphetamine) SB - IM MH - Humans MH - *Lysergic Acid Diethylamide/pharmacology/administration & dosage MH - *N-Methyl-3,4-methylenedioxyamphetamine/pharmacology/administration & dosage MH - *Thalamus/drug effects/diagnostic imaging/physiology MH - Male MH - Double-Blind Method MH - Adult MH - *Magnetic Resonance Imaging MH - *Hallucinogens/pharmacology/administration & dosage MH - *Dextroamphetamine/pharmacology/administration & dosage MH - *Cross-Over Studies MH - Female MH - *Cerebral Cortex/drug effects/diagnostic imaging/physiology MH - Young Adult MH - Neural Pathways/drug effects MH - Connectome OTO - NOTNLM OT - Dynamic causal modeling OT - Effective connectivity OT - LSD OT - MDMA OT - Psychedelics OT - Transmodal cortex OT - Unimodal cortex OT - d-Amphetamine EDAT- 2023/08/03 01:06 MHDA- 2024/05/09 00:47 CRDT- 2023/08/02 19:15 PHST- 2023/04/03 00:00 [received] PHST- 2023/07/17 00:00 [revised] PHST- 2023/07/18 00:00 [accepted] PHST- 2024/05/09 00:47 [medline] PHST- 2023/08/03 01:06 [pubmed] PHST- 2023/08/02 19:15 [entrez] AID - S2451-9022(23)00191-X [pii] AID - 10.1016/j.bpsc.2023.07.010 [doi] PST - ppublish SO - Biol Psychiatry Cogn Neurosci Neuroimaging. 2024 May;9(5):522-532. doi: 10.1016/j.bpsc.2023.07.010. Epub 2023 Jul 31.