PMID- 35500840 OWN - NLM STAT- MEDLINE DCOM- 20220913 LR - 20220919 IS - 2451-9030 (Electronic) IS - 2451-9022 (Linking) VI - 7 IP - 9 DP - 2022 Sep TI - Characterizing Thalamocortical (Dys)connectivity Following D-Amphetamine, LSD, and MDMA Administration. PG - 885-894 LID - S2451-9022(22)00096-9 [pii] LID - 10.1016/j.bpsc.2022.04.003 [doi] AB - BACKGROUND: Patients with psychotic disorders present alterations in thalamocortical intrinsic functional connectivity as measured by resting-state functional magnetic resonance imaging. Specifically, thalamic intrinsic functional connectivity is increased with sensorimotor cortices (hyperconnectivity) and decreased with prefrontal limbic cortices (hypoconnectivity). Psychedelics such as lysergic acid diethlyamide (LSD) elicit similar thalamocortical hyperconnectivity with sensorimotor areas in healthy volunteers. It is unclear whether LSD also induces thalamocortical hypoconnectivity with prefrontal limbic cortices, because current findings are equivocal. Thalamocortical hyperconnectivity was associated with psychotic symptoms in patients and substance-induced altered states of consciousness in healthy volunteers. Thalamocortical dysconnectivity is likely evoked by altered neurotransmission, e.g., via dopaminergic excess in psychotic disorders and serotonergic agonism in psychedelic-induced states. It is unclear whether thalamocortical dysconnectivity is also elicited by amphetamine-type substances, broadly releasing monoamines (i.e., dopamine, norepinephrine) but producing fewer perceptual effects than psychedelics. METHODS: We administrated LSD, d-amphetamine, and 3,4-methylenedioxymethamphetamine (MDMA) in 28 healthy volunteers and investigated their effects on thalamic intrinsic functional connectivity with 2 brain networks (auditory-sensorimotor and salience networks, corresponding to sensorimotor and prefrontal limbic cortices, respectively), using a double-blind, placebo-controlled, crossover design. RESULTS: All active substances elicited auditory-sensorimotor-thalamic hyperconnectivity compared with placebo, despite predominantly distinct pharmacological actions and subjective effects. LSD-induced effects correlated with subjective changes in perception, indicating a link between hyperconnectivity and psychedelic-type perceptual alterations. Unlike d-amphetamine and MDMA, which induced hypoconnectivity with the salience network, LSD elicited hyperconnectivity. D-amphetamine and MDMA evoked similar thalamocortical dysconnectivity patterns. CONCLUSIONS: Psychedelics, empathogens, and psychostimulants evoke thalamocortical hyperconnectivity with sensorimotor areas, akin to findings in patients with psychotic disorders. CI - Copyright (c) 2022 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. Electronic address: mihai.avram@uksh.de. FAU - Muller, Felix AU - Muller F AD - Department of Psychiatry, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland. 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. FAU - Andreou, Christina AU - Andreou C AD - Translational Psychiatry, Department of Psychiatry and Psychotherapy, 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220429 PL - United States TA - Biol Psychiatry Cogn Neurosci Neuroimaging JT - Biological psychiatry. Cognitive neuroscience and neuroimaging JID - 101671285 RN - 0 (Hallucinogens) RN - 8NA5SWF92O (Lysergic Acid Diethylamide) RN - ITO20DAO7J (Lysergic Acid) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) RN - TZ47U051FI (Dextroamphetamine) SB - IM CIN - Biol Psychiatry Cogn Neurosci Neuroimaging. 2022 Sep;7(9):849-851. PMID: 36084963 MH - Cross-Over Studies MH - Dextroamphetamine MH - Double-Blind Method MH - *Hallucinogens/pharmacology MH - Humans MH - *Lysergic Acid MH - Lysergic Acid Diethylamide/pharmacology MH - *N-Methyl-3,4-methylenedioxyamphetamine/pharmacology OTO - NOTNLM OT - LSD OT - MDMA OT - Psychedelics OT - Psychotic disorders OT - Resting-state fMRI OT - Thalamocortical dysconnectivity OT - d-Amphetamine EDAT- 2022/05/03 06:00 MHDA- 2022/09/14 06:00 CRDT- 2022/05/02 19:27 PHST- 2022/01/21 00:00 [received] PHST- 2022/03/28 00:00 [revised] PHST- 2022/04/13 00:00 [accepted] PHST- 2022/05/03 06:00 [pubmed] PHST- 2022/09/14 06:00 [medline] PHST- 2022/05/02 19:27 [entrez] AID - S2451-9022(22)00096-9 [pii] AID - 10.1016/j.bpsc.2022.04.003 [doi] PST - ppublish SO - Biol Psychiatry Cogn Neurosci Neuroimaging. 2022 Sep;7(9):885-894. doi: 10.1016/j.bpsc.2022.04.003. Epub 2022 Apr 29.