PMID- 37315149 OWN - NLM STAT- MEDLINE DCOM- 20230616 LR - 20240214 IS - 2375-2548 (Electronic) IS - 2375-2548 (Linking) VI - 9 IP - 24 DP - 2023 Jun 16 TI - In vivo mapping of pharmacologically induced functional reorganization onto the human brain's neurotransmitter landscape. PG - eadf8332 LID - 10.1126/sciadv.adf8332 [doi] LID - eadf8332 AB - To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brain's rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically induced macroscale functional reorganization, by relating the regional distribution of 19 neurotransmitter receptors and transporters obtained from positron emission tomography, and the regional changes in functional magnetic resonance imaging connectivity induced by 10 different mind-altering drugs: propofol, sevoflurane, ketamine, lysergic acid diethylamide (LSD), psilocybin, N,N-Dimethyltryptamine (DMT), ayahuasca, 3,4-methylenedioxymethamphetamine (MDMA), modafinil, and methylphenidate. Our results reveal a many-to-many mapping between psychoactive drugs' effects on brain function and multiple neurotransmitter systems. The effects of both anesthetics and psychedelics on brain function are organized along hierarchical gradients of brain structure and function. Last, we show that regional co-susceptibility to pharmacological interventions recapitulates co-susceptibility to disorder-induced structural alterations. Collectively, these results highlight rich statistical patterns relating molecular chemoarchitecture and drug-induced reorganization of the brain's functional architecture. FAU - Luppi, Andrea I AU - Luppi AI AUID- ORCID: 0000-0002-3461-6431 AD - Division of Anaesthesia, University of Cambridge, Cambridge, UK. AD - Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK. AD - Leverhulme Centre for the Future of Intelligence, University of Cambridge, Cambridge, UK. AD - The Alan Turing Institute, London, UK. AD - McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Montreal, QC, Canada. FAU - Hansen, Justine Y AU - Hansen JY AUID- ORCID: 0000-0003-3142-7480 AD - McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Montreal, QC, Canada. FAU - Adapa, Ram AU - Adapa R AUID- ORCID: 0000-0002-9845-8532 AD - Division of Anaesthesia, University of Cambridge, Cambridge, UK. FAU - Carhart-Harris, Robin L AU - Carhart-Harris RL AD - Psychedelics Division - Neuroscape, Department of Neurology, University of California San Francisco, San Francisco, CA, USA. FAU - Roseman, Leor AU - Roseman L AUID- ORCID: 0000-0001-9990-6029 AD - Center for Psychedelic Research, Department of Brain Sciences, Imperial College London, London, UK. FAU - Timmermann, Christopher AU - Timmermann C AUID- ORCID: 0000-0002-2281-377X AD - Center for Psychedelic Research, Department of Brain Sciences, Imperial College London, London, UK. FAU - Golkowski, Daniel AU - Golkowski D AD - Department of Neurology, Klinikum rechts der Isar, Technical University Munich, Munchen, Germany. FAU - Ranft, Andreas AU - Ranft A AUID- ORCID: 0000-0002-0530-0796 AD - School of Medicine, Department of Anesthesiology and Intensive Care, Technical University of Munich, Munich, Germany. FAU - Ilg, Rudiger AU - Ilg R AD - Department of Neurology, Klinikum rechts der Isar, Technical University Munich, Munchen, Germany. AD - Department of Neurology, Asklepios Clinic, Bad Tolz, Germany. FAU - Jordan, Denis AU - Jordan D AD - Department of Anaesthesiology and Intensive Care Medicine, Klinikum rechts der Isar, Technical University Munich, Munchen, Germany. AD - University of Applied Sciences and Arts Northwestern Switzerland, Muttenz, Switzerland. FAU - Bonhomme, Vincent AU - Bonhomme V AUID- ORCID: 0000-0001-6356-547X AD - Department of Anesthesia and Intensive Care Medicine, Liege University Hospital, Liege, Belgium. AD - Anesthesia and Perioperative Neuroscience Laboratory, GIGA-Consciousness Thematic Unit, GIGA-Research, Liege University, Liege, Belgium. FAU - Vanhaudenhuyse, Audrey AU - Vanhaudenhuyse A AUID- ORCID: 0000-0002-4288-9237 AD - Department of Anesthesia and Intensive Care Medicine, Liege University Hospital, Liege, Belgium. FAU - Demertzi, Athena AU - Demertzi A AUID- ORCID: 0000-0001-8021-3759 AD - GIGA-Cyclotron Research Centre-In Vivo Imaging, University of Liege, Liege, Belgium. FAU - Jaquet, Oceane AU - Jaquet O AUID- ORCID: 0000-0002-6460-7982 AD - Department of Anesthesia and Intensive Care Medicine, Liege University Hospital, Liege, Belgium. FAU - Bahri, Mohamed Ali AU - Bahri MA AUID- ORCID: 0000-0002-6919-3360 AD - GIGA-Cyclotron Research Centre-In Vivo Imaging, University of Liege, Liege, Belgium. FAU - Alnagger, Naji L N AU - Alnagger NLN AUID- ORCID: 0000-0002-7880-6237 AD - Department of Anesthesia and Intensive Care Medicine, Liege University Hospital, Liege, Belgium. FAU - Cardone, Paolo AU - Cardone P AUID- ORCID: 0000-0002-8537-2123 AD - Department of Anesthesia and Intensive Care Medicine, Liege University Hospital, Liege, Belgium. FAU - Peattie, Alexander R D AU - Peattie ARD AUID- ORCID: 0000-0003-2115-7640 AD - Division of Anaesthesia, University of Cambridge, Cambridge, UK. AD - Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK. FAU - Manktelow, Anne E AU - Manktelow AE AUID- ORCID: 0000-0002-2319-1669 AD - Division of Anaesthesia, University of Cambridge, Cambridge, UK. FAU - de Araujo, Draulio B AU - de Araujo DB AUID- ORCID: 0000-0002-6934-2485 AD - Brain Institute, Federal University of Rio Grande do Norte, Natal, RN, Brazil. FAU - Sensi, Stefano L AU - Sensi SL AUID- ORCID: 0000-0002-0710-2574 AD - Department of Neuroscience and Imaging and Clinical Science, Center for Advanced Studies and Technology, Institute for Advanced Biomedical Technologies, University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy. AD - Institute for Memory Impairments and Neurological Disorders, University of California-Irvine, Irvine, CA, USA. FAU - Owen, Adrian M AU - Owen AM AUID- ORCID: 0000-0002-5738-3765 AD - Department of Psychology and Department of Physiology and Pharmacology, Western Institute for Neuroscience (WIN), Western University, London, ON, Canada. FAU - Naci, Lorina AU - Naci L AUID- ORCID: 0000-0001-9630-3978 AD - Trinity College Institute of Neuroscience, School of Psychology, Trinity College Dublin, Dublin, Ireland. FAU - Menon, David K AU - Menon DK AUID- ORCID: 0000-0002-3228-9692 AD - Division of Anaesthesia, University of Cambridge, Cambridge, UK. AD - Wolfon Brain Imaging Centre, University of Cambridge, Cambridge, UK. FAU - Misic, Bratislav AU - Misic B AUID- ORCID: 0000-0003-0307-2862 AD - McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Montreal, QC, Canada. FAU - Stamatakis, Emmanuel A AU - Stamatakis EA AUID- ORCID: 0000-0001-6955-9601 AD - Division of Anaesthesia, University of Cambridge, Cambridge, UK. AD - Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK. LA - eng GR - MR/M009041/1/MRC_/Medical Research Council/United Kingdom PT - Journal Article DEP - 20230614 PL - United States TA - Sci Adv JT - Science advances JID - 101653440 RN - 690G0D6V8H (Ketamine) RN - 0 (Membrane Transport Proteins) RN - 207ZZ9QZ49 (Methylphenidate) RN - R3UK8X3U3D (Modafinil) SB - IM MH - Humans MH - Brain MH - *Ketamine MH - Membrane Transport Proteins MH - *Methylphenidate MH - Modafinil PMC - PMC10266734 EDAT- 2023/06/14 19:10 MHDA- 2023/06/16 06:42 PMCR- 2023/06/14 CRDT- 2023/06/14 14:03 PHST- 2023/06/16 06:42 [medline] PHST- 2023/06/14 19:10 [pubmed] PHST- 2023/06/14 14:03 [entrez] PHST- 2023/06/14 00:00 [pmc-release] AID - adf8332 [pii] AID - 10.1126/sciadv.adf8332 [doi] PST - ppublish SO - Sci Adv. 2023 Jun 16;9(24):eadf8332. doi: 10.1126/sciadv.adf8332. Epub 2023 Jun 14.