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.
Disciplines :
Neurology Neurosciences & behavior
Author, co-author :
Luppi, Andrea I ; Division of Anaesthesia, University of Cambridge, Cambridge, UK. ; Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK. ; Leverhulme Centre for the Future of Intelligence, University of Cambridge, ; The Alan Turing Institute, London, UK. ; McConnell Brain Imaging Center, Montreal Neurological Institute, McGill
Hansen, Justine Y ; McConnell Brain Imaging Center, Montreal Neurological Institute, McGill
Adapa, Ram ; Division of Anaesthesia, University of Cambridge, Cambridge, UK.
Carhart-Harris, Robin L; Psychedelics Division - Neuroscape, Department of Neurology, University of
Roseman, Leor ; Center for Psychedelic Research, Department of Brain Sciences, Imperial College
Timmermann, Christopher ; Center for Psychedelic Research, Department of Brain Sciences, Imperial College
Golkowski, Daniel; Department of Neurology, Klinikum rechts der Isar, Technical University Munich,
Ranft, Andreas ; School of Medicine, Department of Anesthesiology and Intensive Care, Technical
Ilg, Rüdiger; Department of Neurology, Klinikum rechts der Isar, Technical University Munich, ; Department of Neurology, Asklepios Clinic, Bad Tölz, Germany.
Jordan, Denis; Department of Anaesthesiology and Intensive Care Medicine, Klinikum rechts der ; University of Applied Sciences and Arts Northwestern Switzerland, Muttenz,
Bonhomme, Vincent ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'anesthésie - réanimation ; Department of Anesthesia and Intensive Care Medicine, Liege University Hospital ; Anesthesia and Perioperative Neuroscience Laboratory, GIGA-Consciousness Thematic
Vanhaudenhuyse, Audrey ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'algologie - soins palliatifs ; Department of Anesthesia and Intensive Care Medicine, Liege University Hospital
Demertzi, Athina ; Université de Liège - ULiège > GIGA > GIGA CRC In vivo Imaging - Physiology of Cognition
Jaquet, Océane ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'anesthésie - réanimation ; Department of Anesthesia and Intensive Care Medicine, Liege University Hospital
Alnagger, Naji ; Université de Liège - ULiège > GIGA > GIGA Consciousness - Coma Science Group ; Department of Anesthesia and Intensive Care Medicine, Liege University Hospital
Cardone, Paolo ; Université de Liège - ULiège > GIGA > GIGA Consciousness - Coma Science Group ; Department of Anesthesia and Intensive Care Medicine, Liege University Hospital
Peattie, Alexander R D ; Division of Anaesthesia, University of Cambridge, Cambridge, UK. ; Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Manktelow, Anne E ; Division of Anaesthesia, University of Cambridge, Cambridge, UK.
de Araujo, Draulio B ; Brain Institute, Federal University of Rio Grande do Norte, Natal, RN, Brazil.
Sensi, Stefano L ; Department of Neuroscience and Imaging and Clinical Science, Center for Advanced ; Institute for Memory Impairments and Neurological Disorders, University of
Owen, Adrian M ; Department of Psychology and Department of Physiology and Pharmacology, Western
Naci, Lorina ; Trinity College Institute of Neuroscience, School of Psychology, Trinity College
Menon, David K ; Division of Anaesthesia, University of Cambridge, Cambridge, UK. ; Wolfon Brain Imaging Centre, University of Cambridge, Cambridge, UK.
Misic, Bratislav ; McConnell Brain Imaging Center, Montreal Neurological Institute, McGill
Stamatakis, Emmanuel A ; Division of Anaesthesia, University of Cambridge, Cambridge, UK. ; Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
