In vivo mapping of pharmacologically induced functional reorganization onto the human brain's neurotransmitter landscape.

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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.

Humans, Brain, Ketamine, Membrane Transport Proteins, Methylphenidate, Modafinil
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American Association for the Advancement of Science (AAAS)
Wellcome Trust (083660/Z/07/Z)
Medical Research Council (MR/M009041/1)
EPSRC (EP/T022159/1)
Gates Cambridge Trust (OPP 1144) [to AIL]; Wellcome Trust Research Training Fellowship (grant no. 083660/Z/07/Z), Raymond and Beverly Sackler Studentship, and the Cambridge Commonwealth Trust [to RA]; Canadian Institute for Advanced Research (CIFAR; grant RCZB/072 RG93193) [to DKM and EAS]; Cambridge Biomedical Research Centre and NIHR Senior Investigator Awards and the British Oxygen Professorship of the Royal College of Anaesthetists [to DKM]; Stephen Erskine Fellowship at Queens’ College, Cambridge [to EAS]; Natural Sciences and Engineering Research Council of Canada (NSERC Discovery Grant RGPIN #017-04265) and Canada Research Chairs Program [to BM]; Helmholtz International BigBrain Analytics & Learning Laboratory, the Natural Sciences 1435 and Engineering Research Council of Canada, and Fonds de reserches de Québec [to JYH]; Canada Excellence Research Chairs program (215063) [to AMO]; L’Oreal-Unesco for Women in Science Excellence Research Fellowship to LN]; Imperial College President’s Scholarship [to LR]; Belgian National Funds for Scientific Research (F.R.S-FNRS) [to PC and NLNA]; GIGA-Doctoral School for Health Sciences (University of Liège) [to PC]; Human Brain Project [to NLNA]; Italian Department of Education [Fondo per gli Investimenti della Ricerca di Base (FIRB) 2003; Programmi di Ricerca di Rilevante Interesse nazionale (PRIN) 2008 [to SLS]; Alex Mosley Charitable Trust and supporters of the Centre for Psychedelic Research, Ralph Metzner Distinguished Professorship at UCSF [to RLC-H];