In vivo mapping of pharmacologically induced functional reorganization onto the human brain’s neurotransmitter landscape
Leor Roseman, Christopher Timmermann, Daniel Golkowski, Andreas Ranft, Rüdiger Ilg, Denis Jordan, Vincent Bonhomme, Audrey Vanhaudenhuyse, Mohamed Ali Bahri, Paolo Cardone, Andrea I. Luppi, Justine Y. Hansen, Ram Adapa, Robin Carhart-Harris, Athena Demertzi, Océane Jaquet, Naji Alnagger, Alexander R. D. Peattie, Anne E. Manktelow, Dráulio Barros de Araújo, Stefano L. Sensi, Adrian M. Owen, Lorina Naci, David K. Menon, Bratislav Mišić, Emmanuel A. Stamatakis
Science Advances June 14, 2023 DOI: 10.1126/sciadv.adf8332 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study linking PET and fMRI data Peer reviewed |
|---|---|
| Population | Human brain (regional PET and fMRI data from prior studies) |
| Interventions | propofol sevoflurane ketamine lysergic acid diethylamide (LSD) psilocybin N N-Dimethyltryptamine (DMT) ayahuasca 3 4-methylenedioxymethamphetamine (MDMA) modafinil methylphenidate |
| Keywords | Pharmacology Neurotransmitter receptor Human brain |
| Citations | 65 |
| Key findings | A many-to-many mapping exists between psychoactive drugs' effects on brain function and multiple neurotransmitter systems, with drug-induced changes aligning with hierarchical brain gradients and disorder-related structural vulnerability. |
Abstract
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.