Mapping Pharmacologically-induced Functional Reorganisation onto the Brain’s Neurotransmitter Landscape
Andrea I. Luppi, Justine Y. Hansen, Ram Adapa, Robin Carhart-Harris, Leor Roseman, Christopher Timmermann, Daniel Golkowski, Andreas Ranft, Rüdiger Ilg, Denis Jordan, Vincent Bonhomme, Audrey Vanhaudenhuyse, Athena Demertzi, Océane Jaquet, Mohamed Ali Bahri, Naji Alnagger, Paolo Cardone, 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
bioRxiv (Cold Spring Harbor Laboratory) July 13, 2022 preprint DOI: 10.1101/2022.07.12.499688 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort |
|---|---|
| Interventions | propofol sevoflurane ketamine LSD psilocybin DMT ayahuasca MDMA modafinil methylphenidate |
| Keywords | Neurotransmitter receptor Neurotransmitter systems Pharmacology |
| Citations | 5 |
| Key findings | Psychoactive drugs reorganize brain function by engaging multiple neurotransmitter systems, with effects organized along hierarchical brain gradients, and regional drug susceptibility mirrors disorder-related structural vulnerability. |
Abstract
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 reorganisation, by relating the regional distribution of 19 neurotransmitter receptors and transporters obtained from Positron Emission Tomography, and the regional changes in functional MRI connectivity induced by 10 different mind-altering drugs: propofol, sevoflurane, ketamine, LSD, psilocybin, DMT, ayahuasca, MDMA, modafinil, and methylphenidate. Our results reveal that psychoactive drugs exert their effects on brain function by engaging multiple neurotransmitter systems. The effects of both anaesthetics and psychedelics on brain function are organised along hierarchical gradients of brain structure and function. Finally, 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 reorganisation of the brain’s functional architecture.