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Mapping Pharmacologically-induced Functional Reorganisation onto the Brain's Neurotransmitter Landscape

Luppi, A. I.; Hansen, J. Y.; Adapa, R.; Carhart-Harris, R. L.; Roseman, L.; Golkowski, D.; Ranft, A.; Ilg, R.; Jordan, D.; Peattie, A. R. D.; Manktelow, A. E.; de Araujo, D. B.; Sensi, S. L.; Owen, A. M.; Naci, L.; Menon, D. K.; Misic, B.; Stamatakis, E. A.

2022-07-13 neuroscience
10.1101/2022.07.12.499688 bioRxiv
Show abstract

To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brains 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 brains functional architecture.

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