Mapping Pharmacologically-induced Functional Reorganisation onto the Brain’s Neurotransmitter Landscape
Adapa, R., Araújo, D. B., Carhart-Harris, R. L., Golkowski, D., Hansen, J. Y., Ilg, R., Jordan, D., Luppi, A. I., Manktelow, A. E., Menon, D. K., Misic, B., Naci, L., Owen, A. M., Peattie, A. R. D., Ranft, A., Roseman, L., Sensi, S. L., Stamatakis, E. A.
This theory-building preprint (2022) uses data from fMRI and PET scans (of the brain) to show how different pharmacological interventions (including psychedelics) interact with neurotransmitters. The results show opposite routes, but similar mechanisms, as to how psychedelics and anaesthetics (e.g. ketamine) interact with the brain (molecular chemoarchitecture).
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 18 neurotransmitter receptors and transporters obtained from Positron Emission Tomography, and the regional changes in functional MRI connectivity induced by 7 different mind-altering drugs including anaesthetics, psychedelics, and cognitive enhancers. Our results reveal that psychoactive drugs exert their effects on brain function by engaging multiple neurotransmitter systems. Intriguingly, the effects of both anaesthetics and psychedelics on brain function, though opposite, 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.