In vivo mapping of pharmacologically induced functional reorganization onto the human brain’s neurotransmitter landscape
Science Advances – June 14, 2023
Source: OpenAlex
Summary
The human brain's response to drugs reveals a profound link between molecular structure and behavior. Neuroscience shows diverse pharmacological agents, including 10 psychedelics and anesthetics, reorganize brain function by engaging multiple neurotransmitter systems. By mapping 19 neurotransmitter receptors and transporters, a clear influence on behavior emerged. This pharmacology insight has significant implications for Psychology and Medicine, informing drug studies and our understanding of brain disorders. Crucially, regional drug susceptibility mirrors vulnerability to structural alterations seen in conditions like those linked to Tryptophan imbalances.
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.