Transcriptomics-informed large-scale cortical model captures topography of pharmacological neuroimaging effects of LSD

This brain modelling study finds the topographic effects (where) LSD changes functional connectivity (FC) in the brain, via the modulation of serotonin 2A pyramidal cells.

Abstract

“Psychoactive drugs can transiently perturb brain physiology while preserving brain structure. The role of physiological state in shaping neural function can therefore be investigated through neuroimaging of pharmacologically-induced effects. This paradigm has revealed that neural and experiential effects of lysergic acid diethylamide (LSD) are attributable to its agonist activity at the serotonin-2A receptor. Here, we integrate brainwide transcriptomics with biophysically-based large-scale circuit modeling to simulate acute neuromodulatory effects of LSD on human cortical dynamics. Our model captures the topographic effects of LSD-induced changes in cortical BOLD functional connectivity. These findings suggest that serotonin-2A-mediated modulation of pyramidal cell gain is the circuit mechanism through which LSD alters cortical functional topography. Individual-subject fitting reveals that the model captures patterns of individual neural differences in drug response that predict altered states of consciousness. This work establishes a framework for linking molecular-level manipulations to salient changes in brain function, with implications for precision medicine.”

Authors: Joshua B. Burt, Katrin H. Preller, Murat Demirtas, Jie Lisa Ji, John H. Krystal, Franz X. Vollenweider, Alan Anticevic & John D. Murray