Study: Transcriptomics-informed modeling of pharmacological neuroimaging effects of LSD

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

SPECIES:
Human

DESCRIPTION:
This BALSA study contains all sources of data needed to reproduce the main findings reported in our paper, as well as all brain maps illustrated in the main and supplementary figures. An open-source Python-based implementation of our transcriptomics-informed biophysical model can be downloaded from https://github.com/murraylab/braintrips.

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. Previously, using pharmacological neuroimaging we found that neural and experiential effects of lysergic acid diethylamide (LSD) are attributable to agonism of the serotonin-2A receptor. Here, we integrate brain-wide transcriptomics with biophysically-based large-scale circuit modeling to simulate acute neuromodulatory effects of LSD on human cortical large-scale spatiotemporal dynamics. Our model captures the inter-areal topography of LSD-induced changes in cortical BOLD functional connectivity. These findings suggest serotonin-2A-mediated modulation of pyramidal-neuronal gain is a circuit mechanism through which LSD alters cortical functional topography. Individual-subject model fitting captures patterns of individual neural differences in pharmacological response related to altered states of consciousness. This work establishes a framework for linking molecular-level manipulations to systems-level functional alterations, with implications for precision medicine.

PUBLICATION:
eLife - DOI: 10.1101/2021.01.31.429016

AUTHORS:

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

INSTITUTIONS:
  • Yale University
  • University Hospital for Psychiatry Zurich