The effect of lysergic acid diethylamide (LSD) on whole-brain functional and effective connectivity
Neuropsychopharmacology – April 25, 2023
Source: OpenAlex
Summary
Lysergic acid diethylamide profoundly reconfigures brain communication, a key finding for Psychology and Psychedelics and Drug Studies. Using resting state functional magnetic resonance imaging (fMRI) in 45 participants, comparing 100 μg LSD to a Placebo, brain mapping revealed widespread stronger functional connectivity and less self-inhibition. Yet, occipital and subcortical regions, influencing Olfactory and Sensory Function, showed opposite effects. This brain activity pattern, reflecting Neurotransmitter Receptor Influence on Behavior and relevant to Brain activity and meditation, accurately predicted the drug's presence 91.11% of the time.
Abstract
Abstract Psychedelics have emerged as promising candidate treatments for various psychiatric conditions, and given their clinical potential, there is a need to identify biomarkers that underlie their effects. Here, we investigate the neural mechanisms of lysergic acid diethylamide (LSD) using regression dynamic causal modelling (rDCM), a novel technique that assesses whole-brain effective connectivity (EC) during resting-state functional magnetic resonance imaging (fMRI). We modelled data from two randomised, placebo-controlled, double-blind, cross-over trials, in which 45 participants were administered 100 μg LSD and placebo in two resting-state fMRI sessions. We compared EC against whole-brain functional connectivity (FC) using classical statistics and machine learning methods. Multivariate analyses of EC parameters revealed predominantly stronger interregional connectivity and reduced self-inhibition under LSD compared to placebo, with the notable exception of weakened interregional connectivity and increased self-inhibition in occipital brain regions as well as subcortical regions. Together, these findings suggests that LSD perturbs the Excitation/Inhibition balance of the brain. Notably, whole-brain EC did not only provide additional mechanistic insight into the effects of LSD on the Excitation/Inhibition balance of the brain, but EC also correlated with global subjective effects of LSD and discriminated experimental conditions in a machine learning-based analysis with high accuracy (91.11%), highlighting the potential of using whole-brain EC to decode or predict subjective effects of LSD in the future.