The effect of lysergic acid diethylamide (LSD) on whole-brain functional and effective connectivity
Bedford, P., Borgwardt, S., Diaconescu, A. O., Hauke, D. J., Holze, F., Ley, L., Liechti, M. E., Müller, F., Nagy-Huber, M., Roth, V., Vizeli, P., Wang, Z.
This brain modelling study used data from two double-blind, randomised controlled trials to model whole-brain effective connectivity (EC) data and compare it to the previously reported functional connectivity (FC) data gathered following LSD administration. LSD decreased brain connectivity and increased self-inhibition in certain brain regions. EC and FC offer promise as clinically-relevant biomarkers for LSD effects.
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 randomized, placebo-controlled, double-blind, cross-over trials, in which 45 participants were administered 100μg 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 widespread increases in interregional connectivity and reduced self-inhibition under LSD compared to placebo, with the notable exception of primarily decreased interregional connectivity and increased self-inhibition in occipital brain regions. This finding suggests that LSD perturbs the Excitation/Inhibition balance of the brain. Moreover, random forests classified LSD vs. placebo states based on FC and EC with comparably high accuracy (FC: 85.56%, EC: 91.11%) suggesting that both EC and FC are promising candidates for clinically-relevant biomarkers of LSD effects.