Lysergic acid diethylamide-derived excitatory/ inhibitory ratio change enhances global synchrony in functional brain dynamics

Abstract

Lysergic acid diethylamide (LSD) has shown remarkable potential in modulating brain functional organization and dynamics. However, the exact mechanisms underlying its effects remain unclear. In this study, we employed a data-driven approach to analyze recurrent functional connectivity patterns in resting-state fMRI data and developed a parameterized feedback inhibition model to characterize excitatory/inhibitory (E/I) balance. The findings demonstrate that LSD enhances global brain synchrony and dynamic complexity. This enhanced synchrony likely stems from LSD’s preferential stabilization of a globally synchronized yet functionally non-modular brain state - a pattern showing higher occurrence probability and acts as an “attractor” that recruits transitions from cognitive control networks. Crucially, these phenomena appear underpinned by LSD-induced convergence of excitatory/inhibitory balance across cortical hierarchies, particularly through Sensorimotor (SOM) suppression coupled with transmodal potentiation, where the Sensorimotor cortices emerge as potential regulatory hubs driving this neurochemical rebalancing. These convergent effects are consistent with the emergence of a brain state characterized by weakened sensory anchoring and enhanced cognitive flexibility, where the typical separation between concrete perception and abstract cognition becomes blurred. This neurophysiological remodeling therefore suggests a potential mechanism that could contribute to LSD’s hallucinatory effects and its therapeutic potential in mental disorders characterized by rigid thought patterns.