LSD increases global brain synchrony and dynamic complexity by stabilizing a globally synchronized, functionally non-modular brain state that acts as an attractor, recruiting transitions from cognitive control networks. This enhanced synchrony arises from a convergence of excitatory/inhibitory balance across cortical hierarchies, driven by suppression in sensorimotor cortices and potentiation in transmodal regions. Sensorimotor cortices emerge as potential regulatory hubs for this rebalancing. The resulting brain state shows weakened sensory anchoring and enhanced cognitive flexibility, blurring the line between concrete perception and abstract cognition. This neurophysiological remodeling may underlie LSD's hallucinatory effects and its therapeutic potential for mental disorders with rigid thought patterns.
In a randomized controlled trial, 44 patients with treatment-resistant depression received either a one-hour inhalation of 50% nitrous oxide with 50% oxygen or a placebo of 50% oxygen with 50% air. Nitrous oxide treatment significantly altered the segregation of interconnected brain functional modules, as measured by EEG. The treatment showed superior antidepressant efficacy compared to placebo, with reductions in both the participation coefficient and connector hub after treatment. Changes in these modular metrics moderately correlated with reductions in depressive symptoms, offering insights into the neurophysiological mechanisms underlying nitrous oxide's rapid antidepressant effects.