Lysergic acid diethylamide-derived excitatory/inhibitory ratio change enhances global synchrony in functional brain dynamics
Lingyu Zhang, Weiyang Shi, Ziyang Zhao, Ziyi Wang, Congying Chu, Bokai Zhao, Jiaqi Zhang, Qianhui Liu, Yueheng Lan, Tianzi Jiang
PLoS Computational Biology December 15, 2025 DOI: 10.1371/journal.pcbi.1013822 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Human participants (resting-state fMRI data) |
| Intervention | Lysergic acid diethylamide (LSD) |
| Topics | LSD |
| Keywords | Neurochemical Cognition Neurophysiology Mechanism biology Perception Human brain Sensory system Electroencephalography Dynamics music Functional integration Brain mapping Resting State FMRI |
| Key findings | LSD enhances global brain synchrony and dynamic complexity by stabilizing a globally synchronized brain state through convergence of excitatory/inhibitory balance across cortical hierarchies. |
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.
Comparable studies
Other observational and cohort studies on LSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution. Human participants | 2016 | Observational cohort | |
| Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin Humans | 2017 | Observational study | |
| Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. USA adult respondents from the National Survey on Drug Use and Health (2008-2012) | 2015 | Observational cohort | n = 190,000 |
| Psychedelics not linked to mental health problems or suicidal behavior: A population study Randomly selected United States adults | 2015 | Observational cohort | n = 135,095 |
| Whole-Brain Multimodal Neuroimaging Model Using Serotonin Receptor Maps Explains Non-linear Functional Effects of LSD. Healthy human participants | 2018 | Observational study with computational modeling |
Citations in the library
Cites 26
- Experience sampling during fMRI reveals default network and executive system contributions to mind wandering. Proceedings of the National Academy of Sciences May 26, 2009
- Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction Journal of Psychopharmacology September 11, 2014
- Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences April 11, 2016
- Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution. Current Biology April 13, 2016
- The Psychedelic State Induced by Ayahuasca Modulates the Activity and Connectivity of the Default Mode Network PLoS One February 18, 2015
and 21 more in the library