The Role of the Dorsolateral Prefrontal Cortex in Ego Dissolution and Emotional Arousal During the Psychedelic State.
Clayton R. Coleman, Kenneth Shinozuka, Robert Tromm, Ottavia Dipasquale, Mendel Kaelen, Leor Roseman, Suresh Muthukumaraswamy, David Nutt, Lionel Barnett, Robin Carhart-Harris
Human Brain Mapping April 1, 2025 DOI: 10.1002/hbm.70209 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Healthy human participants |
| Intervention | Lysergic acid diethylamide (LSD) |
| Topics | Ego dissolution |
| Keywords | Psychedelics Consciousness Brain-imaging Altered-states |
| Citations | 4 |
| Key findings | LSD increases functional connectivity between the DLPFC, thalamus, and visual areas, which correlates with ego dissolution and emotional arousal. |
Abstract
Lysergic acid diethylamide (LSD) is a classic serotonergic psychedelic that induces a profoundly altered conscious state. In conjunction with psychological support, it is currently being explored as a treatment for generalized anxiety disorder and depression. The dorsolateral prefrontal cortex (DLPFC) is a brain region that is known to be involved in mood regulation and disorders; hypofunction in the left DLPFC is associated with depression. This study investigated the role of the DLPFC in the psycho-emotional effects of LSD with functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) data of healthy human participants during the acute LSD experience. In the fMRI data, we measured the correlation between changes in resting-state functional connectivity (RSFC) of the DLPFC and post-scan subjective ratings of positive mood, emotional arousal, and ego dissolution. We found significant, positive correlations between ego dissolution and functional connectivity between the left & right DLPFC, thalamus, and a higher-order visual area, the fusiform face area (FFA). Additionally, emotional arousal was significantly associated with increased connectivity between the right DLPFC, intraparietal sulcus (IPS), and the salience network (SN). A confirmational "reverse" analysis, in which the outputs of the original RSFC analysis were used as input seeds, substantiated the role of the right DLPFC and the aforementioned regions in both ego dissolution and emotional arousal. Subsequently, we measured the effects of LSD on directed functional connectivity in MEG data that was source-localized to the input and output regions of both the original and reverse analyses. The Granger causality (GC) analysis revealed that LSD increased information flow between two nodes of the 'ego dissolution network', the thalamus and the DLPFC, in the theta band, substantiating the hypothesis that disruptions in thalamic gating underlie the experience of ego dissolution. Overall, this multimodal study elucidates a role for the DLPFC in LSD-induced states of consciousness and sheds more light on the brain basis of ego dissolution.
Comparable studies
Other observational and cohort studies on ego dissolution, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution. Human participants | 2016 | Observational cohort | |
| Sub-acute and long-term effects of ayahuasca on affect and cognitive thinking style and their association with ego dissolution Non-pathological ayahuasca ceremony attendees in the Netherlands and Colombia | 2018 | Observational cohort | n = 57 |
| From Egoism to Ecoism: Psychedelics Increase Nature Relatedness in a State-Mediated and Context-Dependent Manner. Individuals planning to use a psychedelic | 2019 | Prospective online study | n = 654 |
| Neural and subjective effects of inhaled N,N-dimethyltryptamine in natural settings. Healthy and experienced participants | 2021 | Observational field study | n = 35 |
| Mystical and Ego-Dissolution Experiences in Ayahuasca and Jurema Holistic Rituals: An Exploratory Study Participants in ayahuasca and jurema rituals in a natural environment | 2023 | Observational study | n = 26 |
Citations in the library
Cited by 2
- Psychedelic experiences elicited by serotonergic psychedelics: Molecular mechanisms and functional connectivity changes in the brain Neuroscience & Biobehavioral Reviews December 16, 2025
- Psychedelic Modulation of Excitation/Inhibition Balance: A Dual-Phase Neurodevelopmental Model. ACS Chemical Neuroscience January 7, 2026
Cites 49
- Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. American Journal of Psychiatry 2003
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences April 11, 2016
and 44 more in the library