This trial re-analysis (n=15) found that LSD (75µg) produces significant changes in dorsolateral prefrontal cortex (DLPFC) functional connectivity that correlate with subjective experiences: ego dissolution was associated with increased connectivity between DLPFC, thalamus and visual processing areas, while emotional arousal correlated with connectivity between right DLPFC, intraparietal sulcus and salience network. MEG analysis revealed increased theta-band information flow between thalamus and DLPFC, supporting the theory that disrupted thalamic gating underlies ego dissolution.
Abstract of The Role of the Dorsolateral Prefrontal Cortex in Ego Dissolution and Emotional Arousal During the Psychedelic State
“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.“
Authors: Clayton R. Coleman, Kenneth Shinozuka, Robert Tromm, Ottavia Dipasquale, Mendel Kaelen, Leor Roseman, Suresh Muthukumaraswamy, David J. Nutt, Lionel Barnett & Robin L. Carhart-Harris
Summary of The Role of the Dorsolateral Prefrontal Cortex in Ego Dissolution and Emotional Arousal During the Psychedelic State
The authors begin by situating their research within the broader resurgence of interest in psychedelics as therapeutic agents, particularly LSD, which is being investigated for its efficacy in treating conditions such as generalised anxiety disorder and major depressive disorder. They highlight the role of the dorsolateral prefrontal cortex (DLPFC), a brain region implicated in mood regulation, executive function, and emotional processing. Previous studies using techniques such as transcranial magnetic stimulation (TMS) suggest that different hemispheres of the DLPFC contribute differently to mood disorders—left DLPFC is typically associated with depression, while the right DLPFC may be more relevant to mania and emotional arousal.
The study explores how LSD influences functional connectivity in the DLPFC during altered states of consciousness, particularly ego dissolution—a phenomenon in which individuals lose the sense of a separate self—and emotional arousal. These psychedelic experiences, while sometimes euphoric, can also resemble mania or early psychosis. The authors aim to clarify how left and right DLPFC connectivity correlates with self-reported experiences of ego dissolution, emotional arousal, and positive mood.
Methods
Participants and Study Design
Data were collected from 20 healthy volunteers, with 15 participants included in the final analysis. Participants underwent two sessions spaced at least 14 days apart—one involving an intravenous dose of LSD (75 µg) and the other a placebo. Each session involved resting-state functional MRI (fMRI) and magnetoencephalography (MEG) to measure brain activity. After each session, participants rated their subjective experiences using validated scales such as the Visual Analogue Scale (VAS) and the Altered States of Consciousness questionnaire.
Functional MRI Procedures
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https://doi.org/10.1002/hbm.70209
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Cite this paper (APA)
Coleman, C. R., Shinozuka, K., Tromm, R., Dipasquale, O., Kaelen, M., Roseman, L., ... & Carhart‐Harris, R. (2025). The Role of the Dorsolateral Prefrontal Cortex in Ego Dissolution and Emotional Arousal During the Psychedelic State. Human Brain Mapping, 46(5), e70209.
Study details
Topics studied
Neuroscience
Study characteristics
Original Re-analysis
Placebo-Controlled
Double-Blind
Within-Subject
Randomized
Re-analysis
Bio/Neuro
Participants
20
Humans
Compound Details
The psychedelics given at which dose and how many times
LSD 75 μg | 1xLinked Research Papers
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