Functional connectivity measures after psilocybin inform a novel hypothesis of early psychosis
This fMRI study (n=15) found increased functional connectivity (FC) between the default-mode network (DMN) and the task-positive network (TPN) under psilocybin, and suggests that psilocybin may be useful as a brain model for early psychosis.
Authors
- Robin Carhart-Harris
- David Nutt
- David Erritzoe
Published
Abstract
Psilocybin is a classic psychedelic and a candidate drug model of psychosis. This study measured the effects of psilocybin on resting-state network and thalamocortical functional connectivity (FC) using functional magnetic resonance imaging (fMRI). Fifteen healthy volunteers received intravenous infusions of psilocybin and placebo in 2 task-free resting-state scans. Primary analyses focused on changes in FC between the default-mode- (DMN) and task-positive network (TPN). Spontaneous activity in the DMN is orthogonal to spontaneous activity in the TPN, and it is well known that these networks support very different functions (ie, the DMN supports introspection, whereas the TPN supports externally focused attention). Here, independent components and seed-based FC analyses revealed increased DMN-TPN FC and so decreased DMN-TPN orthogonality after psilocybin. Increased DMN-TPN FC has been found in psychosis and meditatory states, which share some phenomenological similarities with the psychedelic state. Increased DMN-TPN FC has also been observed in sedation, as has decreased thalamocortical FC, but here we found preserved thalamocortical FC after psilocybin. Thus, we propose that thalamocortical FC may be related to arousal, whereas DMN-TPN FC is related to the separateness of internally and externally focused states. We suggest that this orthogonality is compromised in early psychosis, explaining similarities between its phenomenology and that of the psychedelic state and supporting the utility of psilocybin as a model of early psychosis.
Research Summary of 'Functional connectivity measures after psilocybin inform a novel hypothesis of early psychosis'
Introduction
Psilocybin is a classic tryptamine psychedelic and the prodrug of psilocin; it produces a range of subjective effects from mild perceptual changes to profound existential experiences. Functional MRI studies of spontaneous, task-free activity have established large-scale resting-state networks (RSNs) such as the default-mode network (DMN) and task-positive networks (TPNs). Previous work shows that DMN activity is associated with internally oriented cognition and that the DMN and TPNs are typically anti-correlated or orthogonal, a relationship thought to support the separation of introspective and externally focused mental states. Alterations in DMN-TPN coupling have been reported in clinical and pharmacological contexts, including increased DMN-TPN coupling in psychosis and with sedative anaesthesia, while thalamocortical coupling has been linked to arousal. Carhart-Harris and colleagues set out to test how psilocybin affects resting-state functional connectivity, focusing on two hypotheses: that psilocybin would increase coupling between the DMN and TPNs (reducing their normal orthogonality), and that thalamocortical connectivity would be preserved under psilocybin, distinguishing the psychedelic state from sedative states. By comparing psilocybin to placebo in healthy volunteers using complementary independent component analysis (ICA) and seed-based approaches, the study aimed to characterise between-network and thalamocortical connectivity changes and relate them to subjective effects.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
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- APA Citation
Carhart-Harris, R. L., Leech, R., Erritzoe, D., Williams, T. M., Stone, J. M., Evans, J., Sharp, D. J., Feilding, A., Wise, R. G., & Nutt, D. J. (2013). Functional connectivity measures after psilocybin inform a novel hypothesis of early psychosis. Schizophrenia Bulletin, 39(6), 1343-1351. https://doi.org/10.1093/schbul/sbs117
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