Psilocybin acutely alters the functional connectivity of the claustrum with brain networks that support perception, memory, and attention

Frederick S. Barrett; Samuel R. Krimmel; Roland R. Griffiths; David A. Seminowicz; Brian N. Mathur

NeuroImage (Sep 2020)

Psilocybin acutely alters the functional connectivity of the claustrum with brain networks that support perception, memory, and attention

Frederick S. Barrett,
Samuel R. Krimmel,
Roland R. Griffiths,
David A. Seminowicz,
Brian N. Mathur

Affiliations

Frederick S. Barrett: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21224, USA; Center for Psychedelic and Consciousness Research, Johns Hopkins University School of Medicine, Baltimore, MD, 21224, USA; Corresponding author. Department of Psychiatry and Behavioral Sciences, Center for Psychedelic and Consciousness Research, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD, 21224, USA.
Samuel R. Krimmel: Department of Neural and Pain Sciences, School of Dentistry, and Center to Advance Chronic Pain Research, University of Maryland, Baltimore, MD, 21201, USA
Roland R. Griffiths: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21224, USA; Center for Psychedelic and Consciousness Research, Johns Hopkins University School of Medicine, Baltimore, MD, 21224, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21224, USA
David A. Seminowicz: Department of Neural and Pain Sciences, School of Dentistry, and Center to Advance Chronic Pain Research, University of Maryland, Baltimore, MD, 21201, USA
Brian N. Mathur: Department of Pharmacology, School of Medicine, University of Maryland, Baltimore, MD, 21201, USA

Journal volume & issue: Vol. 218
p. 116980

Abstract

Read online

Psychedelic drugs, including the serotonin 2a (5-HT2A) receptor partial agonist psilocybin, are receiving renewed attention for their possible efficacy in treating a variety of neuropsychiatric disorders. Psilocybin induces widespread dysregulation of cortical activity, but circuit-level mechanisms underlying this effect are unclear. The claustrum is a subcortical nucleus that highly expresses 5-HT2A receptors and provides glutamatergic inputs to arguably all areas of the cerebral cortex. We therefore tested the hypothesis that psilocybin modulates claustrum function in humans. Fifteen healthy participants (10M, 5F) completed this within-subjects study in which whole-brain resting-state blood-oxygenation level-dependent (BOLD) signal was measured 100 min after blinded oral administration of placebo and 10 mg/70 kg psilocybin. Left and right claustrum signal was isolated using small region confound correction. Psilocybin significantly decreased both the amplitude of low frequency fluctuations as well as the variance of BOLD signal in the left and right claustrum. Psilocybin also significantly decreased functional connectivity of the right claustrum with auditory and default mode networks (DMN), increased right claustrum connectivity with the fronto-parietal task control network (FPTC), and decreased left claustrum connectivity with the FPTC. DMN integrity was associated with right-claustrum connectivity with the DMN, while FPTC integrity and modularity were associated with right claustrum and left claustrum connectivity with the FPTC, respectively. Subjective effects of psilocybin predicted changes in the amplitude of low frequency fluctuations and the variance of BOLD signal in the left and right claustrum. Observed effects were specific to claustrum, compared to flanking regions of interest (the left and right insula and putamen). This study used a pharmacological intervention to provide the first empirical evidence in any species for a significant role of 5-HT2A receptor signaling in claustrum functioning, and supports a possible role of the claustrum in the subjective and therapeutic effects of psilocybin.

Published in NeuroImage

ISSN: 1053-8119 (Print); 1095-9572 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neuroimage

About the journal

Abstract

Keywords