Psilocybin acutely alters the functional connectivity of the claustrum with brain networks that support perception, memory, and attention
This double-blind, placebo-controlled, within-subject study (n=15) of psilocybin (10mg/70kg) in healthy participants looked specifically at the claustrum and found many changes in the connectiveness to other parts of the brain.
Authors
- Roland Griffiths
- Frederick Barrett
Published
Abstract
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.
Research Summary of 'Psilocybin acutely alters the functional connectivity of the claustrum with brain networks that support perception, memory, and attention'
Introduction
Classic serotonergic psychedelic drugs such as psilocybin acutely alter sensory perception and executive function and are being revisited for potential therapeutic value across neuropsychiatric disorders. Previous imaging studies indicate that psilocybin perturbs the integrity and coupling of large-scale networks such as the default mode network (DMN) and task-positive/executive networks, but the circuit-level mechanisms underlying these effects remain unclear. The claustrum, a subcortical telencephalic nucleus with high expression of 5-HT2A receptors and widespread glutamatergic projections to cortex, is a plausible target mediating psilocybin’s broad cortical effects; prior human imaging has linked the claustrum to task onset and network switching distinct from neighbouring structures like the insula and putamen. Barrett and colleagues therefore tested the hypothesis that psilocybin modulates claustrum function in humans. Using resting-state fMRI in a blinded, within-subject design, the study compared measures of claustrum activity (variance and amplitude of low-frequency BOLD fluctuations) and claustrum functional connectivity with canonical cortical networks after oral placebo and after a moderate dose of psilocybin (10 mg/70 kg). The investigators also examined relationships between claustrum metrics, network integrity/modularity, and contemporaneous subjective effects.
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Study Details
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- APA Citation
Barrett, F. S., Krimmel, S. R., Griffiths, R. R., Seminowicz, D. A., & Mathur, B. N. (2020). Psilocybin acutely alters the functional connectivity of the claustrum with brain networks that support perception, memory, and attention. NeuroImage, 218, 116980. https://doi.org/10.1016/j.neuroimage.2020.116980
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