Effective Connectivity in the CSTC Loop During Altered States of Consciousness
Poster No:
1234
Submission Type:
Abstract Submission
Authors:
Nikola Jajcay1, David Greguš2, Petr Adámek2, Jiří Horáček2, Jaroslav Hlinka1,2
Institutions:
1Institute of Computer Science, The Czech Academy of Sciences, Prague, Czech Republic, 2National Institute of Mental Health, Klecany, Czech Republic
First Author:
Co-Author(s):
Jaroslav Hlinka
Institute of Computer Science, The Czech Academy of Sciences|National Institute of Mental Health
Prague, Czech Republic|Klecany, Czech Republic
Institute of Computer Science, The Czech Academy of Sciences|National Institute of Mental Health
Prague, Czech Republic|Klecany, Czech Republic
Introduction:
Classic hallucinogens, or psychedelics, alter consciousness by modifying mood, perception, thought, and self-awareness. They offer a unique opportunity to explore perception, thought, and consciousness. The cortico–striato–thalamo-cortical model suggests that the thalamus plays a crucial role in managing information for the cortex, contributing to the regulation of consciousness. Variations in thalamic information gating can lead to an overload in the cortex, causing sensory flooding, cognitive disruptions, and ego dissolution. Schizophrenia patients show increased thalamus-to-cortical connectivity and deficits in preattentive sensorimotor gating after psychedelic administration. Pharmacological neuroimaging helps to understand how psychedelics influence CSTC loops. Psilocybin and psilocin, the primary psychedelic compounds, act as agonists at serotonergic 5-HT1A and 5-HT2A/C receptors, causing altered states of consciousness and making them ideal for investigating the effects of these states on effective connectivity during rest.
Methods:
This study is part of a broader clinical trial registered with EudraCT Number 2012-004579-37. The study was approved by the Ethical Committee of the National Institute of Mental Health (NIMH-CZ) and the State Institute for Drug Control. In summary, participants were recruited between November 2017 and July 2018 using a peer-to-peer approach. We analyzed 14 subjects (n=9 males and 5 females; mean age=37.1 years, range=28-49 years) across two experimental runs, separated by at least 28 days. In a double-blind, randomized, cross-over design, participants received either psilocybin (THC Pharm GmbH, >98% purity) or a placebo. Dosage was based on each participant's body weight, aiming for a target of 0.26 mg/kg. The drug was taken orally. Resting state MRI data were collected 100 minutes after treatment administration using a Siemens Magnetom Prisma 3T scanner, utilizing a GE-EPI sequence (52 slices; voxel size 3x3x3 mm; repetition time 2500 ms; echo time 30 ms; FOV 210 mm; flip angle 52°).
Results:
We analyzed each subject's neuronal dynamics using spectral dynamic causal modeling (sDCM), which models how neural populations affect fMRI time series, leading to functional connectivity measures. Following CTSC system principles, we examined the 4-node sDCM (thalamus, VS, PCC, temporal gyrus). We estimated DCM via spectral DCM, fitting the cross-spectral density with a power-law model of neuronal fluctuations. Our preliminary analysis, aligned with Preller, 2019, concatenated time series across subjects and modeled the contrast |psilocybin > placebo|. We evaluated model comparisons (free energy) with and without each effect to estimate posterior probabilities for each model (using the PEB). Our results show that psilocybin administration increased effective connectivity from the thalamus to the VS and the PCC to the VS. Moreover, psilocybin decreased effective connectivity between the following regions: thalamus to the Temp, VS to the thalamus, PCC to the Temp, and Temp to the VS, and self-inhibition within the thalamus.
·The CSTC network architecture with color-coded effective connectivity changes between placebo and psilocybin.
·The |psilocybin > placebo| contrast connectivity changes estimated using PEB.
Conclusions:
The current results support the predictions outlined in the CSTC model and provide evidence that psychedelics alter the functional connectivity within the CSTC pathways that play a role in regulating sensory and sensorimotor information flow to the cortex. In particular, psilocybin diminishes the striatum's influence on the thalamus, effectively loosening the thalamic filter, but does so selectively for some areas of the cortex. Notably, the findings emphasize the role of the thalamus–PCC connection in facilitating the effects of psychedelics.
The study was supported by ERDF-Project Brain dynamics No. CZ.02.01.01/00/22_008/0004643.
The study was supported by ERDF-Project Brain dynamics No. CZ.02.01.01/00/22_008/0004643.
Modeling and Analysis Methods:
Bayesian Modeling 2
Connectivity (eg. functional, effective, structural) 1
fMRI Connectivity and Network Modeling
Perception, Attention and Motor Behavior:
Consciousness and Awareness
Keywords:
Consciousness
FUNCTIONAL MRI
Seretonin
Other - Psilocybin
1|2Indicates the priority used for review
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Provide references using APA citation style.
Vollenweider, F. X., & Geyer, M. A. (2001). A systems model of altered consciousness: integrating natural and drug-induced psychoses. Brain research bulletin, 56(5), 495-507.
Preller, K. H., Razi, A., Zeidman, P., Stämpfli, P., Friston, K. J., & Vollenweider, F. X. (2019). Effective connectivity changes in LSD-induced altered states of consciousness in humans. Proceedings of the National Academy of Sciences, 116(7), 2743-2748.