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Cited by 174Psychedelics and Drug StudiesFunctional Brain Connectivity StudiesHallucinations in medical conditions

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Altered network hub connectivity after acute LSD administration

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Müller, Felix, Dolder, Patrick C., Schmidt, André, Liechti, Matthias E., Borgwardt, Stefan·2018·NeuroImage: Clinical
DOI 10.1016/j.nicl.2018.03.005PMC PMC5857492
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Abstract

LSD is an ambiguous substance, said to mimic psychosis and to improve mental health in people suffering from anxiety and depression. Little is known about the neuronal correlates of altered states of consciousness induced by this substance. Limited previous studies indicated profound changes in functional connectivity of resting state networks after the administration of LSD. The current investigation attempts to replicate and extend those findings in an independent sample. In a double-blind, randomized, cross-over study, 100 μg LSD and placebo were orally administered to 20 healthy participants. Resting state brain activity was assessed by functional magnetic resonance imaging. Within -network and between -network connectivity measures of ten established resting state networks were compared between drug conditions. Complementary analysis were conducted using resting state networks as sources in seed-to-voxel analyses. Acute LSD administration significantly decreased functional connectivity within visual, sensorimotor and auditory networks and the default mode network. While between -network connectivity was widely increased and all investigated networks were affected to some extent, seed-to-voxel analyses consistently indicated increased connectivity between networks and subcortical (thalamus, striatum) and cortical (precuneus, anterior cingulate cortex) hub structures. These latter observations are consistent with findings on the importance of hubs in psychopathological states, especially in psychosis, and could underlay therapeutic effects of hallucinogens as proposed by a recent model.

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Crossref · 10.1016/j.nicl.2018.03.005

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Fig. 1 Between-condition differences in within-network functional connectivity. Only decreased connectivity (shown in blue-green) was observed for the contrast LSD > placebo. Results are overlayed on the corresponding resting state networks obtained in our analysis (yellow). Images are thresholded at p < 0.005 (two tailed), FWE (threshold free cluster enhancement). X, Y, and Z values indicate MNI coordinates. Right is the right side of the brain. (For interpretation of the references to color in this figure legend, the reader is referred to the online version of this chapter.)
Fig. 1 Between-condition differences in within-network functional connectivity. Only decreased connectivity (shown in blue-green) was observed for the contrast LSD > placebo. Results are overlayed on the corresponding resting state networks obtained in our analysis (yellow). Images are thresholded at p < 0.005 (two tailed), FWE (threshold free cluster enhancement). X, Y, and Z values indicate MNI coordinates. Right is the right side of the brain. (For interpretation of the references to color in this figure legend, the reader is referred to the online version of this chapter.)CC BY-NC-ND · PubMed Central
Fig. 2 Correlation matrix illustrating widespread increased functional connectivity between resting state networks under the drug condition compared to placebo. The colorbar indicates the t value, asterisks indicate significant differences (p < 0.05, FDR, two tailed). (For interpretation of the references to color in this figure legend, the reader is referred to the online version of this chapter.)
Fig. 2 Correlation matrix illustrating widespread increased functional connectivity between resting state networks under the drug condition compared to placebo. The colorbar indicates the t value, asterisks indicate significant differences (p < 0.05, FDR, two tailed). (For interpretation of the references to color in this figure legend, the reader is referred to the online version of this chapter.)CC BY-NC-ND · PubMed Central
Fig. 3 A: Results of seed-to-voxel analysis shown in Supplemental Fig. 4 combined in one map. The color bar indicates the number of converging components. B: Main effect of all ten resting state networks in seed-to-voxel analysis (cluster threshold p < 0.05, FDR, two tailed, cluster-forming threshold p < 0.001 uncorrected). Right is right side of the brain. (For interpretation of the references to color in this figure legend, the reader is referred to the online version of this chapter.)
Fig. 3 A: Results of seed-to-voxel analysis shown in Supplemental Fig. 4 combined in one map. The color bar indicates the number of converging components. B: Main effect of all ten resting state networks in seed-to-voxel analysis (cluster threshold p < 0.05, FDR, two tailed, cluster-forming threshold p < 0.001 uncorrected). Right is right side of the brain. (For interpretation of the references to color in this figure legend, the reader is referred to the online version of this chapter.)CC BY-NC-ND · PubMed Central
Fig. 4 Functional projections of resting state networks on striatal (left) and thalamic (right) structures. Only increases in FC were observed (cluster threshold p < 0.005, FDR, two tailed, cluster-forming threshold p < 0.001). Right is right side of the brain.
Fig. 4 Functional projections of resting state networks on striatal (left) and thalamic (right) structures. Only increases in FC were observed (cluster threshold p < 0.005, FDR, two tailed, cluster-forming threshold p < 0.001). Right is right side of the brain.CC BY-NC-ND · PubMed Central
Fig. 5 Comparison of the effects of hallucinogenic drugs on between-network connectivity obtained by another group (Carhart-Harris et al., 2016b; Roseman et al., 2014) and our results. All results on networks identified in the present study were included. Asterisks indicate significant differences between drug and placebo condition (green: Roseman et al., 2014; blue: Carhart-Harris et al., 2016b; red: present study). Black indicates networks which were not investigated. Roseman et al. reported separate results for two representation of the DMN, which were combined in this presentation. (For interpretation of the references to color in this figure legend, the reader is referred to the online version of this chapter.)
Fig. 5 Comparison of the effects of hallucinogenic drugs on between-network connectivity obtained by another group (Carhart-Harris et al., 2016b; Roseman et al., 2014) and our results. All results on networks identified in the present study were included. Asterisks indicate significant differences between drug and placebo condition (green: Roseman et al., 2014; blue: Carhart-Harris et al., 2016b; red: present study). Black indicates networks which were not investigated. Roseman et al. reported separate results for two representation of the DMN, which were combined in this presentation. (For interpretation of the references to color in this figure legend, the reader is referred to the online version of this chapter.)CC BY-NC-ND · PubMed Central

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Metadata

Authors
Müller, F., Dolder, P. C., Schmidt, A., Liechti, M. E., & Borgwardt, S.
Affiliations
University of Basel (CH)
Corresponding author
Borgwardt, Stefan
ORCID
Venue
NeuroImage: Clinical
Publisher
Elsevier BV
Published
2018
Volume
18
Pages
694-701
ISSN
2213-1582 (ISSN-L)
DOI
10.1016/j.nicl.2018.03.005
PMC
PMC5857492
OpenAlex
W2792211781
Cited by
174
References
61
Citations by year
2026: 15 · 2025: 21 · 2024: 23 · 2023: 45 · 2022: 22 · 2021: 19 · 2020: 19 · 2019: 6 · 2018: 4
FWCI
14.10
Type
journal article
Language
en
Open access
Licence
Locations
  • NeuroImage Clinical (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • edoc (University of Basel) (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • edoc (University of Basel)
Funders
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (320030_170249)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Hallucinations in medical conditions
Keywords
LSD, hallucinogens, resting-state functional connectivity, network hubs, default mode network, seed-to-voxel analysis, altered states of consciousness, psychosis, thalamus, striatum, precuneus, anterior cingulate cortex, visual network, sensorimotor network, auditory network
MeSH terms
Adult, Brain, Brain Mapping, Double-Blind Method, Female, Hallucinogens, Humans, Image Processing, Computer-Assisted, Lysergic Acid Diethylamide, Magnetic Resonance Imaging, Male, Middle Aged, Nerve Net, Cross-Over Studies

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