Psilocybin induces spatially constrained alterations in thalamic functional organizaton and connectivity
Background: Classic psychedelics, such as psilocybin and LSD, and other serotonin 2A receptor (5-HT2AR) agonists evoke acute alterations in perception and cognition. Altered thalamocortical connectivity has been hypothesized to underlie these effects, which is supported by some functional MRI (fMRI)...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | NeuroImage |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1053811922005511 |
| _version_ | 1811216370431426560 |
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| author | Andrew Gaddis Daniel E. Lidstone Mary Beth Nebel Roland R. Griffiths Stewart H. Mostofsky Amanda F. Mejia Frederick S. Barrett |
| author_facet | Andrew Gaddis Daniel E. Lidstone Mary Beth Nebel Roland R. Griffiths Stewart H. Mostofsky Amanda F. Mejia Frederick S. Barrett |
| author_sort | Andrew Gaddis |
| collection | DOAJ |
| description | Background: Classic psychedelics, such as psilocybin and LSD, and other serotonin 2A receptor (5-HT2AR) agonists evoke acute alterations in perception and cognition. Altered thalamocortical connectivity has been hypothesized to underlie these effects, which is supported by some functional MRI (fMRI) studies. These studies have treated the thalamus as a unitary structure, despite known differential 5-HT2AR expression and functional specificity of different intrathalamic nuclei. Independent Component Analysis (ICA) has been previously used to identify reliable group-level functional subdivisions of the thalamus from resting-state fMRI (rsfMRI) data. We build on these efforts with a novel data-maximizing ICA-based approach to examine psilocybin-induced changes in intrathalamic functional organization and thalamocortical connectivity in individual participants. Methods: Baseline rsfMRI data (n=38) from healthy individuals with a long-term meditation practice was utilized to generate a statistical template of thalamic functional subdivisions. This template was then applied in a novel ICA-based analysis of the acute effects of psilocybin on intra- and extra-thalamic functional organization and connectivity in follow-up scans from a subset of the same individuals (n=18). We examined correlations with subjective reports of drug effect and compared with a previously reported analytic approach (treating the thalamus as a single functional unit). Results: Several intrathalamic components showed significant psilocybin-induced alterations in spatial organization, with effects of psilocybin largely localized to the mediodorsal and pulvinar nuclei. The magnitude of changes in individual participants correlated with reported subjective effects. These components demonstrated predominant decreases in thalamocortical connectivity, largely with visual and default mode networks. Analysis in which the thalamus is treated as a singular unitary structure showed an overall numerical increase in thalamocortical connectivity, consistent with previous literature using this approach, but this increase did not reach statistical significance. Conclusions: We utilized a novel analytic approach to discover psilocybin-induced changes in intra- and extra-thalamic functional organization and connectivity of intrathalamic nuclei and cortical networks known to express the 5-HT2AR. These changes were not observed using whole-thalamus analyses, suggesting that psilocybin may cause widespread but modest increases in thalamocortical connectivity that are offset by strong focal decreases in functionally relevant intrathalamic nuclei. |
| first_indexed | 2024-04-12T06:37:54Z |
| format | Article |
| id | doaj.art-4999596387a644dfb67ab430169d6ad2 |
| institution | Directory Open Access Journal |
| issn | 1095-9572 |
| language | English |
| last_indexed | 2024-04-12T06:37:54Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage |
| spelling | doaj.art-4999596387a644dfb67ab430169d6ad22022-12-22T03:43:48ZengElsevierNeuroImage1095-95722022-10-01260119434Psilocybin induces spatially constrained alterations in thalamic functional organizaton and connectivityAndrew Gaddis0Daniel E. Lidstone1Mary Beth Nebel2Roland R. Griffiths3Stewart H. Mostofsky4Amanda F. Mejia5Frederick S. Barrett6Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Corresponding authors.Center for Neurodevelopmental and Imaging Research, Kennedy Krieger Institute, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USACenter for Neurodevelopmental and Imaging Research, Kennedy Krieger Institute, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, 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 21205, USADepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Center for Neurodevelopmental and Imaging Research, Kennedy Krieger Institute, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Statistics, Indiana University Bloomington, Bloomington, IN 47408, USADepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, 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 21205, USA; Department of Psychological and Brain Sciences, Johns Hopkins University, Baltimore, MD 21218, USA; Corresponding authors.Background: Classic psychedelics, such as psilocybin and LSD, and other serotonin 2A receptor (5-HT2AR) agonists evoke acute alterations in perception and cognition. Altered thalamocortical connectivity has been hypothesized to underlie these effects, which is supported by some functional MRI (fMRI) studies. These studies have treated the thalamus as a unitary structure, despite known differential 5-HT2AR expression and functional specificity of different intrathalamic nuclei. Independent Component Analysis (ICA) has been previously used to identify reliable group-level functional subdivisions of the thalamus from resting-state fMRI (rsfMRI) data. We build on these efforts with a novel data-maximizing ICA-based approach to examine psilocybin-induced changes in intrathalamic functional organization and thalamocortical connectivity in individual participants. Methods: Baseline rsfMRI data (n=38) from healthy individuals with a long-term meditation practice was utilized to generate a statistical template of thalamic functional subdivisions. This template was then applied in a novel ICA-based analysis of the acute effects of psilocybin on intra- and extra-thalamic functional organization and connectivity in follow-up scans from a subset of the same individuals (n=18). We examined correlations with subjective reports of drug effect and compared with a previously reported analytic approach (treating the thalamus as a single functional unit). Results: Several intrathalamic components showed significant psilocybin-induced alterations in spatial organization, with effects of psilocybin largely localized to the mediodorsal and pulvinar nuclei. The magnitude of changes in individual participants correlated with reported subjective effects. These components demonstrated predominant decreases in thalamocortical connectivity, largely with visual and default mode networks. Analysis in which the thalamus is treated as a singular unitary structure showed an overall numerical increase in thalamocortical connectivity, consistent with previous literature using this approach, but this increase did not reach statistical significance. Conclusions: We utilized a novel analytic approach to discover psilocybin-induced changes in intra- and extra-thalamic functional organization and connectivity of intrathalamic nuclei and cortical networks known to express the 5-HT2AR. These changes were not observed using whole-thalamus analyses, suggesting that psilocybin may cause widespread but modest increases in thalamocortical connectivity that are offset by strong focal decreases in functionally relevant intrathalamic nuclei.http://www.sciencedirect.com/science/article/pii/S1053811922005511Functional MRIFunctional connectivityIndependent component analysisResting statePsilocybinPsychedelics |
| spellingShingle | Andrew Gaddis Daniel E. Lidstone Mary Beth Nebel Roland R. Griffiths Stewart H. Mostofsky Amanda F. Mejia Frederick S. Barrett Psilocybin induces spatially constrained alterations in thalamic functional organizaton and connectivity NeuroImage Functional MRI Functional connectivity Independent component analysis Resting state Psilocybin Psychedelics |
| title | Psilocybin induces spatially constrained alterations in thalamic functional organizaton and connectivity |
| title_full | Psilocybin induces spatially constrained alterations in thalamic functional organizaton and connectivity |
| title_fullStr | Psilocybin induces spatially constrained alterations in thalamic functional organizaton and connectivity |
| title_full_unstemmed | Psilocybin induces spatially constrained alterations in thalamic functional organizaton and connectivity |
| title_short | Psilocybin induces spatially constrained alterations in thalamic functional organizaton and connectivity |
| title_sort | psilocybin induces spatially constrained alterations in thalamic functional organizaton and connectivity |
| topic | Functional MRI Functional connectivity Independent component analysis Resting state Psilocybin Psychedelics |
| url | http://www.sciencedirect.com/science/article/pii/S1053811922005511 |
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