Serotonergic psychedelic drugs LSD and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortex
Lysergic acid diethylamide (LSD) and psilocybin are serotonergic psychedelic compounds with potential in the treatment of mental health disorders. Past neuroimaging investigations have revealed that both compounds can elicit significant changes to whole-brain functional organization and dynamics. A...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-08-01
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| Series: | NeuroImage |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1053811922003445 |
| _version_ | 1811341101740589056 |
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| author | Manesh Girn Leor Roseman Boris Bernhardt Jonathan Smallwood Robin Carhart-Harris R. Nathan Spreng |
| author_facet | Manesh Girn Leor Roseman Boris Bernhardt Jonathan Smallwood Robin Carhart-Harris R. Nathan Spreng |
| author_sort | Manesh Girn |
| collection | DOAJ |
| description | Lysergic acid diethylamide (LSD) and psilocybin are serotonergic psychedelic compounds with potential in the treatment of mental health disorders. Past neuroimaging investigations have revealed that both compounds can elicit significant changes to whole-brain functional organization and dynamics. A recent proposal linked past findings into a unified model and hypothesized reduced whole-brain hierarchical organization as a key mechanism underlying the psychedelic state, but this has yet to be directly tested. We applied a non-linear dimensionality reduction technique previously used to map hierarchical connectivity gradients to assess cortical organization in the LSD and psilocybin state from two previously published pharmacological resting-state fMRI datasets (N = 15 and 9, respectively). Results supported our primary hypothesis: The principal gradient of cortical connectivity, describing a hierarchy from unimodal to transmodal cortex, was significantly flattened under both drugs relative to their respective placebo conditions. Between-condition contrasts revealed that this was driven by a reduction of functional differentiation at both hierarchical extremes – default and frontoparietal networks at the upper end, and somatomotor at the lower. Gradient-based connectivity mapping indicated that this was underpinned by a disruption of modular unimodal connectivity and increased unimodal-transmodal crosstalk. Results involving the second and third gradient, which, respectively represent axes of sensory and executive differentiation, also showed significant alterations across both drugs. These findings provide support for a recent mechanistic model of the psychedelic state relevant to therapeutic applications of psychedelics. More fundamentally, we provide the first evidence that macroscale connectivity gradients are sensitive to an acute pharmacological manipulation, supporting a role for psychedelics as scientific tools to perturb cortical functional organization. |
| first_indexed | 2024-04-13T18:51:43Z |
| format | Article |
| id | doaj.art-6181cb74918f4ac0959c183c78818ccf |
| institution | Directory Open Access Journal |
| issn | 1095-9572 |
| language | English |
| last_indexed | 2024-04-13T18:51:43Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage |
| spelling | doaj.art-6181cb74918f4ac0959c183c78818ccf2022-12-22T02:34:23ZengElsevierNeuroImage1095-95722022-08-01256119220Serotonergic psychedelic drugs LSD and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortexManesh Girn0Leor Roseman1Boris Bernhardt2Jonathan Smallwood3Robin Carhart-Harris4R. Nathan Spreng5Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 Rue Université, Montreal, QC H3A 2B4, Canada; Corresponding author.Centre for Psychedelic Research, Department of Brain Sciences, Imperial College London, London, United KingdomDepartment of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 Rue Université, Montreal, QC H3A 2B4, CanadaDepartment of Psychology, Queen's University, Kingston, ON, CanadaNeuroscape Psychedelics Division, Department of Neurology, University of California San Francisco, San Francisco, CA, United StatesDepartment of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 Rue Université, Montreal, QC H3A 2B4, Canada; Departments of Psychiatry and Psychology, McGill University, Montreal, QC, Canada; Douglas Mental Health University Institute, Verdun, QC, Canada; McConnell Brain Imaging Centre, McGill University, Montreal, QC, CanadaLysergic acid diethylamide (LSD) and psilocybin are serotonergic psychedelic compounds with potential in the treatment of mental health disorders. Past neuroimaging investigations have revealed that both compounds can elicit significant changes to whole-brain functional organization and dynamics. A recent proposal linked past findings into a unified model and hypothesized reduced whole-brain hierarchical organization as a key mechanism underlying the psychedelic state, but this has yet to be directly tested. We applied a non-linear dimensionality reduction technique previously used to map hierarchical connectivity gradients to assess cortical organization in the LSD and psilocybin state from two previously published pharmacological resting-state fMRI datasets (N = 15 and 9, respectively). Results supported our primary hypothesis: The principal gradient of cortical connectivity, describing a hierarchy from unimodal to transmodal cortex, was significantly flattened under both drugs relative to their respective placebo conditions. Between-condition contrasts revealed that this was driven by a reduction of functional differentiation at both hierarchical extremes – default and frontoparietal networks at the upper end, and somatomotor at the lower. Gradient-based connectivity mapping indicated that this was underpinned by a disruption of modular unimodal connectivity and increased unimodal-transmodal crosstalk. Results involving the second and third gradient, which, respectively represent axes of sensory and executive differentiation, also showed significant alterations across both drugs. These findings provide support for a recent mechanistic model of the psychedelic state relevant to therapeutic applications of psychedelics. More fundamentally, we provide the first evidence that macroscale connectivity gradients are sensitive to an acute pharmacological manipulation, supporting a role for psychedelics as scientific tools to perturb cortical functional organization.http://www.sciencedirect.com/science/article/pii/S1053811922003445 |
| spellingShingle | Manesh Girn Leor Roseman Boris Bernhardt Jonathan Smallwood Robin Carhart-Harris R. Nathan Spreng Serotonergic psychedelic drugs LSD and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortex NeuroImage |
| title | Serotonergic psychedelic drugs LSD and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortex |
| title_full | Serotonergic psychedelic drugs LSD and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortex |
| title_fullStr | Serotonergic psychedelic drugs LSD and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortex |
| title_full_unstemmed | Serotonergic psychedelic drugs LSD and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortex |
| title_short | Serotonergic psychedelic drugs LSD and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortex |
| title_sort | serotonergic psychedelic drugs lsd and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortex |
| url | http://www.sciencedirect.com/science/article/pii/S1053811922003445 |
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