Modulation of long-term potentiation following microdoses of LSD captured by thalamo-cortical modelling in a randomised, controlled trial
dc.contributor.author | Murphy, RJ | |
dc.contributor.author | Godfrey, K | |
dc.contributor.author | Shaw, AD | |
dc.contributor.author | Muthukumaraswamy, S | |
dc.contributor.author | Sumner, RL | |
dc.date.accessioned | 2024-02-09T15:36:12Z | |
dc.date.issued | 2024-02-05 | |
dc.date.updated | 2024-02-09T15:28:10Z | |
dc.description.abstract | Background Microdosing psychedelics is a phenomenon with claimed cognitive benefts that are relatively untested clinically. Pre-clinically, psychedelics have demonstrated enhancing efects on neuroplasticity, which cannot be measured directly in humans, but may be indexed by non-invasive electroencephalography (EEG) paradigms. This study used a visual long-term potentiation (LTP) EEG paradigm to test the efects of microdosed lysergic acid diethylamide (LSD) on neural plasticity, both acutely while on the drug and cumulatively after microdosing every third day for six weeks. Healthy adult males (n=80) completed the visual LTP paradigm at baseline, 2.5 h following a dose of 10 µg of LSD or inactive placebo, and 6 weeks later after taking 14 repeated microdoses. Visually induced LTP was used as indirect index of neural plasticity. Surface level event-related potential (ERPs) based analyses are presented alongside dynamic causal modelling of the source localised data using a generative thalamocortical model (TCM) of visual cortex to elucidate underlying synaptic circuitry. Results Event-related potential (ERP) analyses of N1b and P2 components did not show evidence of changes in visually induced LTP by LSD either acutely or after 6 weeks of regular dosing. However modelling the complete timecourse of the ERP with the TCM demonstrated changes in laminar connectivity in primary visual cortex. This primarily included changes to self-gain and inhibitory input parameters acutely. Layer 2/3 to layer 5 excitatory connectivity was also diferent between LSD and placebo groups. After regular dosing only excitatory input from layer 2/3 into layer 5 and inhibitory input into layer 4 were diferent between groups. Conclusions Without modulation of the ERPs it is difcult to relate the fndings to other studies visually inducing LTP. It also indicates the classic peak analysis may not be sensitive enough to demonstrate evidence for changes in LTP plasticity in humans at such low doses. The TCM provides a more sensitive approach to assessing changes to plasticity as diferences in plasticity mediated laminar connectivity were found between the LSD and placebo groups. | en_GB |
dc.description.sponsorship | Health Research Council of New Zealand | en_GB |
dc.description.sponsorship | MindBio Therapeutics Ltd. | en_GB |
dc.identifier.citation | Vol. 25, No. 1, article 7 | en_GB |
dc.identifier.doi | https://doi.org/10.1186/s12868-024-00844-5 | |
dc.identifier.grantnumber | 20/845 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/135280 | |
dc.identifier | ORCID: 0000-0001-5741-7526 (Shaw, Alexander D) | |
dc.language.iso | en | en_GB |
dc.publisher | BMC | en_GB |
dc.relation.url | https://github.com/alexandershaw4/LTP_code | en_GB |
dc.rights | © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. | en_GB |
dc.subject | Long-term potentiation | en_GB |
dc.subject | Psychedelics | en_GB |
dc.subject | Neuroplasticity | en_GB |
dc.subject | Lysergic acid diethylamide | en_GB |
dc.subject | Dynamic causal modelling | en_GB |
dc.title | Modulation of long-term potentiation following microdoses of LSD captured by thalamo-cortical modelling in a randomised, controlled trial | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2024-02-09T15:36:12Z | |
exeter.article-number | 7 | |
dc.description | This is the final version. Available on open access from BMC via the DOI in this record. | en_GB |
dc.description | Data availability: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Code for the TCM model is available here: https://github.com/alexandershaw4/LTP_code. | en_GB |
dc.identifier.eissn | 1471-2202 | |
dc.identifier.journal | BMC Neuroscience | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2024-01-10 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2024-02-05 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2024-02-09T15:33:21Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2024-02-09T15:36:17Z | |
refterms.panel | A | en_GB |
refterms.dateFirstOnline | 2024-02-05 |
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mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.