{"doi":"10.1101/2021.01.31.429016","title":"Transcriptomics-informed large-scale cortical model captures topography of pharmacological neuroimaging effects of LSD","abstract":"Abstract Psychoactive drugs can transiently perturb brain physiology while preserving brain structure. The role of physiological state in shaping neural function can therefore be investigated through neuroimaging of pharmacologically-induced effects. This paradigm has revealed that neural and experiential effects of lysergic acid diethylamide (LSD) are attributable to its agonist activity at the serotonin-2A receptor. Here, we integrate brainwide transcriptomics with biophysically-based large-scale circuit modeling to simulate acute neuromodulatory effects of LSD on human cortical dynamics. Our model captures the topographic effects of LSD-induced changes in cortical BOLD functional connectivity. These findings suggest that serotonin-2A-mediated modulation of pyramidal cell gain is the circuit mechanism through which LSD alters cortical functional topography. Individual-subject fitting reveals that the model captures patterns of individual neural differences in drug response that predict altered states of consciousness. This work establishes a framework for linking molecular-level manipulations to salient changes in brain function, with implications for precision medicine.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":214304,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9509,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":246746,"name":"Katrin H. Preller","orcid":"0000-0003-0413-7672","position":1,"is_corresponding":false},{"id":678684,"name":"Murat Demirtaş","orcid":"0000-0002-6035-7752","position":2,"is_corresponding":false},{"id":246748,"name":"Jie Lisa Ji","orcid":"0000-0002-6280-9070","position":3,"is_corresponding":false},{"id":55788,"name":"John H. Krystal","orcid":"0000-0001-6952-1726","position":4,"is_corresponding":false},{"id":246753,"name":"Franz X. Vollenweider","orcid":"0000-0001-9053-6164","position":5,"is_corresponding":false},{"id":225636,"name":"Alan Anticevic","orcid":"0000-0002-4324-0536","position":6,"is_corresponding":false},{"id":225637,"name":"John D. Murray","orcid":"0000-0003-4115-8181","position":7,"is_corresponding":false},{"id":225633,"name":"Joshua B. Burt","orcid":"0000-0002-5605-2091","position":0,"is_corresponding":true}],"reference_count":96,"raw_metadata":null,"created_at":"2026-07-18T23:52:46.604690Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}