{"doi":"10.1038/s42003-022-03395-9","title":"Neocortical localization and thalamocortical modulation of neuronal hyperexcitability contribute to Fragile X Syndrome","abstract":"Abstract Fragile X Syndrome (FXS) is a monogenetic form of intellectual disability and autism in which well-established knockout (KO) animal models point to neuronal hyperexcitability and abnormal gamma-frequency physiology as a basis for key disorder features. Translating these findings into patients may identify tractable treatment targets. Using source modeling of resting-state electroencephalography data, we report findings in FXS, including 1) increases in localized gamma activity, 2) pervasive changes of theta/alpha activity, indicative of disrupted thalamocortical modulation coupled with elevated gamma power, 3) stepwise moderation of low and high-frequency abnormalities based on female sex, and 4) relationship of this physiology to intellectual disability and neuropsychiatric symptoms. Our observations extend findings in Fmr1 −/− KO mice to patients with FXS and raise a key role for disrupted thalamocortical modulation in local hyperexcitability. This systems-level mechanism has received limited preclinical attention but has implications for understanding fundamental disease mechanisms.","journal":"Communications Biology","year":2022,"id":237225,"datarank":0.7905350898323333,"base_score":4.143134726391533,"endowment":4.143134726391533,"self_citation_contribution":0.62147020895873,"citation_network_contribution":0.16906488087360333,"self_endowment_contribution":0.62147020895873,"citer_contribution":0.16906488087360333,"corpus_percentile":null,"corpus_rank":null,"citation_count":62,"citer_count":15,"citers_with_citation_signal":10,"citers_with_endowment":10,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9573,"is_data_producer":true,"deposit_databanks":{"figshare":["10.6084/m9.figshare.19424015.v13"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":419702,"name":"Lauren Schmitt","orcid":"0000-0002-2864-3767","position":1,"is_corresponding":false},{"id":588980,"name":"Lauren E. Ethridge","orcid":"0000-0003-0601-6911","position":2,"is_corresponding":false},{"id":428833,"name":"Makoto Miyakoshi","orcid":"0000-0002-4062-6679","position":3,"is_corresponding":false},{"id":344413,"name":"John A. Sweeney","orcid":"0000-0003-1752-2828","position":4,"is_corresponding":false},{"id":654054,"name":"Rui Liu","orcid":"0000-0001-6602-808X","position":5,"is_corresponding":false},{"id":418815,"name":"Elizabeth G. Smith","orcid":"0000-0003-4661-0050","position":6,"is_corresponding":false},{"id":419701,"name":"Rebecca C. Shaffer","orcid":"0000-0001-6935-4403","position":7,"is_corresponding":false},{"id":294336,"name":"Kelli C. Dominick","orcid":"0000-0003-3775-2479","position":8,"is_corresponding":false},{"id":106044,"name":"Donald L. Gilbert","orcid":"0000-0002-9245-6878","position":9,"is_corresponding":false},{"id":713013,"name":"Steve W. Wu","orcid":"0000-0001-5102-174X","position":10,"is_corresponding":false},{"id":379425,"name":"Paul S. Horn","orcid":"0000-0002-4990-5754","position":11,"is_corresponding":false},{"id":278584,"name":"Devin K. Binder","orcid":"0000-0003-1597-5604","position":12,"is_corresponding":false},{"id":810168,"name":"Martine Lamy","orcid":"0000-0001-5873-0813","position":13,"is_corresponding":false},{"id":810754,"name":"Megan Axford","orcid":null,"position":14,"is_corresponding":false},{"id":294337,"name":"Craig A. Erickson","orcid":"0000-0003-4512-398X","position":15,"is_corresponding":false},{"id":419703,"name":"Ernest V. Pedapati","orcid":"0000-0002-7954-5104","position":0,"is_corresponding":true}],"reference_count":114,"raw_metadata":null,"created_at":"2026-07-19T00:22:08.925400Z","pmid":"35546357","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":[]}