{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:45:32Z","timestamp":1787791532248,"version":"build-2784847793"},"reference-count":161,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["U54HD104461"],"award-info":[{"award-number":["U54HD104461"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Auditory hypersensitivity is a well-established phenotype of Fragile X syndrome (FXS), but how it relates to neurobehavioral biomarkers remains poorly understood. To offer an integrated model, we propose a dual thalamic framework with hypo-lemniscal (LEM) and hyper-extralemniscal (EXLEM) thalamic models. Traditional FXS studies may have been conflating LEM and EXLEM systems, misrepresenting the origins of the hypersensitivity. We hypothesize that hyper-EXLEM pathology impacts FXS symptoms more. To test this hypothesis, we first review the dual thalamic systems and then demonstrate the hypo-LEM and hyper-EXLEM models in individuals with FXS. We use a 40\u00a0Hz auditory steady-state response (ie LEM responses) paradigm with relatively long (1.5 to 3\u00a0s) stimulus and interstimulus intervals to evoke N1\/P2 as Vertex Potentials (VPs, ie EXLEM responses) for onset and offset of the stimulus. We analyzed electroencephaogram (EEG) responses from 29 FXS and 33 healthy comparison individuals. Results showed lower intertrial coherence (ITC) in FXS, consistent with hypo-LEM predictions, and larger vertex potentials consistent with hyper-EXLEM predictions. Correlation analyses revealed that enhanced VPs classified FXS males more sensitively than ITC. These findings indicate that hyperreactivity of the EXLEM system is more dominantly related to FXS, which can provide a more accurate account for guiding diagnostic and therapeutic strategies.<\/jats:p>","DOI":"10.1093\/cercor\/bhaf141","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T07:38:24Z","timestamp":1750059504000},"source":"Crossref","is-referenced-by-count":9,"title":["Hyper-extralemniscal model of Fragile X syndrome"],"prefix":"10.1093","volume":"35","author":[{"given":"Makoto","family":"Miyakoshi","sequence":"first","affiliation":[{"name":"Division of Child and Adolescent Psychiatry, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH 45229 ,","place":["United States"]},{"name":"Department of Psychiatry, University of Cincinnati College of Medicine , Cincinnati, OH 45267 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeonseok","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Child and Adolescent Psychiatry, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH 45229 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A","family":"De Stefano","sequence":"additional","affiliation":[{"name":"Division of Child and Adolescent Psychiatry, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH 45229 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren M","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Phelan-McDermid Syndrome Foundation, Osprey , FL 34229 ,","place":["United States"]},{"name":"Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH 45229 ,","place":["United States"]},{"name":"Department of Pediatrics, University of Cincinnati College of Medicine , Cincinnati, OH 45229 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan E","family":"Norris","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Oklahoma; Norman , OK 73019 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren E","family":"Ethridge","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Oklahoma; Norman , OK 73019 ,","place":["United States"]},{"name":"Department of Pediatrics, Section of Developmental and Behavioral Pediatrics, University of Oklahoma Health Sciences Center; Oklahoma City , OK 73104 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig A","family":"Erickson","sequence":"additional","affiliation":[{"name":"Division of Child and Adolescent Psychiatry, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH 45229 ,","place":["United States"]},{"name":"Department of Psychiatry, University of Cincinnati College of Medicine , Cincinnati, OH 45267 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernest V","family":"Pedapati","sequence":"additional","affiliation":[{"name":"Division of Child and Adolescent Psychiatry, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH 45229 ,","place":["United States"]},{"name":"Department of Psychiatry, University of Cincinnati College of Medicine , Cincinnati, OH 45267 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,6,16]]},"reference":[{"key":"2025061603381789200_ref1","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1097\/00000542-196309000-00013","article-title":"Effects of thiopental on human cerebral evoked responses","volume":"24","author":"Abrahamian","year":"1963","journal-title":"Anesthesiology"},{"key":"2025061603381789200_ref2","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1152\/jn.1973.36.2.275","article-title":"Medial geniculate body of the cat: responses to tonal stimuli of neurons in medial division","volume":"36","author":"Aitkin","year":"1973","journal-title":"J Neurophysiol"},{"key":"2025061603381789200_ref3","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1007\/978-3-642-65438-1_14","volume-title":"Somatosensory system. 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