{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T09:03:19Z","timestamp":1789549399013,"version":"build-2803163510"},"reference-count":81,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Fragile X syndrome (FXS) is the most common inherited form of intellectual disability and autism spectrum disorder. Previous studies in the\n                      <jats:italic>Fmr1<\/jats:italic>\n                      knockout (KO) mouse model of FXS and affected individuals have identified common electroencephalographic (EEG) abnormalities, which constitute biomarkers of cortical dysfunction for drug treatments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We evaluated the effects of three different doses of oral blarcamesine, a Sigma-1 receptor agonist (S1R), on FXS-relevant EEG biomarkers in\n                      <jats:italic>Fmr1<\/jats:italic>\n                      KO mice utilizing a multielectrode array (MEA) on resting-state power (from delta to gamma frequencies) and network synchronization (inter-trial phase coherence [ITPC]) using three auditory stimulation paradigms (chirp, auditory steady-state response [ASSR] at 40\u00a0Hz and at 80\u00a0Hz).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Blarcamesine-treated\n                      <jats:italic>Fmr1<\/jats:italic>\n                      KO mice showed dose-dependent modulation of EEG biomarkers across cortical regions. Resting-state EEG power was reduced across multiple frequency bands, including suppression of the FXS-distinctive elevation in the gamma band. Significant improvements in ITPC were observed in all cortical regions for chirp stimulation and 40\u00a0Hz ASSR, while modest improvements were seen for 80\u00a0Hz ASSR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Altogether, these data demonstrate that blarcamesine modulates multiple EEG biomarkers of cortical dysfunction in\n                      <jats:italic>Fmr1<\/jats:italic>\n                      KO mice. Given that these biomarkers are associated with fundamental neurophysiological mechanisms underlying cognitive and behavioral abnormalities, and are shared between FXS mouse models and affected individuals, these findings are consistent with previously characterized S1R-mediated pharmacological effects of blarcamesine. These data support further investigation of blarcamesine\u2019s clinical potential in FXS and other neurodevelopmental disorders.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1786406","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T08:07:35Z","timestamp":1789546055000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Blarcamesine improves EEG biomarkers of cortical dysfunction in a mouse model of fragile X syndrome"],"prefix":"10.3389","volume":"17","author":[{"given":"Carrie R.","family":"Jonak","sequence":"first","affiliation":[{"name":"Division of Biomedical Sciences, School of Medicine, University of California","place":["Riverside, CA, United States"]},{"name":"Neuroscience Graduate Program, University of California","place":["Riverside, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha A.","family":"Assad","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, School of Medicine, University of California","place":["Riverside, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devin K.","family":"Binder","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, School of Medicine, University of California","place":["Riverside, CA, United States"]},{"name":"Neuroscience Graduate Program, University of California","place":["Riverside, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Tran","sequence":"additional","affiliation":[{"name":"Anavex Life Sciences Corp.","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher U.","family":"Missling","sequence":"additional","affiliation":[{"name":"Anavex Life Sciences Corp.","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter E.","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Emory University School of Medicine","place":["Atlanta, GA, United States"]},{"name":"Department of Neurology, Boston Children\u2019s Hospital","place":["Boston, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1159\/000013817","article-title":"Reliability of 80-Hz amplitude-modulation-following response detected by phase coherence","volume":"4","author":"Aoyagi","year":"1999","journal-title":"Audiol. 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