{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:02:23Z","timestamp":1772118143263,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T00:00:00Z","timestamp":1737331200000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100020170","name":"Research Nova Scotia","doi-asserted-by":"publisher","award":["RNS\u2010NHIG\u20102021\u20101931"],"award-info":[{"award-number":["RNS\u2010NHIG\u20102021\u20101931"]}],"id":[{"id":"10.13039\/501100020170","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Patients with bipolar disorder (BD) demonstrate episodic memory deficits, which may be hippocampal\u2010dependent and may be attenuated in lithium responders. Induced pluripotent stem cell\u2013derived CA3 pyramidal cell\u2013like neurons show significant hyperexcitability in lithium\u2010responsive BD patients, while lithium nonresponders show marked variance in hyperexcitability. We hypothesize that this variable excitability will impair episodic memory recall, as assessed by cued retrieval (pattern completion) within a computational model of the hippocampal CA3.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We simulated pattern completion tasks using a computational model of the CA3 with different degrees of pyramidal cell excitability variance. Since pyramidal cell excitability variance naturally leads to a mix of hyperexcitability and hypoexcitability, we also examined what fraction (hyper\u2010 vs. hypoexcitable) was predominantly responsible for pattern completion errors in our model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Pyramidal cell excitability variance impaired pattern completion (linear model\n                      <jats:italic>\u03b2<\/jats:italic>\n                      = \u22122.00,\n                      <jats:italic>SE<\/jats:italic>\n                      = 0.03,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001). The effect was invariant to all other parameter settings in the model. Excitability variance, specifically hyperexcitability, increased the number of spuriously active neurons, increasing false alarm rates and producing pattern completion deficits. Excessive inhibition also induces pattern completion deficits by limiting the number of correctly active neurons during pattern retrieval.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Excitability variance in CA3 pyramidal cell\u2013like neurons observed in lithium nonresponders may predict pattern completion deficits in these patients. These cognitive deficits may not be fully corrected by medications that minimize excitability. Future studies should test our predictions by examining behavioral correlates of pattern completion in lithium\u2010responsive and \u2010nonresponsive BD patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.70209","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T11:30:16Z","timestamp":1737372616000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Impact of Electrophysiological Diversity on Pattern Completion in Lithium Nonresponsive Bipolar Disorder: A Computational Modeling Approach"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4955-9150","authenticated-orcid":false,"given":"Abraham","family":"Nunes","sequence":"first","affiliation":[{"name":"Department of Psychiatry Dalhousie University  Halifax Nova Scotia Canada"},{"name":"Faculty of Computer Science Dalhousie University  Halifax Nova Scotia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Selena","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Psychology, Neuroscience &amp; Behaviour McMaster University  Hamilton Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anouar","family":"Khayachi","sequence":"additional","affiliation":[{"name":"Montreal Neurological Institute, Department of Neurology &amp; Neurosurgery McGill University  Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shani","family":"Stern","sequence":"additional","affiliation":[{"name":"Sagol Department of Neurobiology, Faculty of Natural Sciences University of Haifa  Haifa Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Trappenberg","sequence":"additional","affiliation":[{"name":"Faculty of Computer Science Dalhousie University  Halifax Nova Scotia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Alda","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Dalhousie University  Halifax Nova Scotia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.books.9780890425596"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aap8757"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.1994.0019"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2013.10.005"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2017.12.057"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010021\u201001079\u20100"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386\u2010020\u20100683\u20102"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2016.08.002"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsycho.2015.10.013"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1319641111"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.66.1.22"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2007.03.003"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ypg.0000242194.36150.2b"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0893\u20106080(05)80042\u20105"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.25480"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399\u20105618.2007.00460.x"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.20103"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(15)00241\u2010X"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf1836"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00406\u2010020\u201001095\u20101"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.25249"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.8.2554"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/19585969.2022.2042164"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2010.175"},{"key":"e_1_2_9_26_1","unstructured":"Krotov D. andJ. J.Hopfield.2021. \u201cDense Associative Memory for Pattern Recognition.\u201d arXiv.http:\/\/arxiv.org\/abs\/1606.01164."},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145710001082"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.22561"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.1971.0078"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.20684"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166\u20102236(87)90011\u20107"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15526"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11552"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001218"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1151120"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1071795"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.11.017"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0501\u201011.2011"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1355617717000133"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2017.10"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnsys.2013.00074"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010020\u201000981\u20103"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2016.260"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2020.01.020"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2019.09.018"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci12040502"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbs062"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2010.09081187"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/bdi.13282"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031\u2010013\u20109956\u20100"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920\u20109964(01)00188\u20108"}],"container-title":["Brain and Behavior"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/brb3.70209","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T08:49:00Z","timestamp":1738140540000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/brb3.70209"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1002\/brb3.70209"],"URL":"https:\/\/doi.org\/10.1002\/brb3.70209","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/BRB3.70209\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.70209\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.70209\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.70209\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.70209\/v1\/review1","asserted-by":"object"}],"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.11.20.567781","asserted-by":"object"}]},"ISSN":["2162-3279","2162-3279"],"issn-type":[{"value":"2162-3279","type":"print"},{"value":"2162-3279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"2024-07-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70209"}}