{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T07:08:54Z","timestamp":1778742534521,"version":"3.51.4"},"reference-count":44,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Levodopa (\n                      <jats:sc>l<\/jats:sc>\n                      \u2010dopa)\u2010induced dyskinesia (LID) is a common and difficult complication in Parkinson's disease (PD) patients. It may result from hyperactivation of the primary motor cortex (M1) due to hypoactivation of the basal ganglia (BG) output nuclei. Electrophysiological evidences are sparse, mainly due to technological limitations related to the poor ability to simultaneously acquire data from many neurons of the different involved regions. We exploited the Neuropixels technology to overcome these obstacles.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Extracellular Neuropixels recordings were acquired from awake head\u2010restrained mice in wild\u2010type (WT), parkinsonian, and LID conditions. Activity was recorded from M1 and the motor striatum simultaneously and compared for each mouse in four conditions: control (WT with and without\n                      <jats:sc>l<\/jats:sc>\n                      \u2010dopa), hemiparkinsonian (6\u2010hydroxydopamine model), and LID states.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Neural firing rates in M1 were decreased in PD and increased in LID as expected. Focusing on the quiet periods, the firing rates between the different conditions were similar. LID was associated with cortical intra\u2010layer hypersynchronization, a phenomenon not previously described. The overall synchrony was significantly increased between neurons of Layers 2, 3, and 5 in M1 in LID compared to PD state. Inter\u2010layer cross\u2010correlation was increased in LID, compared to PD state, between Layer 5 of M1 and the striatum. These changes in functional connectivity were absent in WT mice receiving\n                      <jats:sc>l<\/jats:sc>\n                      \u2010dopa.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our single\u2010cell recordings from thousands of neurons provide insight into cortical network changes in LID. We found that LID is associated with intra\u2010layer hypersynchronization of neurons within the motor cortex, which may be an intrinsic network feature within the cortico\u2013BG loop.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.70963","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T05:30:27Z","timestamp":1761024627000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cortical Intra\u2010Layer Hypersynchronization in Levodopa\u2010Induced Dyskinesia Mouse Model"],"prefix":"10.1002","volume":"15","author":[{"given":"Mohamed","family":"Khateb","sequence":"first","affiliation":[{"name":"Department of Neurology Rambam Medical Center  Haifa Israel"},{"name":"Department of Neurology University Health Network (UHN), University of Toronto  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fadi","family":"Aeed","sequence":"additional","affiliation":[{"name":"Department of Neurology Rambam Medical Center  Haifa Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shay","family":"Achvat","sequence":"additional","affiliation":[{"name":"Rappaport Faculty of Medicine Technion\u2010Israel Institute of Technology  Haifa Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaked","family":"Ron","sequence":"additional","affiliation":[{"name":"Rappaport Faculty of Medicine Technion\u2010Israel Institute of Technology  Haifa Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yitzhak","family":"Schiller","sequence":"additional","affiliation":[{"name":"Department of Neurology Rambam Medical Center  Haifa Israel"},{"name":"Rappaport Faculty of Medicine Technion\u2010Israel Institute of Technology  Haifa Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28538"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2016.10.006"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(16)30230\u20107"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27554"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnsys.2016.00026"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/35086062"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/124.3.546"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441\u2010004\u20100956\u20109"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0943\u201012.2012"},{"key":"e_1_2_9_11_1","doi-asserted-by":"crossref","unstructured":"Cenci M. A. andM.Lundblad.2007. \u201cRatings ofl\u2010DOPA\u2010Induced Dyskinesia in the Unilateral 6\u2010OHDA Lesion Model of Parkinson's Disease in Rats and Mice.\u201dCurrent Protocols in Neuroscience. 9.25. 1-9.25.23. Unit 9.25 supplement 41.https:\/\/doi.org\/10.1002\/0471142301.ns0925s41.","DOI":"10.1002\/0471142301.ns0925s41"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26378"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.baga.2013.12.001"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2015.11.009"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26947"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21475"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.01.017"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22\u201011\u201004639.2002"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1471\u20101931(00)00027\u20106"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28403"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3047\u201012.2012"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/124.3.558"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583\u2010019\u20100140\u20106"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4338\u201012.2013"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature24636"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26354"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21\u201018\u201007261.2001"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnsys.2021.713397"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11233736"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1080\/14740338.2019.1681966"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1318\u201016.2016"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.078758"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00701.2014"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583\u2010020\u20100315\u20101"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010neuro\u2010071013\u2010013916"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1471\u20101931(00)00031\u20108"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2011.05.021"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv312"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2022.114008"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2010.00142"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2017.00206"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2013.12.014"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1809983"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.614412"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.60.3.337"}],"container-title":["Brain and Behavior"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/brb3.70963","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/brb3.70963","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/brb3.70963","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T06:26:05Z","timestamp":1778739965000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/brb3.70963"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":44,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1002\/brb3.70963"],"URL":"https:\/\/doi.org\/10.1002\/brb3.70963","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/BRB3.70963\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.70963\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.70963\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.70963\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.70963\/v2\/review1","asserted-by":"object"}]},"ISSN":["2162-3279","2162-3279"],"issn-type":[{"value":"2162-3279","type":"print"},{"value":"2162-3279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"2024-12-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70963"}}