{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T07:03:32Z","timestamp":1780124612668,"version":"3.54.0"},"reference-count":47,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100019155","name":"Nanjing Drum Tower Hospital","doi-asserted-by":"publisher","award":["RC2022\u2010023"],"award-info":[{"award-number":["RC2022\u2010023"]}],"id":[{"id":"10.13039\/501100019155","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81701675"],"award-info":[{"award-number":["81701675"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82202812"],"award-info":[{"award-number":["82202812"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82330059"],"award-info":[{"award-number":["82330059"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271965"],"award-info":[{"award-number":["82271965"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Amnestic mild cognitive impairment (aMCI) exhibits biased functional connectivity (FC) abnormalities impairing neural plasticity modulation. This study aimed to identify unbiased FC deficits using a brain\u2010wide association study (BWAS) and investigate repetitive transcranial magnetic stimulation (rTMS)\u2010driven plasticity restoration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>BWAS identified unbiased FC\u2010altered voxels (robustness\u2010validated). Region\u2010of\u2010interest (ROI)\u2010wise FC analysis localized disrupted circuits, which were modulated through precuneus\u2010targeted rTMS. Effective connectivity (EC) tested whether the precuneus exerted a causal influence on these disrupted circuits. Correlation analyses linked FC plasticity to cognitive and clinical outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Eleven brain regions with 31 altered unbiased FC circuits were robustly identified, centered on the bilateral anterior cingulate cortex (ACC). rTMS causally restored FC in the right supracallosal ACC and postcentral gyrus, correlating with improved information processing speed (IPS). Remarkably, 80.77% (21\/26) of aMCI responded clinically to rTMS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>This study first maps unbiased FC lesions in aMCI, confirming rTMS\u2010mediated ACC plasticity causally enhances IPS. These findings inform network\u2010targeted therapies to delay Alzheimer's disease (AD) progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>This is the first study to robustly map unbiased FC lesions in aMCI patients using a BWAS.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>rTMS causally restored FC in right supracallosal ACC in aMCI patients.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>FC and EC recovery demonstrated causal links to improvements in IPS and MoCA scores.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Remarkably, 80.77% (21\/26) of aMCI patients responded clinically to rTMS modulation.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70895","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T10:49:26Z","timestamp":1762858166000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Repetitive transcranial magnetic stimulation\u2010driven modulation of unbiased functional connectivity in the supracallosal anterior cingulate cortex causally ameliorates information processing speed in amnestic mild cognitive impairment"],"prefix":"10.1002","volume":"21","author":[{"given":"Jiu","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Radiology Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing University  Nanjing China"},{"name":"Institute of Medical Imaging and Artificial Intelligence Nanjing University  Nanjing China"},{"name":"Medical Imaging Center Nanjing Drum Tower Hospital Affiliated Hospital of Nanjing University Medical School  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Affiliated ZhongDa Hospital Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zigang","family":"Che","sequence":"additional","affiliation":[{"name":"Department of Radiology, School of Medicine Nanjing Tongren Hospital, Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology Affiliated Brain Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Radiology Affiliated Brain Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology Affiliated Brain Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhang","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Radiology Affiliated Brain Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjiao","family":"Huang","sequence":"additional","affiliation":[{"name":"Human Anatomy Experimental Training Center School of Basic Medicine Sciences Wannan Medical College  Wuhu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Human Biology University of Cape Town Faculty of Health Sciences  Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeming","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Radiology, School of Medicine Nanjing Tongren Hospital, Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiyun","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Radiology, School of Medicine Nanjing Tongren Hospital, Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Li","sequence":"additional","affiliation":[{"name":"Human Anatomy Experimental Training Center School of Basic Medicine Sciences Wannan Medical College  Wuhu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiology Affiliated Brain Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiology Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing University  Nanjing China"},{"name":"Institute of Medical Imaging and Artificial Intelligence Nanjing University  Nanjing China"},{"name":"Medical Imaging Center Nanjing Drum Tower Hospital Affiliated Hospital of Nanjing University Medical School  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1092852900016151"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.008"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11065-014-9249-6"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-210661"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-240368"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww255"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0152-6"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.media.2018.03.014"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv051"},{"key":"e_1_2_9_11_1","first-page":"436","article-title":"Brain\u2010wide analysis of functional connectivity in first\u2010episode and chronic stages of schizophrenia","volume":"43","author":"Li T","year":"2017","journal-title":"Schizophr Bull"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2024.1438260"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2013.12.009"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1162\/netn_a_00348"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.26251"},{"key":"e_1_2_9_16_1","first-page":"1314","article-title":"rTMS modulates precuneus\u2010hippocampal subregion circuit in patients with subjective cognitive decline","volume":"12","author":"Chen J","year":"2020","journal-title":"Aging (Albany NY)"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1301926"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2019.19090915"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2018.18040429"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2019.00307"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101883"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11682-019-00098-4"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2013.04.081"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.10.018"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.07.044"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.116189"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2017.12.048"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhaa160"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhy124"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2010.166"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2003.03034.x"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhy236"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhac070"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2022.118893"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-019-01945-2"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.26089"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.10.014"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-019-0212-7"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1440.011"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0060159"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3539-11.2011"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00338.2011"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2011.08.003"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3857"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0800005105"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1162\/netn_a_00261"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.01.026"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14130"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70895","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.70895","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70895","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T06:39:06Z","timestamp":1780123146000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.70895"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":47,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/alz.70895"],"URL":"https:\/\/doi.org\/10.1002\/alz.70895","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"2025-05-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70895"}}