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Using data-driven connectivity-based parcellation on 158 first-episode medication-naïve non-comorbid MDD patients and 152 healthy controls, the ACC was divided into bilateral ventral and dorsal subregions. Diagnosis-by-subregion effects were strongest in default mode network areas, with ventral ACC–DMN hypoconnectivity in MDD and links to core depressive symptoms and maladaptive behaviors.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/symptom-specific-alterations-in-subregional-intrinsic-connectivity-of-anterior-cingulate-cortex-in-major-depressive-disorder/459806/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/symptom-specific-alterations-in-subregional-intrinsic-connectivity-of-anterior-cingulate-cortex-in-major-depressive-disorder/459806.png","ImageObject",300,407,{"name":92,"@type":93},"Chumphorn","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-02","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What was the main goal of this study?","Question",{"text":112,"@type":113},"To characterize how ACC subregional intrinsic connectivity is altered in MDD and determine how these changes relate to clinical features.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were ACC subregions defined in the analysis?",{"text":117,"@type":113},"The study used data-driven connectivity-based parcellation (CBP) to delineate optimal ACC functional partitions, resulting in bilateral ventral and dorsal ACC subregions.",{"name":119,"@type":110,"acceptedAnswer":120},"Which brain networks showed the strongest diagnostic differences?",{"text":121,"@type":113},"Significant diagnosis-by-subregion interactions were mainly observed in default mode network (DMN) regions, including reduced vACC–DMN connectivity in MDD.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},459806,1791331831,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},2336475401981,"https://ap-avatar.wpscdn.com/avatar/22000c94efd8d5204d?x-image-process=image/resize,m_fixed,w_180,h_180&k=1786935347598174694","Translational [Psychiatry](Psychiatry www.nature.com/tp)[ www.nature.com/tp](Psychiatry www.nature.com/tp)  \nARTICLE OPEN   \nSymptom-specific alterations in subregional intrinsic connectivity of anterior cingulate cortex in major depressive disorder  \nZilin Zhou1,2, Lianqing Zhang 1, Xinyue Hu1,2, Lingxiao Cao1, Yingxue Gao1,2, Hailong Li1, Weijie Bao 1, Mengyue Tang 1, Huaiqiang Sun1,2, Weihong Kuang3,4, Graham J. Kemp5, Xiaoqi Huang 1,4 ✉ and Qiyong Gong 1,4  \n© The Author(s) 2025  \n\n|  |  |  |  |  |  |\n| --- | --- | --- | --- | --- | --- |\n|  | The anterior cingulate cortex (ACC) is critically implicated in major depressive disorder (MDD), with distinct subregional dysfunctions related to specific aspects of emotional and cognitive dysregulation. However, its precise functional architecture, including the number, boundaries and intrinsic connectivity patterns of subdivisions, remains to be characterized in MDD. To address this, we employed data-driven connectivity-based parcellation (CBP) to delineate the optimal ACC functional partitions in 158 first-episode medication-naïve non-comorbid patients with MDD, and 152 healthy controls (HC) . We generated subregionspecific ACC intrinsic connectivity maps, and analyzed group differences using diagnosis-by-subregion flexible factorial analyses of variance. We further explored the relationship between connectivity changes and clinical features. The ACC was optimally parcellated into bilateral ventral ACC (vACC) and dorsal ACC (dACC): The vACC showed preferential connections with default mode network (DMN) regions, whereas the dACC primarily connected to salience network and subcortical areas. Significant diagnosis-bysubregion interactions in ACC connectivity were mainly in the DMN regions: in HC, vACC showed stronger connectivity with DMN regions compared to the dACC, while this difference was attenuated in MDD, characterized by the vACC-DMN hypoconnectivity and a trend towards dACC-DMN hyperconnectivity. Clinically, lower vACC-DMN connectivity was related with core depressive symptoms, i.e., lower mood and longer illness duration, while higher dACC-DMN connectivity was linked to elevated maladaptive behaviors, e.g., suicide and insomnia. These findings confirm ventral-dorsal functional heterogeneity of ACC architecture and reveal symptom-specific patterns of subregional ACC-DMN dysconnectivity in MDD, which may provide insights for developing tailored interventions to address specific clinical manifestations. |  |  |  |  |\n|  |  |  |  |  |  |\n|  |  |  |  |  |  |\n|  |  |  |  |  |  |\n|  |  |  |  |  |  |\n|  |  |  |  |  |  |\n|  |  |  |  |  |  |\n|  |  |  |  |  |  |\n|  |  |  |  |  |  |\n|  |  |  |  |  |  |\n|  |  |  |  |  |  |\n|  |  |  |  |  |  |\n|  |  |  |  |  |  |\n|  |  |  |  |  |  |\n|  |  |  |  |  |  |\n|  |  |  |  |  |  |\n|  | Translational Psychiatry (2026)16:7; [https://doi.org/10.1038/s41398-025-03758-w](https://doi.org/10.1038/s41398-025-03758-w) |  |  |  |  |\n|  |  |  |  |  |  |\n\nINTRODUCTION  \nThe anterior cingulate cortex (ACC) is a brain structure crucial for emotional processing, cognitive regulation, and homeostatic maintenance [1, 2] . Dysfunction of ACC has been strongly associated with stress-related negative emotions, anhedonia-like behaviors, ruminations, and cognitive deficits [3–6], which are commonly observed in major depressive disorder (MDD) . Consequently, the ACC is increasingly recognized to play a pivotal role in the pathophysiology of MDD and the mechanisms underlying antidepressant treatments [7–9] .  \nAn early cellular-level study identified reduced neuronal soma size and enhanced neuronal density in cortical layers 5 and 6 of the ACC as key pathological features of MDD [10] . On the macrostructural level, meta-analyses and multicenter studies in MDD reported smaller gray matter volume and thinner cortical thickness in the ACC [11, 12] . Functional neuroimaging studies in MDD revealed abnormal ACC activation at rest and during tasks  \nconcerning negative emotion and req","cbCaiekGuu8A9QgD","https://ap.wps.com/l/cbCaiekGuu8A9QgD","pdf",2145674,11,"English","# Introduction\n## Anterior cingulate cortex in MDD\n## Prior structural and functional evidence\n## Connectivity studies and ventral-dorsal heterogeneity\n## Study rationale and objectives","[{\"question\":\"What was the main goal of this study?\",\"answer\":\"To characterize how ACC subregional intrinsic connectivity is altered in MDD and determine how these changes relate to clinical features.\"},{\"question\":\"How were ACC subregions defined in the analysis?\",\"answer\":\"The study used data-driven connectivity-based parcellation (CBP) to delineate optimal ACC functional partitions, resulting in bilateral ventral and dorsal ACC subregions.\"},{\"question\":\"Which brain networks showed the strongest diagnostic differences?\",\"answer\":\"Significant diagnosis-by-subregion interactions were mainly observed in default mode network (DMN) regions, including reduced vACC–DMN connectivity in MDD.\"}]","Symptom-specific alterations in subregional intrinsic connectivity of anterior cingulate cortex in major depressive disorder | PDF",1790756937,28]