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The widely accepted limbic-cortical dysregulation model has recently been extended by the concept of imbalanced reciprocal suppression between these 2 systems. This study investigates the refined theoretical framework. Neuroimaging datasets from 60 MDD and 60 healthy controls were obtained from the Canadian Biomarker Integration Network in Depression database, including structural magnetic resonance imaging (MRI) and resting-state functional MRI (rsfMRI). The cerebral cortex was parcellated using the modular analysis and similarity measurements (MOSI) technique. For each node, the average amplitude of low-frequency fluctuation (avgALFF) and nodal strength were calculated. Correlation analyses were conducted to establish an adjacency matrix and assess the relationship between nodal power and strength. The results indicated that the LM system in MDD displayed higher partition numbers and avgALFF (P\u2009&amp;lt;\u20090.005). A significant negative correlation between nodal strength and power was replicated (P\u2009&amp;lt;\u20091E-10), suggesting that greater functional input enhances regional neural suppression. Notably, MDD participants exhibited a higher negative correlation between FP nodal power and LM-FP connectivity (stronger suppression) but a lower negative correlation between LM nodal power and FP-LM connectivity (weaker suppression). These findings support the theory of abnormal cortical signal organization and reciprocal suppression in MDD.<\/jats:p>","DOI":"10.1093\/cercor\/bhaf089","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T10:16:26Z","timestamp":1743588986000},"source":"Crossref","is-referenced-by-count":6,"title":["Framing major depressive disorder as a condition of network imbalance at the compartment level: a proof-of-concept study"],"prefix":"10.1093","volume":"35","author":[{"given":"Tien-Wen","family":"Lee","sequence":"first","affiliation":[{"name":"The NeuroCognitive Institute (NCI) Clinical Research Foundation , 111 Howard Blvd., Suite 204, Mount Arlington, NJ 07856 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"key":"2025101402515360400_ref1","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.pscychresns.2006.11.002","article-title":"HPA axis dysfunction in unmedicated major depressive disorder and its normalization by pharmacotherapy correlates with alteration of neural activity in prefrontal cortex and limbic\/paralimbic regions","volume":"155","author":"Aihara","year":"2007","journal-title":"Psychiatry Res"},{"key":"2025101402515360400_ref2","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1146\/annurev.ne.09.030186.002041","article-title":"Parallel organization of functionally segregated circuits linking basal ganglia and cortex","volume":"9","author":"Alexander","year":"1986","journal-title":"Annu Rev Neurosci"},{"key":"2025101402515360400_ref3","doi-asserted-by":"crossref","DOI":"10.1176\/appi.books.9780890425596","volume-title":"Diagnostic and statistical manual of mental disorders","author":"American Psychiatric Association","year":"2013"},{"key":"2025101402515360400_ref4","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1002\/(SICI)1096-9861(19990920)412:2&lt;319::AID-CNE10&gt;3.0.CO;2-7","article-title":"Broc\u2019s region revisited: cytoarchitecture and intersubject variability","volume":"412","author":"Amunts","year":"1999","journal-title":"J Comp Neurol"},{"key":"2025101402515360400_ref5","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1038\/nrn2648","article-title":"Stress signalling pathways that impair prefrontal cortex structure and function","volume":"10","author":"Arnsten","year":"2009","journal-title":"Nat Rev Neurosci"},{"key":"2025101402515360400_ref6","doi-asserted-by":"publisher","first-page":"2269","DOI":"10.1093\/cercor\/bht195","article-title":"The neurobiology of thought: the groundbreaking discoveries of Patricia Goldman-Rakic 1937\u20132003","volume":"23","author":"Arnsten","year":"2013","journal-title":"Cereb Cortex"},{"key":"2025101402515360400_ref7","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.jad.2019.07.089","article-title":"Neuroimaging insights into the link between depression and insomnia: a systematic review","volume":"258","author":"Bagherzadeh-Azbari","year":"2019","journal-title":"J Affect Disord"},{"key":"2025101402515360400_ref8","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.jneumeth.2013.10.018","article-title":"The MVGC multivariate granger causality toolbox: a new approach to granger-causal inference","volume":"223","author":"Barnett","year":"2014","journal-title":"J Neurosci Methods"},{"key":"2025101402515360400_ref9","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1016\/j.jpsychires.2012.05.005","article-title":"Classifying responders and non-responders; 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