Differences in the Efficacy of Cognitive Function Treatment Related to Functional Patterns in the Frontal-Limbic Network in Patients With Bipolar Disorder

Sep 29, 2026

Background: Identify neurobiomarkers predicting cognitive-treatment efficacy in patients with bipolar disorder (BD). Methods: Analyze regional homogeneity (ReHo) and degree centrality (DC) from functional MRI to compare BD patients with healthy controls, and apply connectome-based predictive modeling to link baseline measures to delayed memory. Results: BD (N=92) shows increased activity in right hippocampus/parahippocampal gyrus, reduced left middle frontal gyrus ReHo/DC, and cognition-improvement (n=24) associates with baseline right superior temporal gyrus and left anterior cingulate cortex; support vector machine distinguishes improvement patterns. Conclusions: Abnormal frontal-limbic network activity underlies cognitive impairment, with right STG and left ACC as candidate neurobiomarkers and targets for future physical interventions.

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Introduction

Regional homogeneity and degree centrality in bipolar disorder

Need for neural-circuit biomarkers and cognition trials

CNS Neuroscience & Therapeutics ORIGINAL ARTICLE OPEN ACCESS Differences in the Efficacy of Cognitive Function Treatment Related to Functional Patterns in the Frontal-Limbic Network in Patients With Bipolar Disorder Sujuan Li1 | Yangpan Ou1 | Haiping Liu2 | Qianyu Dong1 | Yan Qiu3 | Ziwei Teng4 | Hui Tang1 | Hui Xiang1 | Guowei Wu1 | Jindong Chen1 | Bolun Wang5 | Lutao Jiang6 | Haishan Wu1,6 1Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China | 2Qingdao Mental Health Center, Qingdao, Shandong, China | 3Xiamen Xianyue Hospital, Xianyue Hospital Affiliated With Xiamen Medical College, Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen, Fujian, China | 4Department of Psychiatry, Clinical Research Center for Depressive Disorder in Hunan Province, The Second People's Hospital of Hunan Province (Brain Hospital of Hunan Province), Changsha, China | 5Department of Radiology, The Second Xiangya Hospital of Central South University, Clinical Research Center for Medical Imaging in Hunan Province, Scientific Research Program of Hunan Provincial Health Commission, Changsha, Hunan, China | 6The Third People's Hospital of Tongren, Tongren, Guizhou, China Correspondence: Haishan Wu ([wuhaishan@csu.edu.cn](wuhaishan@csu.edu.cn)) Received: 12 September 2025 | Revised: 2 December 2025 | Accepted: 12 December 2025 Keywords: connectome-based predictive modeling | degree centrality | regional homogeneity | repeatable battery for the assessment of neuropsychological status | support vector machine ABSTRACT Background: This study aimed to identify neurobiomarkers that predict the efficacy of treatment of cognition in patients with bipolar disorder (BD) . Methods: Regional homogeneity (ReHo) and degree centrality (DC) values, which are two functional magnetic resonance imaging indicators, were analyzed to compare differences in brain activities between patients with BD and healthy controls (HC) . Results: BD patients (N = 92) exhibited increased activity in the right hippocampus or right parahippocampal gyrus compared to HC, while their ReHo and DC values in the left middle frontal gyrus decreased in the resting state. The delayed memory scores were predicted by using connectome-based predictive modeling in patients with BD at baseline. After 12 weeks of treatment, the patients with BD, whose cognitive function improved (n = 24), showed activity in the right superior temporal gyrus (STG) and left anterior cingulate cortex (ACC) at baseline. The improvement in cognitive function of patients with BD is distinguished by abnormal activities using support vector machine analysis. Conclusions: The abnormal frontal-limbic network plays a critical role in the underlying neuropathological mechanism of cognitive impairment in patients with BD. The right STG and left ACC hold the potential to serve as neurobiomarkers for predicting the clinical efficacy of cognitive function treatment. These regions provide additional target options for future physical treatments of cognitive impairment in patients with BD. | Sujuan Li and Yangpan Ou have contributed equally to this work and share co-first authorship. | | --- | | This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
© 2026 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd. | CNS Neuroscience & Therapeutics, 2026; 32:e70730 1 of 14 [https://doi.org/10.1002/cns.70730](https://doi.org/10.1002/cns.70730) 1 | Introduction Bipolar disorder (BD), also known as a chronic affective disorder, is characterized by recurrent episodes of depression and mania. The underlying mechanisms are not yet fully understood, and curren

FAQs

What is the main aim of this study?

To identify neurobiomarkers that predict how effective cognitive function treatment is for patients with bipolar disorder.

Which neuroimaging measures are analyzed?

The study analyzes regional homogeneity (ReHo) and degree centrality (DC) using functional MRI indicators.

What brain regions relate to cognitive improvement after treatment?

Patients whose cognitive function improved showed baseline activity changes involving the right superior temporal gyrus and the left anterior cingulate cortex, and abnormal frontal-limbic network activity was emphasized as key.

Sep 29, 2026

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