Thalamocortical white matter connectivity and the entorhinal cortex as neural correlates of electroconvulsive therapy response in patients with schizophrenia spectrum disorder

Background: Electroconvulsive therapy (ECT) is an effective treatment for patients with treatment-resistant schizophrenia spectrum disorder (SSD); however, the underlying mechanisms of ECT remain unclear, and region-specific neuromodulation targets are not well defined. Abnormally reduced thalamo-pr...

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Main Authors: Minah Kim, Eugenie Choe, Hyungyou Park, Silvia Kyungjin Lho, Sun-Young Moon, Sanghoon Oh, Jun Soo Kwon
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Brain Stimulation
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Online Access:http://www.sciencedirect.com/science/article/pii/S1935861X25002591
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author Minah Kim
Eugenie Choe
Hyungyou Park
Silvia Kyungjin Lho
Sun-Young Moon
Sanghoon Oh
Jun Soo Kwon
author_facet Minah Kim
Eugenie Choe
Hyungyou Park
Silvia Kyungjin Lho
Sun-Young Moon
Sanghoon Oh
Jun Soo Kwon
author_sort Minah Kim
collection DOAJ
description Background: Electroconvulsive therapy (ECT) is an effective treatment for patients with treatment-resistant schizophrenia spectrum disorder (SSD); however, the underlying mechanisms of ECT remain unclear, and region-specific neuromodulation targets are not well defined. Abnormally reduced thalamo-prefrontal cortex (PFC) and increased thalamo-parietal cortex (PC) connectivity have been linked to schizophrenia pathophysiology. In this study, thalamocortical white matter (WM) connectivity was examined as a potential biomarker of ECT response, and the brain regions that mediate ECT-induced changes in SSD patients were explored. Methods: Twenty-six SSD patients and 28 age- and sex-matched healthy controls (HCs) underwent diffusion-weighted magnetic resonance imaging to assess thalamocortical WM connectivity. SSD patients were scanned twice, before (T1) and after (T2) ECT, over 1–2 months. Associations between changes in thalamocortical WM connectivity and symptom improvement were analyzed. Mediation analysis using graph theoretical analysis of structural connectomes was performed to identify modulating regions associated with WM connectivity changes. Results: At T1, SSD patients exhibited lower thalamo-lateral PFC and greater thalamo-PC WM connectivity than HCs did. At T2, the group-level difference in thalamo-PC WM connectivity disappeared. In SSD patients, thalamo-PC WM connectivity significantly decreased between T1 and T2, which was associated with symptom improvement. Mediation analysis revealed that the degree centrality of the right entorhinal cortex significantly mediated ECT-induced changes in thalamo-PC WM connectivity. Conclusion: These findings suggest that a reduction in increased thalamo-PC WM connectivity may be a biomarker for ECT response in SSD patients. Furthermore, the right entorhinal cortex may be a neuromodulation target for treatment-resistant SSD.
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spelling doaj-art-5d5632f1a5e945afb70b52a89a2ed3fe2025-08-20T02:57:04ZengElsevierBrain Stimulation1935-861X2025-07-011841190119610.1016/j.brs.2025.06.007Thalamocortical white matter connectivity and the entorhinal cortex as neural correlates of electroconvulsive therapy response in patients with schizophrenia spectrum disorderMinah Kim0Eugenie Choe1Hyungyou Park2Silvia Kyungjin Lho3Sun-Young Moon4Sanghoon Oh5Jun Soo Kwon6Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea; Institute of Human Behavioral Medicine, SNU-MRC, Seoul, Republic of KoreaDepartment of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea; Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine, Seoul, Republic of KoreaDepartment of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, Republic of KoreaDepartment of Psychiatry, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of KoreaDepartment of Public Health Medical Services, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of KoreaDepartment of Psychiatry, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu, Gyeonggi-do, Republic of KoreaInstitute of Human Behavioral Medicine, SNU-MRC, Seoul, Republic of Korea; Department of Psychiatry, Hanyang University Hospital, Seoul, Republic of Korea; Corresponding author. Department of Psychiatry, Hanyang University Hospital, 222-1 Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea.Background: Electroconvulsive therapy (ECT) is an effective treatment for patients with treatment-resistant schizophrenia spectrum disorder (SSD); however, the underlying mechanisms of ECT remain unclear, and region-specific neuromodulation targets are not well defined. Abnormally reduced thalamo-prefrontal cortex (PFC) and increased thalamo-parietal cortex (PC) connectivity have been linked to schizophrenia pathophysiology. In this study, thalamocortical white matter (WM) connectivity was examined as a potential biomarker of ECT response, and the brain regions that mediate ECT-induced changes in SSD patients were explored. Methods: Twenty-six SSD patients and 28 age- and sex-matched healthy controls (HCs) underwent diffusion-weighted magnetic resonance imaging to assess thalamocortical WM connectivity. SSD patients were scanned twice, before (T1) and after (T2) ECT, over 1–2 months. Associations between changes in thalamocortical WM connectivity and symptom improvement were analyzed. Mediation analysis using graph theoretical analysis of structural connectomes was performed to identify modulating regions associated with WM connectivity changes. Results: At T1, SSD patients exhibited lower thalamo-lateral PFC and greater thalamo-PC WM connectivity than HCs did. At T2, the group-level difference in thalamo-PC WM connectivity disappeared. In SSD patients, thalamo-PC WM connectivity significantly decreased between T1 and T2, which was associated with symptom improvement. Mediation analysis revealed that the degree centrality of the right entorhinal cortex significantly mediated ECT-induced changes in thalamo-PC WM connectivity. Conclusion: These findings suggest that a reduction in increased thalamo-PC WM connectivity may be a biomarker for ECT response in SSD patients. Furthermore, the right entorhinal cortex may be a neuromodulation target for treatment-resistant SSD.http://www.sciencedirect.com/science/article/pii/S1935861X25002591Electroconvulsive therapyDiffusion tensor imagingMediating regionThalamocortical connectivityTreatment responseSchizophrenia
spellingShingle Minah Kim
Eugenie Choe
Hyungyou Park
Silvia Kyungjin Lho
Sun-Young Moon
Sanghoon Oh
Jun Soo Kwon
Thalamocortical white matter connectivity and the entorhinal cortex as neural correlates of electroconvulsive therapy response in patients with schizophrenia spectrum disorder
Brain Stimulation
Electroconvulsive therapy
Diffusion tensor imaging
Mediating region
Thalamocortical connectivity
Treatment response
Schizophrenia
title Thalamocortical white matter connectivity and the entorhinal cortex as neural correlates of electroconvulsive therapy response in patients with schizophrenia spectrum disorder
title_full Thalamocortical white matter connectivity and the entorhinal cortex as neural correlates of electroconvulsive therapy response in patients with schizophrenia spectrum disorder
title_fullStr Thalamocortical white matter connectivity and the entorhinal cortex as neural correlates of electroconvulsive therapy response in patients with schizophrenia spectrum disorder
title_full_unstemmed Thalamocortical white matter connectivity and the entorhinal cortex as neural correlates of electroconvulsive therapy response in patients with schizophrenia spectrum disorder
title_short Thalamocortical white matter connectivity and the entorhinal cortex as neural correlates of electroconvulsive therapy response in patients with schizophrenia spectrum disorder
title_sort thalamocortical white matter connectivity and the entorhinal cortex as neural correlates of electroconvulsive therapy response in patients with schizophrenia spectrum disorder
topic Electroconvulsive therapy
Diffusion tensor imaging
Mediating region
Thalamocortical connectivity
Treatment response
Schizophrenia
url http://www.sciencedirect.com/science/article/pii/S1935861X25002591
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