Cerebro-cerebellar functional neuroplasticity mediates the effect of electric field on electroconvulsive therapy outcomes

Abstract Electroconvulsive therapy (ECT) is the most effective treatment for severe depression and works by applying an electric current through the brain. The applied current generates an electric field (E-field) and seizure activity, changing the brain’s functional organization. The E-field, which...

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Main Authors: Zening Fu, Christopher C. Abbott, Jeremy Miller, Zhi-De Deng, Shawn M. McClintock, Mohammad S. E. Sendi, Jing Sui, Vince D. Calhoun
Format: Article
Language:English
Published: Nature Publishing Group 2023-02-01
Series:Translational Psychiatry
Online Access:https://doi.org/10.1038/s41398-023-02312-w
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author Zening Fu
Christopher C. Abbott
Jeremy Miller
Zhi-De Deng
Shawn M. McClintock
Mohammad S. E. Sendi
Jing Sui
Vince D. Calhoun
author_facet Zening Fu
Christopher C. Abbott
Jeremy Miller
Zhi-De Deng
Shawn M. McClintock
Mohammad S. E. Sendi
Jing Sui
Vince D. Calhoun
author_sort Zening Fu
collection DOAJ
description Abstract Electroconvulsive therapy (ECT) is the most effective treatment for severe depression and works by applying an electric current through the brain. The applied current generates an electric field (E-field) and seizure activity, changing the brain’s functional organization. The E-field, which is determined by electrode placement (right unilateral or bitemporal) and pulse amplitude (600, 700, or 800 milliamperes), is associated with the ECT response. However, the neural mechanisms underlying the relationship between E-field, functional brain changes, and clinical outcomes of ECT are not well understood. Here, we investigated the relationships between whole-brain E-field (Ebrain, the 90th percentile of E-field magnitude in the brain), cerebro-cerebellar functional network connectivity (FNC), and clinical outcomes (cognitive performance and depression severity). A fully automated independent component analysis framework determined the FNC between the cerebro-cerebellar networks. We found a linear relationship between Ebrain and cognitive outcomes. The mediation analysis showed that the cerebellum to middle occipital gyrus (MOG)/posterior cingulate cortex (PCC) FNC mediated the effects of Ebrain on cognitive performance. In addition, there is a mediation effect through the cerebellum to parietal lobule FNC between Ebrain and antidepressant outcomes. The pair-wise t-tests further demonstrated that a larger Ebrain was associated with increased FNC between cerebellum and MOG and decreased FNC between cerebellum and PCC, which were linked with decreased cognitive performance. This study implies that an optimal E-field balancing the antidepressant and cognitive outcomes should be considered in relation to cerebro-cerebellar functional neuroplasticity.
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spelling doaj.art-ffe56131d48341648fd93f4d32444b262023-02-12T12:23:27ZengNature Publishing GroupTranslational Psychiatry2158-31882023-02-0113111110.1038/s41398-023-02312-wCerebro-cerebellar functional neuroplasticity mediates the effect of electric field on electroconvulsive therapy outcomesZening Fu0Christopher C. Abbott1Jeremy Miller2Zhi-De Deng3Shawn M. McClintock4Mohammad S. E. Sendi5Jing Sui6Vince D. Calhoun7Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, Emory UniversityDepartment of Psychiatry, University of New MexicoDepartment of Psychiatry, University of New MexicoComputational Neurostimulation Research Program, Noninvasive Neuromodulation Unit, Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of HealthDivision of Psychology, Department of Psychiatry, UT Southwestern Medical CenterTri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, Emory UniversityTri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, Emory UniversityTri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, Emory UniversityAbstract Electroconvulsive therapy (ECT) is the most effective treatment for severe depression and works by applying an electric current through the brain. The applied current generates an electric field (E-field) and seizure activity, changing the brain’s functional organization. The E-field, which is determined by electrode placement (right unilateral or bitemporal) and pulse amplitude (600, 700, or 800 milliamperes), is associated with the ECT response. However, the neural mechanisms underlying the relationship between E-field, functional brain changes, and clinical outcomes of ECT are not well understood. Here, we investigated the relationships between whole-brain E-field (Ebrain, the 90th percentile of E-field magnitude in the brain), cerebro-cerebellar functional network connectivity (FNC), and clinical outcomes (cognitive performance and depression severity). A fully automated independent component analysis framework determined the FNC between the cerebro-cerebellar networks. We found a linear relationship between Ebrain and cognitive outcomes. The mediation analysis showed that the cerebellum to middle occipital gyrus (MOG)/posterior cingulate cortex (PCC) FNC mediated the effects of Ebrain on cognitive performance. In addition, there is a mediation effect through the cerebellum to parietal lobule FNC between Ebrain and antidepressant outcomes. The pair-wise t-tests further demonstrated that a larger Ebrain was associated with increased FNC between cerebellum and MOG and decreased FNC between cerebellum and PCC, which were linked with decreased cognitive performance. This study implies that an optimal E-field balancing the antidepressant and cognitive outcomes should be considered in relation to cerebro-cerebellar functional neuroplasticity.https://doi.org/10.1038/s41398-023-02312-w
spellingShingle Zening Fu
Christopher C. Abbott
Jeremy Miller
Zhi-De Deng
Shawn M. McClintock
Mohammad S. E. Sendi
Jing Sui
Vince D. Calhoun
Cerebro-cerebellar functional neuroplasticity mediates the effect of electric field on electroconvulsive therapy outcomes
Translational Psychiatry
title Cerebro-cerebellar functional neuroplasticity mediates the effect of electric field on electroconvulsive therapy outcomes
title_full Cerebro-cerebellar functional neuroplasticity mediates the effect of electric field on electroconvulsive therapy outcomes
title_fullStr Cerebro-cerebellar functional neuroplasticity mediates the effect of electric field on electroconvulsive therapy outcomes
title_full_unstemmed Cerebro-cerebellar functional neuroplasticity mediates the effect of electric field on electroconvulsive therapy outcomes
title_short Cerebro-cerebellar functional neuroplasticity mediates the effect of electric field on electroconvulsive therapy outcomes
title_sort cerebro cerebellar functional neuroplasticity mediates the effect of electric field on electroconvulsive therapy outcomes
url https://doi.org/10.1038/s41398-023-02312-w
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