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

• Type of Material: Article
• Authors: Zening Fu, Emory University; Christopher C Abbott, University of New Mexico; Jeremy Miller, University of New Mexico; Zhi-De Deng, National Institute of Mental Health, National Institutes of Health, Bethesda; Shawn M McClintock, UT Southwestern Medical Center; Mohammed SE Sendi, Emory University; Jing Sui, Emory University; Vince Calhoun, Emory University
• Language: English
• Date: 2023-02-06
• Publisher: SPRINGERNATURE
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2023
• License: Creative Commons Attribution-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41398-023-02312-w
• Title of Journal or Parent Work: TRANSLATIONAL PSYCHIATRY
• Volume: 13
• Issue: 1
• Start Page: 43
• End Page: 43
• Grant/Funding Information: This work was supported by National Institutes of Health (R01MH118695, R01EB020407, R01MH117107, U01MH111826, and R61MH125126), the National Science Foundation (2112455), the National Institute of Mental Health Intramural Research Program (ZIAMH002955), and the China Natural Science Foundation (82022035).
• Keywords: HIPPOCAMPAL; Life Sciences & Biomedicine; DEPRESSION; COGNITION; CEREBELLAR VOLUME; CONNECTIVITY; NEUROGENESIS; Psychiatry; DISORDERS; NETWORKS; INCREASE; Science & Technology; EMOTION
• Research Categories: Health Sciences, Mental Health; Psychology, Behavioral

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.