Ultra-highfield neuroimaging for the multimodal investigation of neuroplasticity related effects of electroconvulsive therapy (ECT)

• Applicants: Professor Dr. Dimo Ivanov; Professor Dr. Nils Opel; Professor Dr. Jonathan Repple; Professor Dr. Martin Walter
• Subject Area: Biological Psychiatry
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 571864092

Electroconvulsive therapy (ECT) is one of the most effective interventions for severe and treatment-resistant depression, yet its underlying mechanisms of action remain largely unexplored. Understanding these mechanisms is crucial for optimizing ECT protocols and improving patient outcomes. This study aims to investigate the neuroplasticity-related effects of(ECT on patients with major depressive disorder (MDD). Utilizing multimodal ultra-highfield neuroimaging, we will examine the relationship between short-term changes in neurotransmitter levels in several brain regions, specifically the anterior cingulate cortex (ACC) subregions and the delayed structural and functional brain network effects of ECT. We will focus on two main objectives: First, we will investigate the relationship between changes in neurotransmitter levels and subsequent alterations in brain network function and structure. Second, we will delineate the temporal and regional specificity of ECT effects on neural networks associated with dysfunctional emotional and cognitive processing in MDD. To this end, we will conduct a bicentric prospective naturalistic observational study at the University of Jena and the University of Frankfurt. The study will enroll 60 patients (30 per site) with severe depression undergoing ECT as part of their clinical routine. Participants will be assessed at three time points: before treatment (t0), after the first ECT session (t1), and after completing the ECT series (t2). MRI and comprehensive phenotyping will be conducted at each time point. We hypothesize that (1) ECT induces a short-term increase in excitatory neurotransmitter (glutamate) levels in the subgenual and pregenual ACC detectable after the first ECT session; (2) this increase in glutamate levels is associated with enhanced functional coupling between the ACC subregions and a depression-specific brain circuit (3) short-term glutamate increases and functional coupling are linked to delayed increases in gray matter volume and structural connectivity in these regions and (4) changes in neurotransmitter levels and brain network function in the ACC predict clinical outcomes following ECT. Additionally, we will investigate in additional exploratory analyses whether changes in ACC subdivisions relate differentially to affective and cognitive symptoms of depression, and whether pretreatment differences in ACC node integration within the depression network predicts brain network changes and clinical outcomes. This study will provide critical insights into the neurobiological mechanisms underlying the therapeutic effects of ECT in MDD. By leveraging the ultra-high resolution of 7T MRI, we aim to advance our understanding of how ECT modulates brain structure and function, potentially identifying biomarkers for treatment response and informing personalized therapeutic strategies.

• DFG Programme: Research Grants