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Updated: Oct 1, 2026
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Microstructural changes in deep gray nuclei following electroconvulsive therapy
Christopher G Filippi1, Matthew Yh Leung2, Aziz M Ulug2
1From the Radiology (C.G.F.), Neuroscience and Mental Health (C.G.F.), The Hospital for Sick Children, Toronto, Canada; Neuroradiology (M.Y.H.L.), Department of Medical Imaging, University of Toronto, Toronto, Canada; School of Medicine (M.Y.H.L.), The University of Sydney, Sydney, Australia; Cortechs Labs (A.M.U.), San Diego, USA; Biyomedikal Mühendisliği Enstitüsü (A.M.U.), Boğaziçi University, Istanbul, Turkey; Ahmanson-Lovelace Brain Mapping Center, Department of Neurology (A.Z.-P.), Geffen School of Medicine at the University of California, Los Angeles, CA, USA and University of Canterbury (R.W.), Christchurch, New Zealand. risto.filippi@sickkids.ca.
Background And Purpose:
Electroconvulsive therapy (ECT) is efficacious for the treatment of major depressive disorder. However, its underlying mechanism of action remains debated and may involve neurogenesis, changes in axon/synaptic density or glial cells. Restriction spectrum imaging (RSI) is an MRI technique that can resolve subvoxel microstructure, separating intracellular water from extracellular water, which can be further partitioned into hindered and free water. This technique can be used to determine whether ECT affects cellular microstructure through changes in signal contributions. In the present study, we aim to determine how RSI metrics change following ECT and whether these metrics correlate with clinical improvement.
Methods:
RSI analysis of the Perturbation of Depression Connectome (PDC 1.0) diffusion MRI data for healthy control and predominantly right unilateral ECT patients. MRI studies were undertaken at baseline, 1-week post-treatment and 3-months post ECT (follow-up).
Results:
Following ECT, right-sided RSI metrics changed in cortical and subcortical brain regions including right amygdala and right hippocampus between baseline and post-treatment. The hindered water compartment increased, the free water compartment decreased, and the intracellular compartment was unchanged. Post-treatment, volume increased in the amygdala and hippocampus, which partially resolved at follow-up, while right amygdala extracellular indices persisted. Changes in clinical symptoms did not clearly relate to volumetric or diffusion changes.
Conclusions:
RSI provides imaging biomarkers that suggest extracellular water shifts with corresponding volume changes to be the predominant effect of ECT. Transient and longer-term changes in glymphatic flow may be one of the contributing, underlying mechanisms of action for ECT.
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