Electroconvulsive therapy (ECT) is the most effective treatment for depression, yet its working mechanism remains unclear. In the animal analog of ECT, neurogenesis in the dentate gyrus (DG) of the hippocampus is observed. In humans, volume increase of the hippocampus has been reported, but accurately measuring the volume of subfields is limited with common MRI protocols. If the volume increase of the hippocampus in humans is attributable to neurogenesis, it is expected to be exclusively present in the DG, whereas other processes (angiogenesis, synaptogenesis) also affect other subfields. Therefore, we acquired an optimized MRI scan at 7-tesla field strength allowing sensitive investigation of hippocampal subfields. A further increase in sensitivity of the within-subjects measurements is gained by automatic placement of the field of view. Patients receive two MRI scans: at baseline and after ten bilateral ECT sessions (corresponding to a 5-week interval). Matched controls are also scanned twice, with a similar 5-week interval. A total of 31 participants (23 patients, 8 controls) completed the study. A large and significant increase in DG volume was observed after ECT (M = 75.44 mm 3 , std error = 9.65, p < 0.001), while other hippocampal subfields were unaffected. We note that possible type II errors may be present due to the small sample size. In controls no changes in volume were found. Furthermore, an increase in DG volume was related to a decrease in depression scores, and baseline DG volume predicted clinical response. These findings suggest that the volume change of the DG is related to the antidepressant properties of ECT, and may reflect neurogenesis.

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Background: Volume increases of the hippocampus after electroconvulsive therapy (ECT) are a robust finding, pointing into the direction of neurogenesis. However, such volumetric increases could also be explained by edema and/or neuroplastic changes (such as angiogenesis). Objectives: If edema explains the volume increase of the hippocampus we hypothesize it would lead to increased mean diffusivity (MD). If neuroplastic would explain the volume increase, it would lead to decreased MD. To investigate angiogenesis as explanation we studied the perfusion fraction f and the pseudodiffusion component D* obtained from intravoxel incoherent motion (IVIM) data, and relative perfusion changes obtained from arterial spin labelling (ASL) data. Methods: Using ultra-high field (7 tesla) MRI we acquired IVIM and ASL data. We compared MD, f, D* and ASL values for both hippocampi in 21 patients (before and after 10 ECT sessions) and 8 healthy controls (without ECT) in a linear mixed model adjusting for age and gender. Results: We found a significant decrease in MD (which was absent in the healthy controls) in the left and right hippocampus (t ¼ -3.98, p < 0.001). In addition, a decrease in f (t ¼ -4.61, p < 0.001, but not in controls) and no differences in D* or ASL perfusion values (both p > 0.05) were found. Conclusions: The decrease in MD in perfusion fraction f suggest that formation of edema nor angiogenesis are responsible for the ECT-induced volume increases in the hippocampus. Also, it supports the hypothesis that hippocampal volume increases might be due to neuroplastic changes.