Analyzing Fractal Dimension in Electroconvulsive Therapy: Unraveling Complexity in Structural and Functional Neuroimaging

Background: Numerous studies show that electroconvulsive therapy (ECT) induces hippocampal neuroplasticity, but findings are inconsistent regarding its clinical relevance. This study aims to investigate ECT-induced plasticity of anterior and posterior hippocampi using mathematical complexity measures in neuroimaging, namely Higuchi's fractal dimension (HFD) for fMRI time series and the fractal dimension of cortical morphology (FD-CM). Furthermore, we explore the potential of these complexity measures to predict ECT treatment response. Methods: Twenty patients with a current depressive episode (16 with major depressive dis-order and 4 with bipolar disorder) underwent MRI-scans before and after an ECT-series. Twenty healthy controls matched for age and sex were also scanned twice for comparison purposes. Resting-state fMRI data were processed, and HFD was computed for anterior and posterior hippocampi. Group-by-time effects for HFD in anterior and posterior hippocampi were calculated and correlations between HFD changes and improvement in depression severity were examined. For baseline FD-CM analyses, we preprocessed structural MRI with CAT12's surface-based methods. We explored the predictive value of baseline HFD and FD-CM for treatment outcome. Results: Patients exhibited a significant increase in bilateral hippocampal HFD from baseline to follow-up scans. Right anterior hippocampal HFD increase was associated with reductions in depression severity. After applying a whole-brain regression analysis, we found that baseline FD-CM in the left temporal pole predicted reduction of overall depression se-verity after ECT. Baseline hippocampal HFD did not predict treatment outcome. Conclusion: This pioneering study suggests that HFD and FD-CM are promising imaging markers to investigate ECT-induced neuroplasticity associated with treatment response. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study received funding from the Robert Enke Foundation and the Novartis Foundation for medical biological research (to Tobias Bracht and Sebastian Walther) and the Swiss Life Foundation (to Tobias Bracht). Niklaus Denier and Tobias Bracht were both funded independently by a grant from the Adrian et Simone Frutiger Foundation. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All subjects provided written informed consent, and the study was approved by the local cantonal ethics committee of Bern, Switzerland (KEK-number: 2017-00731). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors