Magnetic seizure therapy and electroconvulsive therapy increase frontal aperiodic activity

Major depressive disorder (MDD) is a leading cause of disability worldwide. One of the most efficacious treatments for treatment-resistant MDD is electroconvulsive therapy (ECT). Recently, magnetic seizure therapy (MST) was developed as an alternative to ECT due to its more favorable side effect profile. While these approaches have been very successful clinically, the neural mechanisms underlying their therapeutic effects are unknown. For example, clinical “slowing” of the electroencephalogram has been observed in both treatment modalities. A recent longitudinal study of a small cohort of ECT patients revealed that observed clinical slowing was better explained by increases in frontal aperiodic activity, an emerging EEG signal linked to neural inhibition. Here we investigate the role of aperiodic activity in a cohort of patients who received ECT and a cohort of patients who received MST treatment. We find that across treatments, frontal aperiodic activity better explains increases in delta band power associated with clinical slowing, compared to delta oscillations. Increased aperiodic activity is also linked to therapeutic efficacy, which is suggestive of a potential shared neural mechanism of action across ECT and MST: an increase in frontal inhibitory activity. ### Competing Interest Statement ATH was supported by an Alfred Deakin Postdoctoral Research Fellowship. DMB receives research support from the Canadian Institutes of Health Research (CIHR), National Institutes of Health - US (NIH), Brain Canada Foundation and the Temerty Family through the CAMH Foundation and the Campbell Family Research Institute. He received research support and in-kind equipment support for an investigator-initiated study from Brainsway Ltd. and he was the site principal investigator for three sponsor-initiated studies for Brainsway Ltd. He received in-kind equipment support from Magventure for investigator-initiated studies. He received medication supplies for an investigator-initiated trial from Indivior. He has participated in an advisory board for Janssen. He has participated in an advisory board for Welcony Inc. ZJD has received research and equipment in-kind support for an investigator-initiated study through Brainsway Inc and Magventure Inc and industry-initiated trials through Magnus Inc. He also currently serves on the scientific advisory board for Brainsway Inc. His work has been supported by the National Institutes of Mental Health (NIMH), the Canadian Institutes of Health Research (CIHR), Brain Canada and the Temerty Family, Grant and Kreutzcamp Family Foundations. ### Funding Statement NIH National Institute of General Medical Sciences grant R01GM134363-01 (to B.V.) ### 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: Ethics Committee of the Center for Addiction and Mental Health gave ethical approval for the study in accordance with the declaration of Helsinki. 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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data presented in the study is not available at this time.