Brain morphometry, stimulation charge, and seizure duration in electroconvulsive therapy

Background Electroconvulsive therapy (ECT) is a well-established and effective treatment for severe depression and other conditions. Though ECT induces a generalized seizure, it is unclear why seizures are therapeutic. This study analyzed relationships between pre-treatment brain morphology, stimulation dose, and seizure duration to better understand ECT-induced seizures.

Pre-existing MRI data were analyzed from four cohorts with treatment refractory depression undergoing right unilateral (RUL) ECT (n=166). Regional brain morphometry and magnitude of electrical current (|E|) were analyzed, along with seizure duration and stimulation charge at seizure threshold (ECT1) and 6x seizure threshold (ECT2&3). Linear models controlled for age, sex, and cohort, corrected using false discovery rate q<0.05.

Lower ECT1 stimulation charge correlated with less cortical surface area perpendicular to current flow, and greater |E| in nearby white matter. Lower ECT2&3 stimulation charge correlated with less cortical surface area and curvature near the temporal electrode, higher |E| in right amygdala and anterior hippocampus, and lower right thalamic and mid-hippocampal volume. Cortical surface area extending between electrodes (e.g., postcentral gyrus) positively correlated with ECT2&3 seizure duration. Successful antidepressant response associated with less cortical surface area near the temporal electrode and more |E| in anteromedial temporal lobe regions, the latter of which mediated the effects of the former on antidepressant response.

Pre-treatment brain morphology influences ECT-induced seizure, particularly in regions near ECT electrodes and those relevant to seizure initiation and modulation. Personalized dosing based on head morphology and other factors may improve antidepressant outcomes and reduce side effects. Competing Interest Statement The authors have declared no competing interest. Funding Statement This work was supported by the NIH, including R03 MH121769 to Dr. Leaver, R01 MH092301 and U01 MH110008 to Drs. Narr and Espinoza, P20 GM103472 and U01 MH111826 to Dr. Abbott. This content is solely the responsibility of the authors and does not necessarily reflect the official views of the National Institutes of Health. This work was also supported in part through the computational resources and staff contributions provided for the Quest high performance computing facility at Northwestern University which is jointly supported by the Office of the Provost, the Office for Research, and Northwestern University Information Technology. This work was also supported in part by the Muriel Harris Chair of Geriatric Psychiatry at UCLA to Dr. Espinoza. 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: Northwestern University Institutional Review Board has approved a waiver for this research, stating that the research is exempt from review under category 4 (secondary research on data or specimens). 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 Data Availability The majority of this data are available at the NIMH Data Archive. All reasonable requests for other data not available in the NDA will be considered on a case-by-case basis by the individual authors responsible for each dataset (due to the sensitivity of the data).