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

Electroconvulsive therapy (ECT) is a well-established and effective treatment for severe depression and other conditions. Yet, it is unclear why seizures are therapeutic in ECT. This study used pre-treatment brain morphology to understand why some patients need less stimulation during ECT, as well as seizure length. Pre-existing MRI data were analyzed from four cohorts with treatment refractory depression undergoing right unilateral ECT (n = 166). Pretreatment regional brain morphometry and electrical current magnitude (|E|) were analyzed, along with seizure duration and stimulation charge at seizure threshold and 6x seizure threshold. Linear models controlled for age, sex, and cohort, corrected using false discovery rate q < 0.05. Charge at seizure threshold correlated with cortical surface area perpendicular to current flow and |E| in nearby white matter, perhaps suggesting cortical involvement during seizure titration. Stimulation charge during early supra-threshold treatments correlated with cortical morphology near the right temple electrode, |E| in right amygdala and anterior hippocampus, and volume in right mid-hippocampus and thalamus. Notably, antidepressant response correlated with cortical surface area near the temple electrode and |E| in right amygdala and anterior hippocampus, the latter of which mediated the effects of the former on antidepressant response. This suggests the importance of electrical stimulation in right anteromedial temporal lobe during therapeutic seizures in ECT. Cortical surface area extending between electrodes also positively correlated with seizure duration during early treatments. Taken together, these results suggest that pre-treatment brain morphology influences ECT-induced seizure. Personalized dosing based on head morphology and other factors may improve antidepressant outcomes and reduce side effects.