Amplitude-determined seizure-threshold, electric field modeling, and electroconvulsive therapy antidepressant and cognitive outcomes

Electroconvulsive therapy (ECT) pulse amplitude, which dictates the induced electric field (E-field) magnitude in the brain, is presently fixed at 800 or 900 milliamperes (mA) without clinical or scientific rationale. We have previously demonstrated that increased E-field strength improves ECT’s antidepressant effect but worsens cognitive outcomes. Amplitude-determined seizure titration may reduce the E-field variability relative to fixed amplitude ECT. In this investigation, we assessed the relationships among amplitude-determined seizure-threshold (ST_a), E-field magnitude, and clinical outcomes in older adults (age range 50 to 80 years) with depression. Subjects received brain imaging, depression assessment, and neuropsychological assessment pre-, mid-, and post-ECT. ST_a was determined during the first treatment with a Soterix Medical 4×1 High Definition ECT Multi-channel Stimulation Interface (Investigation Device Exemption: G200123). Subsequent treatments were completed with right unilateral electrode placement (RUL) and 800 mA. We calculated E_brain defined as the 90th percentile of E-field magnitude in the whole brain for RUL electrode placement. Twenty-nine subjects were included in the final analyses. E_brain per unit electrode current, E_brain/I, was associated with ST_a. ST_a was associated with antidepressant outcomes at the mid-ECT assessment and bitemporal electrode placement switch. E_brain/I was associated with changes in category fluency with a large effect size. The relationship between ST_a and E_brain/I extends work from preclinical models and provides a validation step for ECT E-field modeling. ECT with individualized amplitude based on E-field modeling or ST_a has the potential to enhance neuroscience-based ECT parameter selection and improve clinical outcomes.