¹National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Bethesda, Maryland, United States

Background: Electroconvulsive therapy (ECT) remains the most effective treatment for severe, treatment-resistant depression, yet its clinical adoption is constrained by cognitive side effects stemming from widespread, non-specific E-field distribution across the brain. Present practice relies on standardized electrode placements, such as right unilateral or bitemporal, at fixed high current amplitudes, with no accommodation for individual neuroanatomy. Magnetic seizure therapy (MST) offers improved focality by confining seizure initiation to superficial cortex, with promising cognitive tolerability. Nevertheless, both ECT and MST lack the waveform flexibility and individualized targeting infrastructure needed to systematically optimize the efficacy–side-effect trade-off across patients.

Aims & Objectives: This talk presents the scientific rationale and engineering design principles underlying two next-generation seizure therapy devices. Objectives are to: (1) review the cognitive and efficacy evidence motivating innovation beyond conventional ECT and MST; (2) describe the design rationale and waveform features of the PROTECT (PRecision Optimally Targeted ECT) system; and (3) present the architecture, capabilities, and bench validation of the MIST (Multichannel Individualized Stimulation Therapy) device, which enables personalized multifocal stimulation through computational E-field modeling and optimization.

Method: Finite element method (FEM) simulations of E-field distributions were developed for conventional ECT montages (bitemporal, bifrontal, right unilateral), lateralized montages (FEAST, lateralized HD-ECT), 4×1-ring HD-ECT configurations, and an anatomically optimized multipolar HD-ECT montage across cortical and subcortical regions of interest. Peak E-field magnitudes were quantified at putative therapeutic targets (subgenual cingulate, nucleus accumbens) and cognitive antitargets (hippocampus, amygdala). The MIST device was developed as a 16-electrode, 15-channel programmable platform using H-bridge biphasic pulse topology, with independent current monitoring, impedance measurement, and integrated EEG/ECG/EMG acquisition to support individualized, computationally guided stimulation.

Results: Computational modeling demonstrated that conventional ECT montages produce diffuse E-fields reaching the hippocampus at 66%–139% of peak cortical E-field, with bitemporal stimulation generating the highest subcortical exposure. In contrast, a unilateral 4×1-ring HD-ECT configuration reduced hippocampal E-field to just 12% of peak cortex. A 9-electrode anatomically optimized multipolar montage achieved simultaneous targeting of the subgenual cingulate, hippocampus, and amygdala with substantially improved spatial specificity relative to conventional placements. MIST bench validation confirmed stimulus delivery across the full parameter space (up to 900 mA, 1.5 ms pulse width, 120 Hz, 8 s trains) with superior pulse edge precision and current amplitude stability compared to existing ECT devices.

Discussion & Conclusions: PROTECT and MIST represent complementary engineering responses to the core limitations of conventional ECT: waveform rigidity and anatomical nonspecificity. MIST, in particular, constitutes the first multichannel stimulation device for seizure therapy, combining flexible dosing, computational targeting, and comprehensive physiological monitoring in a single platform. Together with the spatial focality of MST, these devices chart a translational path toward seizure therapy that is more precise, more personalized, and better tolerated. Systematic preclinical validation and first-in-human studies will determine whether these computational and hardware advances translate into improved clinical outcomes for patients with severe psychiatric illness.