Focal electrically administered seizure therapy: a novel form of ECT illustrates the roles of current directionality, polarity, and electrode configuration in seizure induction

Abstract

Electroconvulsive therapy (ECT) is a mainstay in the treatment of severe, medication-resistant depression. The antidepressant efficacy and cognitive side effects of ECT are influenced by the position of the electrodes on the head and by the degree to which the electrical stimulus exceeds the threshold for seizure induction. However, surprisingly little is known about the effects of other key electrical parameters such as current directionality, polarity, and electrode configuration. Understanding these relationships may inform the optimization of therapeutic interventions to improve their risk/benefit ratio. To elucidate these relationships, we evaluated a novel form of ECT (focal electrically administered seizure therapy, FEAST) that combines unidirectional stimulation, control of polarity, and an asymmetrical electrode configuration, and contrasted it with conventional ECT in a nonhuman primate model. Rhesus monkeys had their seizure thresholds determined on separate days with ECT conditions that crossed the factors of current directionality (unidirectional or bidirectional), electrode configuration (standard bilateral or FEAST (small anterior and large posterior electrode)), and polarity (assignment of anode and cathode in unidirectional stimulation). Ictal expression and post-ictal suppression were quantified through scalp EEG. Findings were replicated and extended in a second experiment with the same subjects. Seizures were induced in each of the 75 trials, including 42 FEAST procedures. Seizure thresholds were lower with unidirectional than with bidirectional stimulation (p<0.0001), and lower in FEAST than in bilateral ECS (p=0.0294). Ictal power was greatest in posterior-anode unidirectional FEAST, and post-ictal suppression was strongest in anterior-anode FEAST (p=0.0008 and p=0.0024, respectively). EEG power was higher in the stimulated hemisphere in posterior-anode FEAST (p=0.0246), consistent with the anode being the site of strongest activation. These findings suggest that current directionality, polarity, and electrode configuration influence the efficiency of seizure induction with ECT. Unidirectional stimulation and novel electrode configurations such as FEAST are two approaches to lowering seizure threshold. Furthermore, the impact of FEAST on ictal and post-ictal expression appeared to be polarity dependent. Future studies may examine whether these differences in seizure threshold and expression have clinical significance for patients receiving ECT.

Figures

Figure 1

Study Design. This figure illustrates the conditions tested. Current directionality (shown in the columns) was either unidirectional or bidirectional. Electrode configuration (depicted in the rows) was either standard bilateral (BL) or Focal Electrically Applied Seizure Therapy (FEAST) with asymmetrically shaped electrodes. In Bidirectional conditions (far right column) each electrode serves as both anode and cathode for alternating pulses. In Unidirectional conditions (middle and left columns), one electrode serves as the anode (red) and one serves as the cathode (green). The small anterior anode unidirectional FEAST condition (bottom left, *) was added in Study 2. The other conditions were preformed in both Study 1 and Study 2. Each condition was replicated 4 times in each of 2 subjects, for a total of 8 replications per condition per study (total of 16 replications per condition across studies).

Figure 2

Seizure threshold as a function of electrode configuration and current directionality. Unidirectional had lower thresholds than bidirectional stimulation (*p

Figure 3

Ictal EEG power (log10(µV2)) by condition and frequency band. A: Combined data from Studies 1 and 2. FEAST had higher ictal power than BL, in the slower frequency bands (*p’s

Figure 4

Representative EEG tracing illustrating higher ictal power on the left hemisphere with posterior anode unidirectional FEAST.