Optimal Frequency for Seizure Induction With Electroconvulsive Therapy and Magnetic Seizure Therapy in Nonhuman Primates.

Background: Electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) are effective in the treatment of medication-resistant depression. Determining the stimulus frequency that results in the lowest seizure threshold could produce fewer adverse effects by reducing the overall stimulus intensity. Methods: To determine the optimal frequency for seizure induction, 4 male rhesus macaques were titrated with an increasing number of pulses at fixed frequencies ranging from 5 to 240 pulses per second (pps) using ultrabrief pulse right-unilateral ECT and circular-coil-on-vertex MST. Bilateral electroencephalography was recorded to characterize the seizure expression. Results: The seizure threshold dependence on stimulus frequency was similar for ECT and MST. While higher frequencies required progressively shorter trains to induce a seizure, the middle frequency range was associated with the fewest pulses (and therefore the least charge and energy), with a minimum at 16 pps and similarly low thresholds for 10 and 25 pps. The number of pulses at seizure threshold increased markedly at lower and higher frequencies. The lowest stimulus frequencies, 5 and 10 pps, were associated with the greatest ictal power measured by electroencephalography. Conclusions: While neither efficacy nor side effects were assessed in this study, the results highlight the significance of stimulus frequency for seizure induction, suggest efficient titration schedules that minimize exposure to the electrical stimulus, and can inform studies to assess the impact on clinical outcomes. These data can also support safety guidelines for interventions such as transcranial magnetic stimulation that must avoid seizure induction.