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. 2025 Feb 20;5(3):100471.
doi: 10.1016/j.bpsgos.2025.100471. eCollection 2025 May.

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

Angel V Peterchev  1   2   3   4 , Zhi-De Deng  5 , Christopher Sikes-Keilp  1   6 , Elyssa C Feuer  7 , Moacyr A Rosa  1   8 , Sarah H Lisanby  5
Affiliations

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

Angel V Peterchev et al. Biol Psychiatry Glob Open Sci. .

Abstract

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.

Keywords: Electroconvulsive therapy; Frequency; Magnetic seizure therapy; Seizure duration; Seizure threshold; Titration.

Plain language summary

Electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) are forms of noninvasive brain stimulation that act by generating a seizure and are effective in the treatment of depression. This study in nonhuman primates identified the stimulation frequency that minimizes the amount of electricity delivered to the brain to generate a seizure, which could potentially minimize adverse effects. While the study did not assess therapeutic efficacy or side effects, the results highlight the significance of stimulation frequency for seizure generation and suggest efficient strategies for clinical practice and future clinical trials that explore the impact of frequency on efficacy and side effects.

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Figures

Figure 1
Figure 1
Illustration of the stimulus delivery configurations in a representative nonhuman primate subject. (A) Right unilateral electrode electroconvulsive therapy configuration. (B) Circular-coil-on-vertex magnetic seizure therapy configuration. Adapted with permission from Lee et al. (32).
Figure 2
Figure 2
Seizure threshold (ST) and seizure duration for electroconvulsive therapy (ECT) (orange) and magnetic seizure therapy (MST) (blue) as a function of stimulus pulse train frequency (pulses per second [pps]). (A) ST expressed as the number of pulses needed to induce a seizure at each frequency (stimulus total charge and energy are directly proportional to the number of pulses). (B) Duration of the stimulus pulse train at ST (filled markers) and respective observed motor seizure duration (open markers). Markers and whiskers indicate the mean and SD of the animal averages. The average for each animal was computed across all titration sessions at each frequency. Asterisks (∗) mark levels significantly different (p < .01) from the respective minimum across frequencies. All axes are logarithmically spaced. Individual data points are shown in Figures S1–S3.
Figure 3
Figure 3
Average electroencephalography (EEG) spectral power of ictal (A, B) and postictal (C, D) period relative to baseline for electroconvulsive therapy (ECT) (left) and magnetic seizure therapy (MST) (right) for various stimulation frequencies. The bottom row within each subplot corresponds to global EEG power, and rows above it correspond to discrete EEG bands (delta through beta). Individual raw and normalized data points are shown in Figures S9–S12. pps, pulses per second.
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References

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