Reciprocal relationships between stimulus duration, electroencephalography features, and cortical spreading depression during electroconvulsive therapy

Abstract

Abstract Electroconvulsive therapy (ECT) is effective for treating depression. Recent studies suggest that ECT can induce cortical spreading depression (CSD), which may have clinical benefits. However, the probability of CSD induction and its influence on therapeutically relevant real-time electroencephalography (EEG) features remain unknown. We investigated how electrical stimulus duration affects CSD induction probability and evaluated its reciprocal relationship with EEG features. In our study, EEG and direct-current potentials were recorded in 40 rats receiving transcranial-electrical stimulation for variable durations between 1-10 s. Seizure induction probabilities after transcranial-electrical stimulation were 75% for 1 s duration and 100% for longer durations. CSD induction probabilities detected by direct-current electrodes after transcranial-electrical stimulation were 13% (1 s), 100% (2 s), 88% (2.5 s), 75% (5 s), and 63% (10 s), respectively. High amplitude seizures were more likely to induce CSD (21.4 ± 5.3 µV vs 16.5 ± 5.0 µV, P = 0.0085), while CSD abruptly terminated seizure activities and showed longer postictal EEG suppression (205 ± 25 s vs 81 ± 57 s, P < 0.001). These results suggest that CSD induction has an optimal stimulus duration, and its induction probability tapers with increasing stimulus duration despite seizure induction. Furthermore, these findings indicate that ECT-induced CSD in our rodent model was associated with EEG features resembling those reported in favorable clinical responses to ECT.