Effects of pulse amplitude, pulse frequency, and stimulus duration on seizure threshold: A laboratory investigation

Background: Stimulus intensity during electroconvulsive therapy (ECT) is reckoned in units of charge (mC). The values of pulse amplitude, pulse width, pulse frequency, and stimulus duration can be varied to yield different composite stimuli, all of which have the same charge. There is little information on the extent to which variations in these stimulus parameters influence the seizure threshold at constant charge in the context of ECT. Methods: We administered once daily electroconvulsive shocks (ECS) to two groups of rats, starting with a stimulus intensity of 1 mC and increasing in 1 mC steps until the thresholds of each of three different types of seizure were identified. In one group (n = 10), the charge was raised first by increasing pulse amplitude and later by increasing pulse frequency. In the other group (n = 10), the charge was raised by increasing the stimulus duration only. Results: The mean seizure threshold ranged from 8.4 to 11.4 mC, depending on the type of seizure described, in the group in which pulse amplitude and frequency were manipulated; this range was 2.5 to 5.5 mC in the group in which the stimulus duration was manipulated (p < 0.001 for each of three types of seizures). Rats (n = 7) that did not convulse with an 8-mC stimulus in the amplitude and frequency group all convulsed with a 5-mC stimulus from the stimulus duration schedule. The first manifestation of seizure activity was significantly less likely to be generalized with amplitude and frequency titration than with stimulus duration titration (20% vs. 90%, respectively). The mean motor seizure durations (at different thresholds) were comparable with the two methods of stimulus titration. Conclusions: Seizure thresholds are lower when stimulus duration is the parameter that is increased during dose titration. The many clinical implications of this finding require study.