Differential effects of high-dose magnetic seizure therapy and electroconvulsive shock on cognitive function

Abstract

Background: Magnetic seizure therapy (MST) is under investigation as an alternative form of convulsive therapy that induces more focal seizures and spares cortical regions involved in memory. With a newly expanded version of the Columbia University Primate Cognitive Profile, we compared the cognitive effects of high-dose MST delivered at 100 Hz (6 x seizure threshold) with electroconvulsive shock (ECS) delivered at 2.5 x seizure threshold.

Methods: Daily high-dose MST, ECS, and sham (anesthesia-only) were administered for 4 weeks each in a within-subject crossover design. Rhesus macaques (n = 3) were trained on five cognitive tasks assessing automatic memory, anterograde learning and memory, combined anterograde and retrograde simultaneous chaining, and spatial and serial working memory. Acutely after each intervention, monkeys were tested on the cognitive battery twice daily, separated by a 3-hour retention interval.

Results: Subjects were slower to complete criterion tasks (p values < .0001) after ECS, compared with sham and high-dose MST. Moreover, time to task-completion after high-dose MST did not differ from sham. Of six measures of accuracy, treatment effects were found in four; in all of these, ECS but not MST fared worse than sham. On all accuracy and time to completion measurements, subjects performed as well after high-dose MST as subjects from a previous study on moderate-dose MST.

Conclusions: These findings provide evidence that high-dose MST results in benign acute cognitive side-effect profile relative to ECS and are in line with our previous studies.

Figure 1

Task 1: Recall of an over-learned stimulus. The subject must correctly select which among a field of 16 stimuli is the target. The target remains the same on every trial of every day, while the distracters and their screen positions change randomly between trials and days. A food pellet is given for each correct trial. Trials are presented until the subject gets 4 out of 5 consecutive trials correct.

Figure 2

Task 2: New target learning. The subject must learn, by selecting stimuli through trial and error, which stimulus among a field of 8 distracters is the target, then correctly select the target on 4 of 5 consecutive trials. Distracters change between trials and days. The target stimulus remains the same between trials on a given day, but it changes between days.

Figure 3

Task 3: Sequence learning and recall. The subject must learn, by trial and error, the correct sequence in which to select 3 simultaneously-presented. This task consisted of new lists, with a novel list presented each day on treatment days, and old lists, learned between 1 and 3 years previously.

Figure 4

Task 4: Spatial working memory task. 4, 5, or 6 identical stimuli are presented on the screen simultaneously. The subject must select each stimulus in turn without repeating a selection. Because the stimuli are identical and remain on the screen until the trial is over, they can be differentiated only by their respective locations on the screen. Between selections on a given trial, the subject must return to the center and select a “reset” stimulus.

Figure 5

Task 5: Serial Probe Recognition. A list of 4, 5, or 6 stimuli is presented one by one, with no delay between stimuli. The last stimulus in a given trial is followed by a 2 second delay. A “probe” stimulus is then presented, and the subject must select either a “yes” or “no” stimulus to indicate whether the probe had been in the list.

Figure 6

Task 3: Sequence memory. For previously learned (old) lists, ECS resulted in significantly poorer performance than in Baseline, MST, or Sham (* p ≤0.02). For new lists, ECS and MST did not differ from sham.

Figure 7

In Task 4, the spatial working memory task, ECS resulted in significantly lower scores than Sham (* p=0.0140). In Task 5, the serial probe recognition task, ECS resulted in lower scores than MST or Sham (* p<0.05).