groups in terms of their median saccade latencies (Figure 2A). However, average frequency distribution histograms (Figure 1) demonstrated an alteration of the relative proportions of saccades within latency ranges falling close to those suggested previously for express, fast and slow regular saccades [24]. The ESMs exhibited both a selective overproduction of express saccades, and a compli- mentary underproduction of saccades of longer latency. The distributions also confirmed that a latency range of 80 ms to 130 ms captured the ‘‘express peak’’ previously encountered infrequently in healthy na¨ıve participants in prosaccade overlap tasks [24,26]. In addition, the non-overlapping 95% confidence intervals suggest that the criterion we have used produces a clear separation of the two groups. The normal group exhibited saccade distributions essentially indistinguishable from those reported in many other studies. Our second objective was to compare ESM and normal participants, defined on the basis of their performance in the prosaccade task, using the antisaccade task [23,27]. Antisaccades require the inhibition of responses towards a suddenly appearing target (an error prosaccade), the transformation of the stimulus position into a voluntary motor command, and the execution of a voluntary saccade (the correct antisaccade) to the mirror image position of the stimulus. Antisaccade directional error rate was higher in the ESMs (41624%) compared to the normal subjects (28616%). While the distribution of correct antisaccade latency for ESM and normal groups was identical, a large express peak persisted in the ESM error prosaccade latency distribution. We also observed, that in the ESMs there was a slight asymmetry in the directional error rate; the rate tended to be higher when the target appeared to the right of fixation. This may be related to the production of ES, for which there is also a slight asymmetry, with more ES generated with targets on the right. Figure 5. Mean695%CI distributions for 60 normal subjects (A,B) and 16 ESMs (C,D) for correct antisaccades (A,C) and error prosaccades (B,D). The grey region shows the express saccade latency range (80 ms to 130 ms). The intersubject mean of the individual subject median latencies (6SD), and the intersubject percentage of express saccades is also shown. doi:10.1371/journal.pone.0047688.g005 ESM Antisaccade Performance Directional error rates vary between studies, and are affected by diverse methodological issues such as prior participant experience, task instructions, target eccentricity and number [27,28]. We used consistent methods and instructions across all participants and counterbalanced the order of overlap and antisaccade runs. We were explicit about instructing participants not simply to look in the opposite direction to the target, but to look to the mirror image position of the target. A synchronous antisaccade task was used (the saccade target appeared when the fixation target was extinguished) as opposed to a gap antisaccade task which encourages both the production of lower latency responses and express saccade errors [29]. An error rate of 23617% for a synchronous task (albeit with targets appearing at a range of eccentricities from 2u to 10u) for a large sample of over 2000 young men aged between 18 y and 24 y has been reported previously [30]. This compares reasonably well with the error rate in our normal participants (28616%). Given the variability in directional error rate in this and in many other studies, how should we interpret the difference we observed? A complementary approach is to calculate the difference as an ‘‘effect size’’. Often this is the effect size of an intervention (eg the comparison of some measurement in a treated group versus the same measurement in an untreated group). Here we compared the directional error rate in the ESM and normal groups using Cohen’s d [31,32]. The computed ‘‘effect size’’ (ie the standardised magnitude of the difference in error rate) was 0.69; this is considered to be a medium to large effect size [31,32]. Evdokimidis et al [30] plotted pooled latency distributions for both correct antisaccades and error prosaccades for their large sample. For correct antisaccades they showed a broad unimodal distribution with a mean (6SD) of 270639 ms, similar to what we observed in both ESM (290637 ms ) and normal groups (290661 ms; Figure 5A,C). Their distribution of error prosaccades was also unimodal (mean 208638 ms) with no responses at a latency of less than 120 ms. This is broadly similar to what we observed in normal participants (with regard to both the mean and variability; Figure 5B), but very different to the ESMs, where we observed both a large peak in the express range and a reduction in the proportion of saccades with longer latencies (Figure 5D). The second peak in the ESM distribution is at 160 ms, precisely where the main peak is in the distribution for the normal participants. While in the normal participant distribution there were some errors in the express range (11611%), the proportion was much smaller than in the ESMs (36626%). It is the generation of this population of express saccades that produces the overall statisti- cally significant reduction in error prosaccade latency in the ESMs, not a generalised shift of a unimodal distribution to the left. Thus, in circumstances where participants would be expected to inhibit reflexive responses, and in which they are aided by the use of a synchronous task rather than a gap task, ESMs continue to exhibit high proportions of express saccades. There were a number of relationships between parameters in the prosaccade and antisaccade tasks. Participants with lower median prosaccade saccade latency tended to be those with higher antisaccade directional error rates (Figure 6A) and lower antisaccade error prosaccade latency (Figure 6C). However, as discussed above, the ESMs exhibit a selective overproduction of saccades within a particular latency range, not a general reduction in saccade latency. Therefore median latency in the prosaccade task poorly captures the difference between groups, with consider- able overlap between normal and ESM participants. Not surprisingly when the data are plotted using the percentage of express saccades in prosaccade tasks, a clearer pattern emerges (Figure 6B,D). In common with other studies in which these PLOS ONE | www.plosone.org 5 October 2012 | Volume 7 | Issue 10 | e47688