alteration in oculomotor processing, then their performance should be distinguishable from non-ESM participants across testing paradigms. And their performance in other task types should provide important additional information allowing stronger inferences to be made about which specific aspects of the saccade system (in both functional and anatomical terms) are altered in ESMs. Finally, if ESMs, defined on the basis of their performance on reflexive saccade tasks, do perform differently from non-ESM participants in other task types, this would add validity to their classification as a distinct group. We therefore tested a large group of na¨ıve Chinese participants in order to identify ESMs, and to confirm whether ESMs occurred in larger numbers than expected. We then used the antisaccade task [22,23], which requires the participant to inhibit a reflexive saccade towards a target, and compute and execute a voluntary saccade to the mirror image of the target position, to explore their oculomotor control further. Directional errors, composed of error prosaccades (saccades towards the target), reflect problems inhibiting reflexive responses. Correct antisaccade latency is considerably greater than the latency of error prosaccades, because of both the processing required to inhibit the reflexive response and to compute the appropriate voluntary saccade. Antisaccade task performance is critically dependent on a number of cortical areas, particularly the frontal eye fields (FEF) and dorsolateral prefrontal cortex (dlPFC) [23]. Materials and Methods Ethics Statement Experiments were specifically approved by the West China Hospital of the University of Sichuan Ethics Committee. All participants provided their written informed consent and experi- ments were performed in accordance with the ethical standards laid down in the Declaration of Helsinki (as modified 2004). Participants A total of 77 healthy, na¨ıve, adult participants with normal or corrected to normal visual acuity were recruited from staff and students of, and tested in, the West China Hospital, Chengdu, China. The median age of the group was 24 y (range 19 y–45 y), and 39 (50%) were male. All were Han Chinese. Apparatus and Stimuli Horizontal eye movements were recorded binocularly with the same miniaturized head-mounted infrared saccadometer (Ad- vanced Clinical Instrumentation, Cambridge, UK) used in our previous experiment [10]. This samples infrared reflectance signals at 1 KHz, and low-pass filters them at 250 Hz with 12-bit resolution. The device incorporates three low-power red lasers projecting 13 cd/m2 target spots subtending approximately 0.1u, in a horizontal line, centrally and at 10u to left and right of centre. As the stimuli move with the head, participants were not head- fixed; they sat in a comfortable position approximately 1.5 m in front of a near-white surface. We exposed participants to two blocks of trials of two types: prosaccade overlap and synchronous antisaccade trials. Each block consisted of two runs of 200 trials (thus we had a potential maximum of 400 trials of each type). In prosaccade trials after a randomised fixation time of 1 s–2 s, a saccade target appeared randomly 10u to the right or left of the central fixation target while the fixation target remained illuminated. Participants were instructed to saccade to the eccentric target as soon as they detected it. These tasks were identical to the prosaccade overlap tasks that we used previously [10]. In antisaccade trials a synchro- ESM Antisaccade Performance nous task was used in which after the same variable fixation time the fixation target was extinguished and a saccade target appeared randomly 10u to the right or left. Participants were instructed not to look at the target, but to saccade to its mirror image position ie 10u from the central fixation target, in the opposite direction to the target. At the beginning of each run we stepped through the task while giving verbal instructions. We asked participants to respond as quickly and accurately as they were able, and during the antisaccade runs provided verbal reminders to ‘‘look in the opposite direction from the target, but the same distance from fixation’’. The order of the two prosaccade and antisaccade blocks was counterbalanced across participants. Analysis Data were stored on the Saccadometer handset, and down- loaded for offline analysis using the supplied software (Latency Meter 4.0). The latency and amplitude of each prosaccade from the overlap blocks were collated and saccade latency distributions calculated for each individual participant. We excluded from the analysis saccades with a latency of less than 50 ms or more than 500 ms. Median latency and mean saccade amplitude were calculated for each participant. We also calculated the percentage of express saccades, that is those saccades with latency in the range 80 ms to 130 ms [14,24]. We defined participants who had greater than 30% of their saccades in this range as ‘‘express saccade makers’’ (ESMs [10,15]). For each participant we calculated antisaccade directional error rate (ie the number of saccades towards the target in antisaccade tasks, as a percentage of the total), median prosaccade error latency, and median antisaccade latency (for all saccades with latency between 50 ms and 700 ms). For each participant the distribution of these latencies was also calculated. We also calculated mean saccade amplitude for prosaccade errors and correct antisaccades. Results Prosaccade Tasks Prosaccade overlap data were obtained for all 77 participants. The intersubject mean median saccade latency across all 77 was 184632 ms. However, we observed a high number of individual frequency distributions histograms (Figure 1A,B) in which there was a clear early latency peak, centred close to 100 ms (Figure 1B; all the individual frequency distributions histograms are shown in Supporting Information as Figures S1 and S2). In 17 of the 77 participants (22%), the proportion of saccades with latency in the range 80 ms to 130 ms (express saccades, ES) exceeded 30% (Figure 2). We defined these 17 participants as ‘‘express saccade makers’’ (ESMs) and the remaining participants as ‘‘normal’’. Mean median latency and percentage of ES for the ESMs were 150622 ms and 43610% compared to 193628 ms and 1267% for the 60 normals respectively. Both latency (t = 5.67; p,0.0001) and percentage of express saccades (t = 13.37; p,0.0001) were statistically significantly different between these two groups. For each group, the individual percentage distribution histo- grams for each participant were used to calculate the mean (695% CI) percentage for each 10 ms histogram bin in order to construct a mean distribution histogram (Figure 1C,D). This analysis confirmed a group difference in latency distributions, with the most noticeable feature being the early peak in the ESM distribution centred at around 100 ms. However, this analysis also suggested that this early peak in the ESM distribution was complemented by later peaks at 160 ms and 210 ms where the percentages were greater in the normal compared to the ESM distribution. We compared the mean bin values across the ranges PLOS ONE | www.plosone.org 2 October 2012 | Volume 7 | Issue 10 | e47688