This time-sensitivity could arise because the SEF’s functionality is only required in the immediate peri-saccadic interval, or because the SEF can recover from disruptive effects of ICMS delivered earlier in the fixation interval. The observed time-sensitivity follows a time-course similar to the evolution of SEF activity during an intermixed pro- and anti-saccade task (Amador et al., 2004), consistent with the functional relevance of this area for anti-saccade performance in the primate. To our knowledge, previous studies employing ICMS-SEF have not investigated the anti-saccade task, hindering direct comparison of our data with the literature. The effects we report of ICMS-SEF

on anti-saccade performance are particularly interesting in light of the report by Stuphorn & Schall (2006) that subthreshold ICMS-SEF improved performance in a stop-signal Obeticholic Acid solubility dmso task by delaying saccade generation. In their case, ICMS-SEF served an adaptive purpose when executive control was occasionally required: by delaying saccades, more time was provided for saccade cancellation. A different picture emerges from our data, where the increase in anti-saccade errors is accompanied by a marked bilateral

increase in the RTs of correct anti-saccades (Fig. 3). Although short-duration ICMS-SEF delayed anti-saccades, it did not confer any benefit to anti-saccade accuracy but instead also incurred a substantial cost. The differences between our results and those of Stuphorn & Schall (2006) could arise from the nature of the behavioral tasks and the Adriamycin in vitro state of the oculomotor system at the time of stimulation; in our task monkeys were prepared for an anti-saccade by the time ICMS-SEF exerted the largest effects, whereas saccade cancellation in the stop-signal task is required on a minority of trials. Alternatively (or perhaps additionally), the differences may arise from the parameters of subthreshold stimulation; we opted for shorter durations and higher currents (30 ms of 100 μA at 300 Hz), whereas Stuphorn

and see more Schall used longer durations and lower currents (200 ms of 10 μA or less at 333 Hz). What our results share in common with those of Stuphorn and Schall is the state-dependency; they noted that ICMS-SEF delayed saccades when delivered during a stop-signal task, but expedited visually guided saccades otherwise. In our case, the disruption of performance is greater for anti-saccades, with ICMS-SEF only weakly influencing pro-saccades. A greater influence of ICMS-SEF on more cognitively demanding tasks is also consistent with the results of Kunimatsu & Tanaka (2012), who showed greater delays from ICMS-SEF for self-initiated vs. conventional memory-guided saccades. These authors also proposed a mechanism by which ICMS-SEF could either shorten or delay saccade initiation depending on the state of oculomotor preparation at the time of ICMS-SEF.