that early sensory EPs were equivalent for targets and distracters and therefore canceled out in the target minus distracter subtraction [17]. In contrast, in [25] target and distracter images were not interchanged to balance out sensory differences between the two images. Therefore, it is possible that the very early, post- saccade target versus distracter difference observed in [25] resulted from post saccadic modulations of sensory EPs relative to fixation rather than post-saccadic modulations of the P3 or object recognition processes. The observations that the significant target minus distracter difference in [25] occurred very early after saccade landing and had a topography uncharacteristic of the P3 could also be indications that the post saccade difference observed in [25] was a post-saccadic modulation of sensory EPs relative to fixation rather than post-saccadic modulations of the P3 or of object recognition processes. Saccadic P3 and BCIs The fact that the saccadic P3 was significant and reliably observed in all subjects that also had a significant fixation P3 indicates that the saccadic P3 is a robust signal that could be useful in BCIs. P3 start time, persistence and amplitude did not differ significantly in the saccade and fixation conditions. However, it should be noted that the P3 observed during natural eye movements could differ from the P3 observed here. Recall that the stimuli used herein were specifically designed to temporally restrict the moment of object recognition to occur after saccade landing. The rationale for allowing the target and distracter stimuli to only be distinguishable after saccadic landing was to restrict the time of object recognition in the saccade trials to the time period following saccadic landing. This restriction allowed for a direct comparison of the neural response time-locked to image presen- tation at fixation to the neural response time-locked to saccadic landing. In contrast, in natural viewing conditions, if object References 1. Henderson JM (2003) Human gaze control during real-world scene perception. Trends Cogn Sci 7: 498–504. 2. Hooge IT, Erkelens CJ (1999) Peripheral vision and oculomotor control during visual search. Vision Res 39: 1567–1575. 3. Burr D, Morrone M, Ross J (1994) Selective Suppression Of The Magnocellular Visual Pathway During Saccadic Eye-Movements. Nature: 511–513. 4. Ibbotson M, Krekelberg B (2011) Visual perception and saccadic eye movements. Curr Opin Neurobiol 21: 553–558. 5. Morrone M, Ross J, Burr D (2005) Saccadic eye movements cause compression of time as well as space. Nature Neuroscience: 950–954. 6. Ibbotson MR, Crowder NA, Cloherty SL, Price NS, Mustari MJ (2008) Saccadic modulation of neural responses: possible roles in saccadic suppression, enhancement, and time compression. J Neurosci 28: 10952–10960. 7. Ibbotson MR, Crowder NA, Price NS (2006) Neural basis of time changes during saccades. Curr Biol 16: R834–836. 8. Rajkai C, Lakatos P, Chen C, Pincze Z, Karmos G, et al. (2008) Transient cortical excitation at the onset of visual fixation. Cerebral Cortex: 200–209. 9. Reppas JB, Usrey WM, Reid RC (2002) Saccadic eye movements modulate visual responses in the lateral geniculate nucleus. Neuron 35: 961–974. 10. Cloherty SL, Mustari MJ, Rosa MG, Ibbotson MR (2010) Effects of saccades on visual processing in primate MSTd. Vision Res 50: 2683–2691. 11. Sylvester R, Haynes JD, Rees G (2005) Saccades differentially modulate human LGN and V1 responses in the presence and absence of visual stimulation. Curr Biol 15: 37–41. 12. Deubel H, Schneider W (1996) Saccade target selection and object recognition: Evidence for a common attentional mechanism. Vision Research: 1827–1837. 13. Hoffman J, Subramaniam B (1995) The role of visual attention in saccadic eye movements. Percept Psychophys 57: 787–795. 14. Medendorp WP, Goltz HC, Vilis T, Crawford JD (2003) Gaze-centered updating of visual space in human parietal cortex. J Neurosci 23: 6209–6214. 15. Gaarder K, Krauskopf J, Graf V, Kropfl W, Armington Jc (1964) Averaged Brain Activity Following Saccadic Eye Movement. Science 146: 1481–1483. 16. Dimigen O, Valsecchi M, Sommer W, Kliegl R (2009) Human microsaccade- related visual brain responses. J Neurosci 29: 12321–12331. 17. Johnson J, Olshausen B (2003) Timecourse of neural signatures of object recognition. Journal of Vision: 499–512. The Fixation and Saccade P3 recognition is partly achieved before saccadic landing, the saccadic P3 might be expected to be more temporally diffuse than the saccadic P3 observed here. Development of a P3-based BCI allowing natural eye movements might therefore necessitate similar constraints in the timing of image visibility relative to saccade landing that were enforced here, and/or further investigation to determine whether or not the properties of the saccadic P3 are altered based upon the degree of visibility of images prior to saccade landing. Another important aspect of the target and distracter stimuli was that they could be distinguished no matter where within the Gaussian envelopes the eyes landed, allowing for imprecision in eye position at saccadic landing without impacting the ability to distinguish targets from distracters. Therefore, subjects did not have to move their eyes after the initial saccadic landing to distinguish between target and distracter. A P3-based BCI allowing for natural eye movements would therefore need to employ similar constraints, and/or further investigation would be necessary to determine whether and how the saccadic P3 is altered if it is temporally distributed over the time course of multiple saccades. Given that humans move their eyes frequently, typically 2–3 times a second [1,2], a P3-based BCI allowing for eye movements could provide users with an intuitive method of brain controlled computer interaction. Acknowledgments Santhosh Palani kindly helped with Figure design. Author Contributions Conceived and designed the experiments: SD JD CP TC SK. Performed the experiments: SD. Analyzed the data: SD. Contributed reagents/ materials/analysis tools: SD JD CP TC SK. Wrote the paper: SD. 18. Donchin E, Spencer K, Wijesinghe R (2000) The mental prosthesis: Assessing the speed of a P300-based brain-computer interface. IEEE Transactions on Rehabilitation Engineering: 174–179. 19. Nijboer F, Sellers E, Mellinger J, Jordan M, Matuz T, et al. (2008) A P300-based brain-computer interface for people with amyotrophic lateral sclerosis. Clinical Neurophysiology: 1909–1916. 20. Parra L, Spence C, Gerson A, Sajda P (2005) Recipes for the linear analysis of EEG. Neuroimage: 326–341. 21. Hoffmann U, Vesin J, Ebrahimi T, Diserens K (2008) An efficient P300-based brain-computer interface for disabled subjects. Journal of Neuroscience Methods: 115–125. 22. Cooper R, Mccallum W, Newton P, Papakostopoulos D, Pocock P, et al. (1977) Cortical Potentials Associated With Detection Of Visual Events. Science: 74–77. 23. Dimigen O, Sommer W, Hohlfeld A, Jacobs AM, Kliegl R (2011) Coregistration of eye movements and EEG in natural reading: Analyses and review. J Exp Psychol Gen. 24. Marton M, Szirtes J, Breuer P (1985) Late Components Of Lambda Responses In Cognitive Tasks. Documenta Ophthalmologica: 199–204. 25. Kamienkowski JE, Ison MJ, Quiroga RQ, Sigman M (2012) Fixation-related potentials in visual search: A combined EEG and eye tracking study. J Vis 12. 26. Delorme A, Makeig S (2004) EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis. Journal of Neuroscience Methods: 9–21. 27. Dandekar S, Privitera C, Carney T, Klein SA (2012) Neural saccadic response estimation during natural viewing. J Neurophysiol 107: 1776–1790. 28. Yuval-Greenberg S, Tomer O, Keren AS, Nelken I, Deouell LY (2008) Transient induced gamma-band response in EEG as a manifestation of miniature saccades. Neuron 58: 429–441. 29. Engbert R, Kliegl R (2003) Microsaccades uncover the orientation of covert attention. Vision Res 43: 1035–1045. 30. Nichols TE, Holmes AP (2002) Nonparametric permutation tests for functional neuroimaging: a primer with examples. Hum Brain Mapp 15: 1–25. 31. Maris E, Oostenveld R (2007) Nonparametric statistical testing of EEG- and MEG-data. Journal of Neuroscience Methods: 177–190. 32. Medendorp WP, Kramer GF, Jensen O, Oostenveld R, Schoffelen JM, et al. (2007) Oscillatory activity in human parietal and occipital cortex shows PLOS ONE | www.plosone.org 13 November 2012 | Volume 7 | Issue 11 | e48761