Pupil size tracks perceptual content and surprise Niels A. Kloosterman, 1,2 Thomas Meindertsma, 1,2,3 Anouk M. van Loon, 1,2,4 Victor A. F. Lamme, 1,2 Yoram S. Bonneh 5 and Tobias H. Donner 1,2,6 1 Department of Psychology, University of Amsterdam, Weesperplein 4, Amsterdam, 1018XA, the Netherlands 2 Amsterdam Center for Brain and Cognition, Institute for Interdisciplinary Studies, University of Amsterdam, Amsterdam, the Netherlands 3 Department of Neurophysiology and Pathophysiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 4 Department of Cognitive Psychology, Vrije Universiteit, Amsterdam, the Netherlands 5 Department of Human Biology, University of Haifa, Haifa, Israel 6 Bernstein Center for Computational Neuroscience, Charit e-Universit€ atsmedizin, Berlin, Germany Keywords: brain state, human, perceptual bistability, perceptual decision-making, pupillometry Abstract Changes in pupil size at constant light levels reflect the activity of neuromodulatory brainstem centers that control global brain state. These endogenously driven pupil dynamics can be synchronized with cognitive acts. For example, the pupil dilates during the spontaneous switches of perception of a constant sensory input in bistable perceptual illusions. It is unknown whether this pupil dilation only indicates the occurrence of perceptual switches, or also their content. Here, we measured pupil diameter in human subjects reporting the subjective disappearance and re-appearance of a physically constant visual target surrounded by a moving pattern (‘motion-induced blindness’ illusion). We show that the pupil dilates during the perceptual switches in the illusion and a stimulus-evoked ‘replay’ of that illusion. Critically, the switch-related pupil dilation encodes perceptual content, with larger amplitude for disappearance than re-appearance. This difference in pupil response amplitude enables prediction of the type of report (disap- pearance vs. re-appearance) on individual switches (receiver-operating characteristic: 61%). The amplitude difference is indepen- dent of the relative durations of target-visible and target-invisible intervals and subjects’ overt behavioral report of the perceptual switches. Further, we show that pupil dilation during the replay also scales with the level of surprise about the timing of switches, but there is no evidence for an interaction between the effects of surprise and perceptual content on the pupil response. Taken together, our results suggest that pupil-linked brain systems track both the content of, and surprise about, perceptual events. Introduction It has long been known that the diameter of one’ s pupil changes during cognitive acts (Hess & Polt, 1964; Kahneman & Beatty, 1966). Specifically, the pupil dilates when subjects engage in cogni- tive tasks, independent of the level of retinal illumination (Einhauser et al., 2010; Preuschoff et al., 2011; Fiedler & Glockner, 2012; Wierda et al., 2012; Zylberberg et al., 2012; Shalom et al., 2013; de Gee et al., 2014). These pupil responses are associated with changes in the gain of neural interactions in the cerebral cortex (El- dar et al., 2013; Reimer et al., 2014). Indeed, mounting evidence suggests that the same brainstem centers that control fast changes in cortical state also control non-luminance-mediated pupil dynamics – in particular the noradrenergic system (Aston-Jones & Cohen, 2005; Murphy et al., 2014). Other brainstem systems such as the choliner- gic system (Sarter et al., 2009; Lee & Dan, 2012; Yu, 2012) and the superior colliculus (Wang et al., 2012) involved in attentional con- trol may also contribute to task-related pupil dynamics. Task-related pupil responses, therefore, provide a window into fast fluctuations in global brain state during cognitive processing. In particular, the pupil dilates during illusory perceptual switches in so-called multi-stable perceptual phenomena, in which a constant sen- sory input induces illusory switches in perception (Einhauser et al., 2008; Hupe et al., 2009; Frassle et al., 2014). Similar dilation occurs during the stimulus-evoked replay of the perceptual switches (Einhaus- er et al., 2008; Hupe et al., 2009; Frassle et al., 2014). While the but- ton press typically used for reporting the perceptual switches can account for part of the pupil dilation, significant dilation remains in the absence of any overt motor response (Hupe et al., 2009). Here, we asked whether the switch-related pupil dilations only track the occurrence of perceptual switches, or if they also contain information about the content of perception. In some illusions, per- ception alternates between two asymmetric states. For example, in ‘motion-induced blindness’ (MIB), a salient visual target surrounded by a moving mask spontaneously disappears from perception, and then reappears after some time (Bonneh et al., 2001, 2014; Bonneh & Donner, 2011). This subjective target disappearance and Correspondence: Dr N. A. Kloosterman, as above. E-mail: niels.kloosterman@gmail.com Received 19 August 2014, revised 14 January 2015, accepted 26 January 2015 © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd European Journal of Neuroscience, pp. 1–11, 2015 doi:10.1111/ejn.12859