S-ketamine influences strategic allocation of attention but not exogenous capture of attention
Introduction
In the current study, we tested whether s-ketamine impacts on strategic covert attention shifts away from a cue. S-ketamine is an N-methyl-D-aspartate (NMDA) receptor blocker (Oye et al., 1992, Vollenweider et al., 1997). S-ketamine is known to alter a variety of eye movements, including anti-saccades where participants make a saccade to a location opposite of the target (Radant, Bowdle, Cowley, Kharasch, & Roy-Byrne, 1998). Such performance decrements have been ascribed to metabolic changes in prefrontal regions and the frontal eye fields of the human cortex that are involved in the control of eye movements (Brier et al., 1997, O’Driscoll et al., 1995). In addition, s-ketamine also blocks NMDA receptors within the Superior Colliculi of the mid-brain (SC; cf. Dumanskaya et al., 2012, Phongphanphanee et al., 2008; see also Grossberg, Roberts, Aguilar, & Bullock, 1997). The SC also play an active role in shifting visual attention, steering saccades, and inhibiting of attention shifts back to a previously attended (or cued) position (Dorris et al., 2002, Everling et al., 1999, Fecteau et al., 2004, Sapir et al., 2001).
On the basis of these findings and a known strong overlap between brain areas underlying saccadic control and covert attentional shifts (Nobre, Gitelman, Dias, & Mesulam, 2000), we used a cueing task to test whether s-ketamine would also alter covert attention shifts elicited by an ‘anti-predictive cue’ (see below). Generally, studies of s-ketamine effects on covert attention are rare, but Gouzoulis-Mayfrank, Heekeren, Neukirch, Stoll, Stock, Daumann, et al. (2006), for example, reported effects on visual attention in a cueing task. These authors found lower inhibition of return (IOR) after s-ketamine. Typically, with a short cue-target interval, cues at the same position (SP) as the target lead to faster Reaction Times (RTs) than cues at a different position (DP) than the target (Posner, 1980). However, when the cue-target interval exceeds 200–300 ms, this effect reverses to faster RTs in the DP than the SP condition, an effect referred to as IOR (Klein, 2000, Posner and Cohen, 1984). IOR has been ascribed to deallocation of attention away from the cue associated with active suppression of the cued position (but see Hu et al., 2011, Lupiàñez, 2010).
IOR is typically only observed with long cue-target intervals and following non-predictive cues – that is, cues which do not inform about the most likely target position. In contrast to IOR, an anti-predictive cue elicits a similarly looking pattern of RTs – lower RTs in DP than SP conditions – but with a much shorter cue-target interval. Anti-predictive cues indicate that the target is presented at a specific DP position, so that the participants should strategically shift their attention away from the cue and toward the likely target position. Critically, DP-to-SP RT advantages with anti-predictive cues can already be found with a cue-target interval as short as 16 ms but only if the participant can clearly see the cues (see Experiment 5 of Fuchs & Ansorge, 2012a). To note, 16 ms are too short a time to elicit even the fastest saccades. Hence, the reversed cueing effect with anti-predictive cues reflects a rapid strategic covert attention shift and forms an ideal test bed for our research question.
Section snippets
Experiment 1
The main goal of the present experiment was to investigate whether s-ketamine affects strategic attention shifts away from a clearly visible anti-predictive cue. To this aim, we tested the same participants twice, once under s-ketamine and once under placebo (NaCl) treatment. In each trial, our participants had to search for a target that was presented in 80% of all trials. The target was presented equally often to the left or to the right of fixation. Prior to the target a cue was shown. It
Experiment 2
In Experiment 2, we set out to test the general nature of the difference between the less visible and the more visible cueing conditions of Experiment 1. This question concerns the influence of two confounding variables – the lower versus higher visibility of the cues that was confounded with the presence versus absence of placeholders. This question can be studied independently of the s-ketamine administration. In past studies and Experiment 1, placeholders were only present in the less
General discussion
Our results speak for a very early selective influence of s-ketamine on the strategic use of anti-predictive cues. The better visible cues that were presented without placeholders (in Experiment 1) allowed much more strategic shifting of covert attention to the cue’s opposite side (of 45 ms) than the less visible cues that were presented with placeholders (7 ms). Exactly this strategic shifting to the opposite side was affected by s-ketamine to a stronger degree in better visible than less
Conclusion
Although the exact neuronal underpinnings still await specification, the present study supports the assumption that s-ketamine plays an active role in strategic attention shifts away from a stimulus. The novel finding is that s-ketamine eliminates strategic covert attention shifts away from a peripheral cue in a short cue-target interval. However, s-ketamine’s influence seems to be absent with exogenous attention capture.
Acknowledgments
Thanks to Isabell Möckel, Alexander Kudrna, Maximilian Stein, and Alex Feleki for help with the data collection. This research was partly funded by Austrian National Bank Grant P 14193. The authors are grateful to the staff at the Department of Psychiatry and Psychotherapy for medical and technical support, especially to D. Winkler, G. Kranz, A. Hahn, P. Baldinger.
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