Brigman et al. Figure 2 | Mouse behavioral assays for cognitive ﬂexibility. (A) Intra-dimensional/extra-dimensional digging task. Mice are trained to dig for food reward using either olfactory (digging medium odor) or tactile (digging medium texture) cues.The rewarded cue in the same dimension is switched to test for intra-dimensional shifting.The rewarded cue is changed to the different dimension to test for extra-dimensional shifting. (B) Spatial reversal in Morris water maze. After learning to locate a submerged platform using distal spatial cues (see Figure 1E), the platform location is moved to the opposite side of the pool to test for reversal. (C) Spatial reversal inT-maze. After learning to locate a food reward in one goal arm using distal spatial cues, the rewarded goal arm is switched to test for reversal. (D) Reversal of discriminated operant response in a bar-pressing system. After learning to press a lever for reward based on a visual (e.g., light) or spatial (lever location) cue, the rewarded cue is switched to test for reversal. (E) Reversal of discriminated operant response in a touchscreen-based system. Reversal of a discriminated operant response can also be tested using a touchscreen-based system (for details, see Figure 3). Touchscreen-based operant system A system in which rats and mice learn to discriminate and reverse between two visual stimuli projected onto a touch-sensitive computer screen. It provides a procedure more analogous and comparable to reversal tasks employed in human subjects. Can be readily modiﬁed to test for a battery of cognitive and executive functions. 22 | May 2010 | Volume 4 | Issue 1 executive functions, including attention, working memory and response inhibition (Roberts, 2006). In addition, reversal learning paradigms allow for a direct measure of perseverative responding to a previously rewarded stimuli or cue, as it is present, but unrewarded, during the reversal phase. This is particularly pertinent because per- severation, possibly caused by insensitivity to negative feedback (i.e., non-reward) following incorrect responding, is a feature of impaired reversal in schizophrenia (Leeson et al., 2009). TOUCHSCREEN-BASED MEASURE OF REVERSAL LEARNING IN MICE Various tasks have been developed to measure reversal in rats and mice in maze (Mackintosh et al., 1968; Ragozzino et al., 1999; Stefani et al., 2003; Floresco et al., 2008) as well as operant settings (e.g., Ferry et al., 2000; Schoenbaum et al., 2000; Bohn et al., 2003a,b; Schoenbaum et al., 2004) (Figures 2B–D). In an effort to pro- vide a procedure that was more analogous and comparable to reversal tasks being employed in patients (Robbins et al., 1994) and higher species (non-human primates), Bussey and colleagues established a touchscreen-based operant sys- tem in which rats and mice learn to discriminate and reverse between two visual stimuli projected onto a touch-sensitive computer screen (Bussey et al., 1994, 2001) (Figure 2E). Demonstrating the translatable potential for mapping mouse studies onto systems in the human, reversal per- formance in this system is PFC-dependent, as conﬁrmed by lesion studies in the rat (Bussey et al., 1997; Chudasama and Robbins, 2003) and to some extent in the mouse (Brigman and Rothblat, 2008). In addition to its comparability to human measures of reversal, this paradigm has several unique beneﬁts (for discussion, see Bussey et al., 2008). Of note, the automation of the task makes it relatively free of experimenter inﬂuences that can vary across individuals and laboratories, and inﬂuence results (Crabbe et al., 1999). The system www.frontiersin.org