A novel multichoice touchscreen paradigm for assessing cognitive flexibility in mice

Abstract

Cognitive flexibility refers to various processes which enable behaviors to be modified on the basis of a change in the contingencies between stimuli or responses and their associated outcomes. Reversal learning is a form of cognitive flexibility which measures the ability to adjust responding based on a switch in the stimulus–outcome contingencies of, typically two, perceptually distinct stimuli. Reversal tasks have provided valuable insight into the neural basis of cognitive flexibility, implicating brain regions including the lateral orbitofrontal cortex (lOFC) and dorsomedial prefrontal cortex (dmPFC). However, with two-stimulus reversal, it is difficult to determine whether response errors are due excessive perseveration, deficient learning, or other problems with updating. To address this limitation, we developed a mouse three-choice touchscreen-based visual reversal task, in which the contingencies of two stimuli were switched on reversal but a third, simultaneously presented, stimulus was never reinforced. We found that, in male C57BL/6J mice, responding at the previously rewarded stimulus predominated over the newly and never-reinforced stimuli during early reversal. Next, we showed that acute pharmacological inhibition of lOFC, but not dmPFC, impaired early reversal performance, relative to noninactivated controls. Interestingly, however, lOFC inactivation deficits were characterized by increased choice of the never-reinforced stimulus and a decrease in (perseverative-like) responding at the previously rewarded stimulus. These effects are inconsistent with the historical notion of lOFC mediating response inhibition and closer to recent views of the lOFC's role in response/outcome tracking. Overall, these findings provide initial support the utility of this novel paradigm for studying cognitive flexibility and its underlying neural substrates.

Dopamine D2-like receptor stimulation blocks negative feedback in visual and spatial reversal learning in the rat: behavioural and computational evidence

“…Our paradigm thus provides a novel method for studying stimulus perseveration (inhibiting the response at the previously rewarded stimulus, A−) and learned non-reward (approaching a previously non-rewarded stimulus, B+) in visual reversal learning, and builds upon previous work addressing these phenomena using e.g. three response options or replacement of one of the stimuli with a novel stimulus during the reversal phase (Alsiö et al 2015; Clarke et al 2007; Piantadosi et al 2019); for a review, see (Nilsson et al 2015). A selective blockade of learning from negative feedback, as reported here, is in agreement with previous findings of quinpirole-induced delays in overcoming perseverative responding at the previously correct response option in spatial reversal learning (Boulougouris et al 2009).…”

Sex-dependent effects of chronic intermittent voluntary alcohol consumption on attentional, not motivational, measures during probabilistic learning and reversal

“…Although not significant, we found a trend for a main effect of sex [F (1,14) Learning data were analyzed separately, subdivided into pretraining, discrimination, and reversal phases. Early vs. late discrimination and reversal learning based on prior studies indicating these may be particularly informative to contrast [39][40][41][42][43][44]. Females exhibited more high-drinking (5-10 g/kg/24 hr) days than males.…”

Critical mass: The rise of a touchscreen technology community for rodent cognitive testing

“…The rise in popularity of touchscreen technology for cognitive behavioral testing in rodent neuroscience research suggests that accumulating knowledge and collaborating through an annual or biennial symposium, twice‐yearly hands‐on training course and through our virtual community on https://touchscreencognition.org/ ensures that common issues can be addressed which can further improve standardized testing. Some of these issues involve optimizing touchscreen systems such as the hardware, 47 and development of new touchscreen tasks which is easily achievable because of the flexibility of the touchscreen systems 15,48,49 . For example, Piantadosi et al 48 have developed a novel multichoice task for assessing cognitive flexibility.…”

“…Some of these issues involve optimizing touchscreen systems such as the hardware, 47 and development of new touchscreen tasks which is easily achievable because of the flexibility of the touchscreen systems 15,48,49 . For example, Piantadosi et al 48 have developed a novel multichoice task for assessing cognitive flexibility. The multichoice paradigm allows researchers to further tease apart whether response errors are because of perseveration, inability to learn or other issues with updating.…”