Premature responses in the five-choice serial reaction time task reflect rodents’ temporal strategies: evidence from no-light and pharmacological challenges

Abstract

Rationale The five-choice serial reaction time task (5-CSRTT) is regularly used to study attention and impulsivity. In the 5-CSRTT, rodents initiate a trial, then after an inter-trial interval (ITI), a light appears in one of five holes. Responding in the lit vs. unlit hole reflects attention (accuracy), while responding prematurely before a light appears is suggested to reflect impulsivity/response disinhibition. Comparison of rat and mouse 5-CSRTT performance has raised questions on the validity of premature responses as measuring impulsivity/response inhibition. To minimize effort, rodents may use a temporal strategy, enabling their ‘timing’ of the ITI, minimizing the need to attend during this delay. Greater reliance this strategy could result in premature responses due to “guesses” if their timing was poor/altered. Objectives To assess the degree to which rats and/or mice utilize a temporal strategy, we challenged performance using infrequent no-light trials during 5-CSRTT performance. Results Even when no light appeared when one was expected, rats responded ~60% compared to ~40% in mice, indicating a greater reliance on a temporal strategy by rats than by mice. Consistent with this hypothesis, rats made more premature responses than mice. Additional studies using a temporal discrimination task and a 5-CSRTT variant demonstrated that delta-9-tetrahydrocannabinol, the active ingredient in cannabis, slowed temporal perception and reduced premature responses. Conclusions These data provide behavioral and pharmacological evidence indicating that premature responses are heavily influenced by temporal perception. Hence, they may reflect an aspect of waiting impulsivity, but not response disinhibition, an important distinction for translational clinical research.

Nicotine withdrawal-induced inattention is absent in alpha7 nAChR knockout mice

“…Mice then progressed to 8, 4, and 2 s SD trials when meeting the same criterion. Once at 2 s, a variable ITI (3–7 s) was introduced to limit the use of a temporally mediated strategy (Cope et al 2016) and increase the attentional load of the task. After reaching criterion, mice progressed to the 5C-CPT, in which target trials were the same as in the 5CSRTT (response required in a single lit hole) but non-target trials were added in which all 5 holes were illuminated (requiring the inhibition of responding), with the SD consistent between the two trial-types.…”

“…Secondary outcome variables include the responsivity index (RI) to represent bias of responding, as well as accuracy (the proportion of correct responses to incorrect responses), latencies to correct target responses (mean correct latency, MCL), total trials, the % of omitted trials, and the % of premature responses representing motoric impulsivity/temporal discrimination (Cope et al 2016). The calculation for each variable is thoroughly described elsewhere (Cope and Young 2016).…”

The Five‐Choice Continuous Performance Task (5C‐CPT): A Cross‐Species Relevant Paradigm for Assessment of Vigilance and Response Inhibition in Rodents

“…The premise that premature responses reflect motoric impulsivity has been questioned following performance comparisons between rats and mice (Fletcher et al, 2007; Young et al, 2013a; Cope et al, 2016). It has been suggested that premature responses could reflect an improper use of a temporal mediating strategy (Spratt et al, 2001).…”

The 5 choice continuous performance test (5C-CPT): A novel tool to assess cognitive control across species

“…Although these tests have high reliability and validity to measure these elements accurately in humans, there is dearth of cross-species translational neurocognitive tasks to measure these cognitive control elements, posing significant challenges for translational drug discovery. Cross-species neurocognitive tasks including the 5 Choice serial reaction time task (5CSRTT) and the sustained attention task (SAT) with and without distractor have been studied widely and validated to measure sustained attention, response selection and suppression and waiting impulsivity/timing in rodents (Cope et al, 2016; Humby et al, 2005; Robbins, 2002; McGaughy and Sarter, 1995). While these tasks measure several of the cognitive control elements mentioned above they are limited in their ability to measure response inhibition.…”

“…Once responding reliably, rodents are trained to respond to single target stimuli and inhibit from responding to non-target stimuli (Cope and Young, 2017). Once fully trained, rodents can then be challenged in various conditions to assess different cognitive control processes (e.g., distractibility; Young et al, 2011), described in detail in Cope et al, (2016a), with further details below.…”