Sleep deprivation impairs performance in the 5-choice continuous performance test: similarities between humans and mice

Abstract

Several groups undergo extended periods without sleep due to working conditions or mental illness. Such sleep deprivation (SD) can deleteriously affect attentional processes and disrupt work and family functioning. Understanding the biological underpinnings of SD effects may assist in developing sleep therapies and cognitive enhancers. Utilizing cross-species tests of attentional processing in humans and rodents would aid in mechanistic studies examining SD-induced inattention. We assessed the effects of 36h of: (1) Total SD (TSD) in healthy male and female humans (n=50); and (2) REM SD (RSD) in male C57BL/6 mice (n=26) on performance in the cross-species 5-choice continuous performance test (5C-CPT). The 5C-CPT includes target trials on which subjects were required to respond and non-target trials on which subjects were required to inhibit from responding. TSD-induced effects on human psychomotor vigilance test (PVT) were also examined. Effects of SD were also examined on mice split into good and poor performance groups based on pre-deprivation scores. In the human 5C-CPT, TSD decreased hit rate and vigilance with trend-level effects on accuracy. In the PVT, TSD slowed response times and increased lapses. In the mouse 5C-CPT, RSD reduced accuracy and hit rate with trend-level effects on vigilance, primarily in good performers. In conclusion, SD induced impaired 5C-CPT performance in both humans and mice and validates the 5C-CPT as a cross-species translational task. The 5C-CPT can be used to examine mechanisms underlying SD-induced deficits in vigilance and assist in testing putative cognitive enhancers.

Keywords: 5-Choice Continuous Performance Test; 5-Choice Serial Reaction Time Task; 5C-CPT; 5CSRTT; Attention; Bipolar disorder; CPT; CR; Correct rejection; FA; FA rate; FAR; False alarm; HR; Hit rate; ITI; Inter-trial interval; PVT; Psychomotor Vigilance Test; Psychomotor vigilance test; REM; REM sleep deprivation; RI; RSD; RT; Rapid eye movement; Reaction time; Responsivity index; SD; Sleep deprivation; TSD; Total sleep deprivation; Vigilance; vRT; variable RT.

Figure 1. Schematic of the human and mouse 5C-CPT

In both the human and mouse 5C-CPTs, there are 5 stimuli locations. For humans, stimuli are presented in 1 of 5 locations arrayed in an arc on a computer screen, and subjects respond using a 5-way joystick (A). For mice, stimuli are presented in 1 of 5 holes located in an arc at the rear of a 5-hole operant chamber and responses are recorded by infrared beams in each hole (B). The task design is the same in both cases, whereby: 1) a single stimulus represents a target trial to which subjects must respond; and 2) all 5 stimuli being presented simultaneously represents a non-target trial to which the subject must inhibit from responding. Target trials generate measures of hits and misses (target responses and omissions), which are used to calculate a subjects’ hit rate, while non-target trials generate measures of correct rejections and false alarms, which are used to calculate a subjects’ false alarm rate. Using signal detection theory (SDT), the non-parametric measure of vigilance (d′) and bias (responsivity index (RI)) are generated. The table provides examples of what permutations of hit and false alarm rates result in various d′ and RI levels and its interpretation.

Figure 2. Effects of TSD on 5C-CPT performance in humans

TSD impaired vigilance as measured by reduced d′ (a) with a large effect size (Cohen’s d = 0.6). This TSD-impaired vigilance was partially driven by reduced overall hit rate (b; Cohen’s d effect size = 0.5) and lower non-target responses (c; Cohen’s d effect size = 0.15). Humans during TSD were slightly less responsive (d) and also made slightly less target responses (e) compared to humans after normal sleep. No significant difference between normal sleep and TSD was observed on the number of omitted trials (f). Mean RTs did not differ (g), but humans during TSD exhibited slight increased variable RTs compared to humans after normal sleep (h). Data are presented as the mean ± SEM, *denotes p<0.05 when compared with humans after normal sleep.

Figure 3. Effects of RSD on 5C-CPT performance in all C57BL/6 mice

RSD had only subtle effects when looked at the overall group performance of mice in the 5C-CPT. Overall, mice seemed to perform better with longer stimulus duration (a-h). However, this effect was less pronounced in mice during RSD, where RSD decreased hit rate (b) and increased the amount of omissions (f) at the longest stimulus duration of 2 s. Data are presented as the mean ± SEM, *denotes p<0.05 when compared with mice after normal sleep.

Figure 4. Effects of RSD on 5C-CPT performance in good performing mice

In the good performing subgroup of mice, RSD more severely impaired 5C-CPT performance. RSD negatively impacted vigilance as measured by slight reduced d′ at the 1.25 s stimulus duration (a). RSD decreased hit rate, specifically at the 0.75 s and 2 s stimulus durations (b), while leaving non-target responses unaffected (c). No effect of RSD was observed on responsiveness (d), but after RSD, mice made fewer target responses compared to mice after normal sleep, specifically at the 0.75 s stimulus duration (e). Although longer stimulus durations reduced the number of omitted trials in control mice, this effect was less pronounced in the mice after RSD, where RSD increased omissions at the highest stimulus duration (f). No effect of RSD was observed on both mean and variable RTs (g-h). Data are presented as the mean ± SEM, *denotes p<0.05 when compared with mice after normal sleep.