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 36 hours 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.

GlyT-1 Inhibition Attenuates Attentional But Not Learning or Motivational Deficits of the Sp4 Hypomorphic Mouse Model Relevant to Psychiatric Disorders

“…Training and testing took place in four 5-hole operant chambers (25 × 25 × 25 cm; Med Associates, St Albans, VT) consisting of an array of five square holes (2.5 × 2.5 × 2.5 cm) arranged horizontally on a curved wall 2.5 cm above the grid floor ( Figure 1a) as described elsewhere (van Enkhuizen et al, 2013). This array was opposite a food delivery magazine (Lafayette Instruments, Lafayette, IN) located at floor level with a house light located near the ceiling.…”

Animal Paradigms to Assess Cognition with Translation to Humans

“…This differs from the 5-CSRTT, since in the 5-CSRTT a rodent does not need to inhibit a response; therefore the 5C-CPT is similar to the human CPT. Thus far, sleep deprivation experiments have demonstrated the use of this task in both mice and humans, and potential future pharmacological and/or lesion experiments may affirm the usefulness of this new task as a translatable paradigm (van Enkhuizen et al 2014). …”

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

“…Across species translational potential of this task, stemmed from the development of the human 5C-CPT (McKenna et al, 2013; Young et al, 2013). Further evidence of construct validity for this task came from, 36-hour sleep deprivation studies in mice and humans showing similar cross-species impairment in task performance (van Enkhuizen et al, 2014), and human fMRI studies demonstrating parietal cortical involvement (McKenna et al, 2013), mirroring lesions studies demonstrating the need for parietal cortices (van Enkhuizen et al, 2015). Here we review the rodent and human 5C-CPT, methodological challenges, adaptations, and applications of this task for potential TS and ADHD research.…”

“…The human 5C-CPT results in brain region-specific activation that is consistent with other CPTs (McKenna et al, 2013). In addition, sleep deprivation impairs 5C-CPT similarly to other CPTs (van Enkhuizen et al, 2014). More importantly, the 5C-CPT is clinically sensitive, as demonstrated by deficits in schizophrenia patients compared to healthy participants (Young et al, 2013), with biomarker signatures (Young et al, 2017).…”