Abstract

BackgroundAttentional dysfunction is related to functional disability in patients with neuropsychiatric disorders such as schizophrenia, bipolar disorder, and Alzheimer's disease. Indeed, sustained attention/vigilance is among the leading targets for new medications designed to improve cognition in schizophrenia. Although vigilance is assessed frequently using the continuous performance test (CPT) in humans, few tests specifically assess vigilance in rodents.MethodsWe describe the 5-choice CPT (5C-CPT), an elaboration of the 5-choice serial reaction (5CSR) task that includes non-signal trials, thus mimicking task parameters of human CPTs that use signal and non-signal events to assess vigilance. The performances of C57BL/6J and DBA/2J mice were assessed in the 5C-CPT to determine whether this task could differentiate between strains. C57BL/6J mice were also trained in the 5CSR task and a simple reaction-time (RT) task involving only one choice (1CRT task). We hypothesized that: 1) C57BL/6J performance would be superior to DBA/2J mice in the 5C-CPT as measured by the sensitivity index measure from signal detection theory; 2) a vigilance decrement would be observed in both strains; and 3) RTs would increase across tasks with increased attentional load (1CRT task<5CSR task<5C-CPT).ConclusionsC57BL/6J mice exhibited superior SI levels compared to DBA/2J mice, but with no difference in accuracy. A vigilance decrement was observed in both strains, which was more pronounced in DBA/2J mice and unaffected by response bias. Finally, we observed increased RTs with increased attentional load, such that 1CRT task<5CSR task<5C-CPT, consistent with human performance in simple RT, choice RT, and CPT tasks. Thus we have demonstrated construct validity for the 5C-CPT as a measure of vigilance that is analogous to human CPT studies.

Highlights

  • The link between cognitive performance and global functioning/quality of life has been established in numerous disorders including schizophrenia, bipolar disorder, attention deficit hyperactivity disorder, and Alzheimer’s disease [1,2]

  • Baseline 5C-continuous performance test (CPT) strain comparison Once trained in the 5-choice CPT (5C-CPT), the performance of C57BL/6J

  • There was a trend towards increased %Omissions in DBA/2J compared to C57BL/6J mice (F(1,5) = 5.0, p = 0.076; Fig 2B)

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Summary

Introduction

The link between cognitive performance and global functioning/quality of life has been established in numerous disorders including schizophrenia, bipolar disorder, attention deficit hyperactivity disorder, and Alzheimer’s disease [1,2]. Mackworth [4], pioneered the formal assessment of vigilance in humans, where subjects were required to discriminate between signal and non-signal (noise) stimuli in their environment. This discrimination is often operationally defined as requiring a response to Signals and inhibiting responses to Noise. On trials were only Noise is present correctly withholding a response is referred to as a ‘‘Correct Rejection’’ (CR) while an erroneous response is a ‘‘False Alarm’’ (FA) (see table 1) In many cases these parameters are expressed as proportions to aid calculation so for example perfect performance would be characterized as a p(Hit) = 1.0, p(Miss) = 0, p(CR) = 1.0 and p(FA) = 0. Vigilance is assessed frequently using the continuous performance test (CPT) in humans, few tests assess vigilance in rodents

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