Bridging the bench to bedside gap: validation of a reverse-translated rodent continuous performance test using functional magnetic resonance imaging

Vigilance, which requires attending to relevant while ignoring irrelevant stimuli, is a cognitive domain impacted by schizophrenia and bipolar disorder. Various continuous performance tests (CPT) have been used to examine neural correlates of vigilance within people with and without severe mental illness, though there are limited cross-species paradigms available. The 5-choice CPT (5C-CPT) was designed for use in rodents as a cross-species translational paradigm. Here, we evaluate construct validity of a reverse-translated human analog of the 5C-CPT in assessing the neural correlates of vigilance. Functional magnetic resonance imaging during the 5C-CPT was used to examine activation of healthy individuals during target and non-target trials separately. We found activation in brain regions implicated in sustained attention processes including premotor cortex, inferior parietal lobe, basal ganglia, and thalamus during target trials. For non-target trials, we found expected activation in inferior frontal cortex, premotor cortex, presupplementary motor area, and inferior parietal lobe. Results support the construct validity of the 5C-CPT in measuring attentional and inhibitory systems within a single task paradigm enabling the assessment of vigilance across species. This task can be used for powerful parallel human and animal investigations of the biological basis of vigilance deficits in populations with severe mental illness.