Reverse translated and gold standard continuous performance tests predict global cognitive performance in schizophrenia

Abstract

Attentional dysfunction contributes to functional impairments in schizophrenia (SZ). Sustained attention is typically assessed via continuous performance tasks (CPTs), though many CPTs have limited cross-species translational validity and place demands on additional cognitive domains. A reverse-translated 5-Choice Continuous Performance Task (5C-CPT) for human testing—originally developed for use in rodents—was designed to minimize demands on perceptual, visual learning, processing speed, or working memory functions. To-date, no studies have validated the 5C-CPT against gold standard attentional measures nor evaluated how 5C-CPT scores relate to cognition in SZ. Here we examined the relationship between the 5C-CPT and the CPT-Identical Pairs (CPT-IP), an established and psychometrically robust measure of vigilance from the MATRICS Consensus Cognitive Battery (MCCB) in a sample of SZ patients (n = 35). Relationships to global and individual subdomains of cognition were also assessed. 5C-CPT and CPT-IP measures of performance (d-prime) were strongly correlated (r = 0.60). In a regression model, the 5C-CPT and CPT-IP collectively accounted for 54% of the total variance in MCCB total scores, and 27.6% of overall cognitive variance was shared between the 5C-CPT and CPT-IP. These results indicate that the reverse translated 5C-CPT and the gold standard CPT-IP index a common attentional construct that also significantly overlaps with variance in general cognitive performance. The use of simple, cross-species validated behavioral indices of attentional/cognitive functioning such as the 5C-CPT could accelerate the development of novel generalized pro-cognitive therapeutics for SZ and related neuropsychiatric disorders.

Neurocognitive and Perceptual Processing in Genetic Mouse Models of Schizophrenia: Emerging Lessons

“…This may lead to valid hypotheses about brain function that will in turn guide experiments at the neural substrate level. In addition, reverse-translation by adapting cognitive tasks from animal research to human clinical settings is a complementary approach that may start offering links between animal findings in the behavioral and neural substrate level and human symptoms (Bismark and others 2018).…”

Convergent neural substrates of inattention in bipolar disorder patients and dopamine transporter‐deficient mice using the 5‐choice CPT

“…Although BD is characterized by complex and multifaceted symptoms including elevated mood, patients who show cognitive deficits have poorer functional outcome . One dominant symptom of BD is inattention, recognized as core to cognitive deficits across psychiatric conditions . The development of pro‐attentive therapies will likely lead to more generalized cognitive improvement.…”

“…3 One dominant symptom of BD is inattention, 4 recognized as core to cognitive deficits across psychiatric conditions. 5,6 The development of pro-attentive therapies will likely lead to more generalized cognitive improvement. Unfortunately, no targeted pro-attentive treatments have been established, [7][8][9] in part due to our limited understanding of the neural systems underlying this deficit.…”

Amphetamine improves mouse and human attention in the 5-choice continuous performance test

“…The 5C-CPT retains this format for target trials but – consistent with human CPTs – additionally includes non-target trials to which subjects must inhibit from responding. Further, the task has been reverse-translated for human testing and validated in clinical populations that exhibit task deficits (Young et al, 2013) comparable to those observed with traditional CPT variants (Bismark et al, In Press; Cornblatt and Keilp, 1994).…”