Validation of electrophysiological biomarkers associated with performance in a preclinical assay of sustained attention

PROJECT SUMMARY Sustained attention, the ability to focus on an activity or stimulus over time, is impaired in many brain disorders. Targeting attentional deficits for treatment is critical because these symptoms are negatively correlated with functional outcome and quality of life. Continuous performance tests (CPTs) have been designed to measure sustained attention in multiple species. Similar neural circuits are engaged in both humans and model organisms during CPT performance, supporting their use in translational studies that screen for novel therapeutics. The prelimbic cortex (PrL), is involved in both conflict detection and allocation of attention to cues before orientation, important components in go/no-go tasks like CPTs. Electroencephalogram (EEG) studies in humans show that neural activity in the dorsal anterior cingulate cortex (dACC), which shows functional and anatomical analogy to the rodent PrL, is correlated with task engagement and performance in the CPT. In this application, we optimize the rCPT to determine the effect of target percentage on the time-on-task vigilance decrement. We then evaluate the optimized CPT paradigm by assessing the impact of amphetamine, a known enhancer of performance, on the electrophysiological correlates of behavior. Finally, we mechanistically test the role of neural activity in the PrL-LC circuit in controlling behavioral performance and electrophysiological correlates in the optimized rCPT.