EEG in Cognitive Tasks in Preclinical Models As Translational Biomarker

Background: There is a pressing need for translational tests of cognitive functioning that demonstrate consistent neurophysiological biomarkers across species. While preclinical studies provide numerous therapeutic targets for neuropsychiatric disorders, the failure to convert these to clinical treatments highlight that behavioral similarity alone is insufficient. Biomarkers of brain function are needed. As part of an ongoing project, we recently integrated tasks measuring specific Research Domain Criteria (RDoC) with electroencephalography (EEG) in mouse and human subjects to directly compare neural activity across species. Despite the procedural differences (e.g., training in touchscreens for mice, instructions and a joystick in humans), psychometric and neural biomarker signatures of performance were consistent across species.

Methods: Humans were tested in a variety of behavioral paradigms including the probabilistic learning task (PLT) progressive ratio breakpoint task (PRBT), and 5-choice continuous performance task (5C-CPT), while neural electroencephalogram (EEG) recording was conducted. Similarly, C57BL/6J mice performed touch-screen analogs of these paradigms while or dura-resting EEG-like signal was recorded for direct comparable analysis.

Results: During PLT performance we observed that frontal Reward Positivity scaled with the degree of positive prediction error, varying in strength according to probability ratio in both humans and mice. On the PRBT we observed parietal alpha power was elevated as both humans and mice neared their breakpoint. In the 5C-CPT, performance varied based on task difficulty in both humans and mice and post response EEG stimuli exhibit consistencies across species.

Discussion: We demonstrated the capability of utilizing identical methods for investigating rodent neuronal activity performing the same behavioral tasks available in rats and humans, in cognitive control, effortful motivation, and reward learning. Current studies will determine whether psychopharmacological challenges alter EEG signaling consistently across humans and rodents. These techniques provide important information regarding the validity rodent models to neural circuitry of behaviors relevant to psychiatry in addition to the likelihood of translating drug-induced changes in performance across species.