Touchscreen cognitive testing: Cross-species translation and co-clinical trials in neurodegenerative and neuropsychiatric disease

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Neurobiology of Learning and Memory



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Translating results from pre-clinical animal studies to successful human clinical trials in neurodegenerative and neuropsychiatric disease presents a significant challenge. While this issue is clearly multifaceted, the lack of reproducibility and poor translational validity of many paradigms used to assess cognition in animal models are central contributors to this challenge. Computer-automated cognitive test batteries have the potential to substantially improve translation between pre-clinical studies and clinical trials by increasing both reproducibility and translational validity. Given the structured nature of data output, computer-automated tests also lend themselves to increased data sharing and other open science good practices. Over the past two decades, computer automated, touchscreen-based cognitive testing methods have been developed for non-human primate and rodent models. These automated methods lend themselves to increased standardization, hence reproducibility, and have become increasingly important for the elucidation of the neurobiological basis of cognition in animal models. More recently, there have been increased efforts to use these methods to enhance translational validity by developing task batteries that are nearly identical across different species via forward (i.e., translating animal tasks to humans) and reverse (i.e., translating human tasks to animals) translation. An additional benefit of the touchscreen approach is that a cross-species cognitive test battery makes it possible to implement co-clinical trials—an approach developed initially in cancer research—for novel treatments for neurodegenerative disorders. Co-clinical trials bring together pre-clinical and early clinical studies, which facilitates testing of novel treatments in mouse models with underlying genetic or other changes, and can help to stratify patients on the basis of genetic, molecular, or cognitive criteria. This approach can help to determine which patients should be enrolled in specific clinical trials and can facilitate repositioning and/or repurposing of previously approved drugs. This has the potential to mitigate the resources required to study treatment responses in large numbers of human patients.