M-USE: A Multi-task Platform for Profiling Cognitive and Motivational Constructs in Humans and Nonhuman Primates
Authors: Marcus R. Watson, Nathan Traczewski, Seema Dunghana, Kianoush Banaie Boroujeni, Adam Neumann, Xuan Wen, Thilo Womelsdorf (Vanderbilt University; Princeton). Preprint: bioRxiv 2023.11.09.566422 (doi 10.1101/2023.11.09.566422); mirrored in PMC as an NIH preprint-pilot record (PMC10680597, marked “not yet peer reviewed”). Predecessor station: Womelsdorf T, et al. (2021) “A Kiosk Station for the Assessment of Multiple Cognitive Domains and Cognitive Enrichment of Monkeys.” Front Behav Neurosci 15:721069.
Abstract
Background Understanding the neurobiological substrates of psychiatric disorders requires comprehensive evaluations of cognitive and motivational functions in preclinical research settings. The translational validity of such evaluations will be supported by (1) tasks with high construct validity that are engaging and easy to teach to human and nonhuman participants, (2) software that enables efficient switching between multiple tasks in single sessions, (3) software that supports tasks across a broad range of physical experimental setups, and (4) by platform architectures that are easily extendable and customizable to encourage future optimization and development.
New Method We describe the Multi-task Universal Suite for Experiments ( M-USE), a software platform designed to meet these requirements. It leverages the Unity video game engine and C# programming language to (1) support immersive and engaging tasks for humans and nonhuman primates, (2) allow experimenters or participants to switch between multiple tasks within-session, (3) generate builds that function across computers, tablets, and websites, and (4) is freely available online with documentation and tutorials for users and developers. M-USE includes a task library with seven pre-existing tasks assessing cognitive and motivational constructs of perception, attention, working memory, cognitive flexibility, motivational and affective self-control, relational long-term memory, and visuo-spatial problem solving.
Results M-USE was used to test NHPs on up to six tasks per session, all available as part of the Task Library, and to extract performance metrics for all major cognitive and motivational constructs spanning the Research Domain Criteria (RDoC) of the National Institutes of Mental Health.
Comparison with Existing Methods Other experiment design and control systems exist, but do not provide the full range of features available in M-USE, including a pre-existing task library for cross-species assessments; the ability to switch seamlessly between tasks in individual sessions; cross-platform build capabilities; license-free availability; and its leveraging of video-engine capabilities used to gamify tasks.
Conclusions The new multi-task platform facilitates cross-species translational research for understanding the neurobiological substrates of higher cognitive and motivational functions.
1. Introduction
Preclinical research aims to understand how neurophysiological, genetic, molecular, or cellular processes affect specific cognitive functions. Translating preclinical insights to clinical/neuropsychiatric contexts, and developing and evaluating treatments for specific disorders, requires assessing cognitive functions with high validity across human and animal models ( Kangas & Bergman, 2017; Redish et al., 2022). Research with nonhuman primates (NHPs) is an essential component of this research ( Oikonomidis et al., 2017; Palmer et al., 2021; Roelfsema & Treue, 2014; Scott & Bourne, 2022), because of the anatomical and functional similarities between human and NHP prefrontal cortex and its associated networks ( Passingham & Wise, 2012), which are implicated in many neuropsychiatric disorders..
Previous research has documented that the prefrontal cortex functions with the highest diagnostic value for neuropsychiatry include attention, cognitive flexibility, motivation, affective valuation, problem solving, and relational long-term memory ( Friedman & Robbins, 2022; Passingham, 2021). Existing task paradigms evaluate each of these in NHPs and humans ( Calapai et al., 2017; Friedman & Robbins, 2022; Oikonomidis et al., 2017; Perdue et al., 2018; Weed et al., 1999), providing domain-specific insights into the constructs that the National Institutes of Mental Health has summarized in their Research Domain Criteria (RDoC) as being central to advance our understanding of the neural correlates of neuropsychiatric disorders ( Aragona, 2014; Cuthbert & Insel, 2013; Morris & Cuthbert, 2012).
Assessing such functions across species has been spearheaded by the Cambridge Automated Neuropsychological Test Associated Battery (CANTAB, cf. Fray et al., 1996; Sahakian & Owen, 1992), that includes classical diagnostic tasks used for humans ( Langley et al., 2023) and NHPs (Monkey CANTAB, Lafayette Instrument Company, Lafayette, IN). These cross-species assessments have been instrumental for optimizing diagnostic testing, evaluating treatments, and advancing the pre-clinical understanding of neuropsychiatric disorders ( Friedman & Robbins, 2022; Palmer et al., 2021). However, while it is routine to assess multiple RDoC constructs in humans using test batteries like CANTAB ( Harvey, 2023; Langley et al., 2023), the MATRICS Consensus Cognitive Test Battery (MCCB), CogState ( Buchanan et al., 2011; Harvey, 2023), or CNTRICS ( Moore et al., 2013), in NHP the assessment of multiple cognitive domains has remained a major challenge with the majority of studies reporting results from one or few tests, and even fewer studies that allow automatized task switching during the assessment ( Berger et al., 2018; Calapai et al., 2017; Hassani et al., 2021; Hassani et al., 2023; Moore et al., 2003; Moore et al., 2005; Taffe et al., 2002; Weed et al., 1999; [Womelsdorf et al., 2021](https://www.biorxiv.