Biology subjects

Asch, P. A.

Publications and source records attributed to Asch, P. A..

5 recordsLinked to original sources

bioRxiv2026

A Scalable Touchscreen-Based Spatial Working Memory Task for Cross-Species Research

The common marmoset is rapidly emerging as a powerful nonhuman primate model in neuroscience, yet the development of scalable, mechanistically informative cognitive paradigms has lagged behind advances in neural recording and genetic tools. Here, we introduce and validate a touchscreen-based spatial working memory task designed for direct cross-species translation between marmosets and humans. The paradigm independently manipulates retention delay and spatial separation between test choice stimuli, enabling parametric control over maintenance and interference demands within a single framework. Twelve marmosets and seventy-one human participants performed a Delayed Non-Match-to-Position task in which memory delay (1, 5, 10 seconds) and angular separation between target and distractor locations were systematically varied. Across species, accuracy declined as delay increased and as spatial separation decreased, demonstrating robust sensitivity to both maintenance demands and similarity-based interference. Critically, delay and separation interacted in both species, indicating that these had additive effects. Choice latency analyses further supported interpretation of performance, with slower responses on incorrect trials in both groups. Together, these findings establish a scalable and translationally aligned spatial working memory paradigm that captures interacting maintenance and interference processes. This task provides a powerful platform for circuit-level investigation and offers a sensitive cognitive assay for future studies of aging, neurodegenerative disease, and therapeutic intervention in the marmoset model.

animal behavior and cognition↗

bioRxiv2025

Cognitive strategy accounts for failure on a hippocampal relational memory task in non-human primates

Relational memory, the ability to flexibly encode and retrieve associations among distinct elements, is critically dependent on the hippocampus and declines with age in humans. The Transverse Patterning (TP) task is designed to probe relational memory by requiring learning of hierarchical, circular stimulus relationships (e.g., A+ B-, B+ C-, C+ A-), a structure akin to rock-paper-scissors. In humans, TP performance is reliably impaired by hippocampal damage and aging. In non-human primates, however, findings have been inconsistent with some studies demonstrating clear hippocampal dependence, while others report no impairment, or even improvements, following hippocampal lesions. This raises the possibility that species differences in cognitive strategy use may underlie these divergent outcomes. We hypothesized that non-human primates rely on an elemental learning strategy, supported by corticostriatal systems, even when relational memory is required. To test this, we trained young and aged common marmosets (Callithrix jacchus) on the TP task and several control tasks designed to isolate elemental versus configural learning. Marmosets successfully acquired reward contingencies for individual stimulus pairs but failed when success required integrating all three stimulus relationships. In contrast, all animals readily acquired control tasks solvable via simple stimulus-response associations. Notably, there was no evidence of age-related impairment on TP or control task performance. Given the early vulnerability of the hippocampus to aging and the relative preservation of striatal systems, this pattern further supports the conclusion that marmosets rely on a habit-based learning strategy that is poorly suited to relational demands. These findings suggest that humans and non-human primates may approach the same tasks using different cognitive strategies. This has critical implications for interpreting cross-species differences in memory performance and highlights the need to validate which neural systems a task engages in each species before using it as a translational model of hippocampal function or cognitive aging.

animal behavior and cognition↗

bioRxiv2024

The Common Marmoset as a Translational Model for Longitudinal Studies of Cognitive Aging and Individual Vulnerability to Decline

In humans, cognitive aging is highly variable, with some individuals experiencing decline while others remain stable, and different cognitive domains exhibiting uneven vulnerability to aging. The neural mechanisms driving this intra- and inter-individual variability are not fully understood, making longitudinal studies in translational models essential for elucidating the timelines and processes involved. The common marmoset (Callithrix jacchus), a short-lived nonhuman primate, offers an unprecedented opportunity to conduct longitudinal investigations of aging and age-related disease over a condensed time frame, in a highly translatable animal model. The potential of the marmoset as a model for cognitive aging is indisputable, but a comprehensive cognitive battery tailored for longitudinal aging studies has not yet been developed, applied, or validated. This represents a critical missing piece for evaluating the marmoset as a model and understanding the extent to which marmoset cognitive aging mirrors the patterns found in humans, including whether marmosets have individual variability in their vulnerability to age-related cognitive decline. To address this, we developed a comprehensive touchscreen-based neuropsychological test battery for marmosets (MarmoCog), targeting five cognitive domains: working memory, stimulus-reward association learning, cognitive flexibility, motor speed, and motivation. We tested a large cohort of marmosets, ranging from young adults to geriatrics, over several years. We found significant variability in cognitive aging, with the greatest decline occurring in domains dependent on the prefrontal cortex and hippocampus. Additionally, we observed significant inter-individual variability in vulnerability to age-related cognitive decline: some marmosets declined across multiple domains, others in just one, and some showed no decline at all. This pattern mirrors human cognitive aging, solidifies the marmoset as an advantageous model for age-related cognitive decline, and provides a strong foundation for identifying the neural mechanisms involved.

animal behavior and cognition↗

bioRxiv2024

Parallel patterns of cognitive aging in marmosets and macaques

As humans age, some experience cognitive impairment while others do not. When impairment does occur, it is not expressed uniformly across cognitive domains and varies in severity across individuals. Translationally relevant model systems are critical for understanding the neurobiological drivers of this variability, which is essential to uncovering the mechanisms underlying the brains susceptibility to the effects of aging. As such, non-human primates are particularly important due to shared behavioral, neuroanatomical, and age-related neuropathological features with humans. For many decades, macaque monkeys have served as the primary non-human primate model for studying the neurobiology of cognitive aging. More recently, the common marmoset has emerged as an advantageous model for this work due to its short lifespan that facilitates longitudinal studies. Despite their growing popularity as a model, whether marmosets exhibit patterns of age-related cognitive impairment comparable to those observed in macaques and humans remains unexplored. To address this major limitation for the development and evaluation of the marmoset as a model of cognitive aging, we directly compared working memory ability as a function of age in macaques and marmosets on the identical working memory task. Our results demonstrate that marmosets and macaques exhibit remarkably similar age-related working memory deficits, highlighting the value of the marmoset as a model for cognitive aging research within the neuroscience community.

animal behavior and cognition↗

bioRxiv2023

Domain-specific cognitive impairment reflects prefrontal dysfunction in aged common marmosets

Age-related cognitive impairment is not expressed uniformly across cognitive domains. Cognitive functions that rely on brain areas that undergo substantial neuroanatomical changes with age often show age-related impairment, while those that rely on brain areas with minimal age-related change typically do not. The common marmoset has grown in popularity as a model for neuroscience research, but robust cognitive phenotyping, particularly as a function of age and across multiple cognitive domains, is lacking. This presents a major limitation for the development and evaluation of the marmoset as a model of cognitive aging, and leaves open the question of whether they exhibit age-related cognitive impairment that is restricted to some cognitive domains, as in humans. In this study, we characterized stimulus-reward association learning and cognitive flexibility in young adults to geriatric marmosets using a Simple Discrimination and a Serial Reversal task, respectively. We found that aged marmosets show transient impairment in "learning-to-learn" but have conserved ability to form stimulus-reward associations. Furthermore, aged marmosets have impaired cognitive flexibility driven by susceptibility to proactive interference. Since these impairments are in domains critically dependent on the prefrontal cortex, our findings support prefrontal cortical dysfunction as a prominent feature of neurocognitive aging. This work positions the marmoset as a key model for understanding the neural underpinnings of cognitive aging. Significance StatementAging is the greatest risk factor for neurodegenerative disease development, and understanding why is critical for the development of effective therapeutics. The common marmoset, a short-lived non-human primate with neuroanatomical similarity to humans, has gained traction for neuroscientific investigations. However, the lack of robust cognitive phenotyping, particularly as a function of age and across multiple cognitive domains limits their validity as a model for age-related cognitive impairment. We demonstrate that aging marmosets, like humans, have impairment that is specific to cognitive domains reliant on brain areas that undergo substantial neuroanatomical changes with age. This work validates the marmoset as a key model for understanding region-specific vulnerability to the aging process.

neuroscience↗