Biology subjects

Stark, C. E.

Publications and source records attributed to Stark, C. E..

6 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

Lower GABA levels in the posterior cingulate are linked with poorer episodic memory in healthy older adults

Age-related deficits in episodic memory and mnemonic discrimination are associated with an increased risk of neurodegenerative diseases, such as Alzheimers disease (AD) (Stark et al., 2013). While much research has focused on hippocampal contributions to these age-related changes (Stark et al., 2019), less is known about the role of posterior cingulate cortex (PCC) especially reduced inhibition in episodic memory deficit. PCC has connections to the medial temporal lobe and is linked to memory declines (Greicius et al., 2004). It is also one of the most vulnerable regions to amyloid deposition in AD (Yokoi et al., 2018). This study hypothesized and found that age-related declines in GABAergic function (brains major inhibitory neurotransmitter) within the PCC contributes to individual differences in memory performance in healthy older adults. Using Magnetic Resonance Spectroscopy, we measured GABA levels in the PCC in 22 healthy younger and 30 older adults. We assessed episodic memory using Rey Delayed Auditory Verbal Learning Test (RAVLT) and Mnemonic Similarity Task (MST). We found that both raw GABA levels and episodic memory performance are lower in older adults compared to young. This reduction in GABA levels is subserved by age-related changes in tissue-composition as evidenced by no age-group differences in corrected GABA levels. More importantly, lower GABA levels (independent of tissue-correction) were associated with poorer episodic performance including delayed recall and mnemonic discrimination. This research suggests that therapeutically targeting posterior cingulate GABA levels might help slow or alleviate memory decline. Significance StatementThis study provides novel insights into the role of posterior cingulate cortex (PCC) GABA+ levels in age-related memory deficits. Our findings demonstrate that lower PCC GABA+ levels in older adults are associated with poorer performance on episodic memory tasks, particularly those involving mnemonic discrimination and word-list learning. This research expands on the growing body of literature linking GABAergic dysfunction to age-related cognitive impairments and suggests that GABAergic changes in the PCC contribute to episodic memory deficits. Importantly, our results highlight the potential of targeting PCC GABA levels as a therapeutic strategy to slow or mitigate memory decline in aging. These findings also offer promising avenues for future research into early biomarkers for Alzheimers disease and other neurodegenerative conditions.

neuroscience↗

bioRxiv2023

In vivo proton MR Spectroscopy of the healthy and diseased human brain

Proton (1H) Magnetic Resonance Spectroscopy (MRS) is a non-invasive tool capable of quantifying brain metabolite concentrations in vivo. Prioritization of standardization and accessibility in the field has led to the development of universal pulse sequences, methodological consensus recommendations, and the development of open-source analysis software packages. One on-going challenge is methodological validation with ground-truth data. As ground-truths are rarely available for in vivo measurements, data simulations have become an important tool. The diverse literature of metabolite measurements has made it challenging to define ranges to be used within simulations. Especially for the development of deep learning and machine learning algorithms, simulations must be able to produce accurate spectra capturing all the nuances of in vivo data. Therefore, we sought to determine the physiological ranges and relaxation rates of brain metabolites which can be used both in data simulations and as reference estimates. Using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, weve identified relevant MRS research articles and created an open-source database containing methods, results, and other article information as a resource. Using this database, expectation values and ranges for metabolite concentrations and T2 relaxation times are established based upon a meta-analyses of healthy and diseased brains.

neuroscience↗

bioRxiv2019

Enriching hippocampal memory function in older adults through video games

Healthy aging is accompanied by a steady cognitive decline with clear losses in memory. Animal studies have consistently demonstrated that simply modifying an animals living environment (known as environmental enrichment) can have a positive influence on age-related cognitive decline in the hippocampus. Previously, we showed that playing immersive 3D video games can improve hippocampal-based memory in young healthy adults, suggesting that the exploration of the large open worlds of modern-day video games may act as proxy for environmental enrichment in humans. Here, we replicated our previous video game study in older adults and showing that playing video games for 4 weeks can improve hippocampal-based memory in a population that is already experiencing age-related decline in this memory. Furthermore, we showed that the improvements last for up to 4 weeks past the intervention, highlighting the potential of video games as intervention for age-related cognitive decline.

neuroscience↗

bioRxiv2019

Enriching hippocampal memory function in older adults through real-world exploration

Age-related structural and functional changes in the hippocampus can have a severe impact on hippocampally-dependent memory performance. Here we test the hypothesis that a real-world spatial exploration intervention will improve hippocampally-dependent memory performance in healthy older adults. We found that following our intervention, participants lure discrimination index (LDI) was significantly higher than it was at baseline, while traditional recognition scores remained relatively unchanged. These results point to the viability of a spatial exploration intervention for improving hippocampally-dependent memory in older adults.

neuroscience↗

bioRxiv2019

Age-related alterations in functional connectivity along the longitudinal axis of the hippocampus and its subfields

Aging causes hippocampal circuit alterations that differentially affect hippocampal subfields and are associated with age-related memory decline. Additionally, functional organization along the longitudinal axis of the hippocampus has revealed distinctions between anterior and posterior (A-P) connectivity. Here, we examined the functional connectivity (FC) differences between young and older adults at high-resolution within the medial temporal lobe network (entorhinal, perirhinal, and parahippocampal cortices), allowing us to explore how hippocampal subfield connectivity across the longitudinal axis of the hippocampus changes with age. Overall, we found reliably greater connectivity for younger adults than older adults between the hippocampus and PHC and PRC. This drop in functional connectivity was more pronounced in the anterior regions of the hippocampus than the posterior ones, consistent for each of the hippocampal subfields. Further, intra-hippocampal connectivity also reflected an age-related decrease in functional connectivity within the anterior hippocampus in older adults that was offset by an increase in posterior hippocampal functional connectivity. Interestingly, the anterior-posterior shift in older adults between hippocampus and PHC was predictive of lure discrimination performance on the MST, suggesting that this shift may reflect a compensation mechanism that preserves memory performance. While age-related dysfunction within the hippocampal subfields has been well-documented, these results suggest that the age-related A-P shift in hippocampal connectivity may also contribute significantly to memory decline in older adults.

neuroscience↗