Biology subjects

Holmes, C. D.

Publications and source records attributed to Holmes, C. D..

3 recordsLinked to original sources

bioRxiv2026

Reaction-time asymmetry covaries with shifts in hand choice in macaques

How primates choose which hand to reach with remains poorly understood. Humans prefer the hand on the target's side of the body midline, and that preference shifts with biomechanical cost and with head and gaze direction. Earlier monkey studies used only two targets, one per side, too few to fit a psychometric function. Reaction time may also reflect the choice; in humans it is longest at the point of subjective equality (PSE), the target position at which either hand is equally likely to be chosen. We measured hand choice at ten horizontal target positions in two male rhesus macaques (Macaca mulatta) that chose freely on each trial. For peripheral targets, both animals used the hand on the same side of the body midline, with a well-defined transition in between. Displacing the hands, rotating the head, or displacing gaze to one side each moved the PSE toward that side. Reaction time was longest near the PSE. Hand displacement slowed the hand on the displaced side, and gaze displacement slowed the hand opposite the gaze. In every condition, the farther the PSE lay toward one side, the slower that side's hand was relative to the other. Macaque hand choice thus resembles human hand choice, making the macaque a tractable model for studying how the brain chooses a hand.

neuroscience↗

bioRxiv2025

AquIRE reveals multiple mechanisms of clinically induced RNA damage and the conservation and dynamics of glycoRNAs

RNA is subject to many modifications, from small chemical changes such as methylation through to conjugation of biomolecules such as glycans. As well as these endogenously written modifications, RNA is also exposed to damage induced by its environment. Certain clinical compounds are known to drive covalent modifications of RNA with a growing appreciation for how these affect function. To understand the regulation of these modifications we need a reliable, sensitive and rapid methodology for their quantification. Thus, we developed AquIRE and applied it to the analysis of drug-induced RNA damage, showing this to be widespread with intricate temporal dynamics. Using the same methodology we identify RNA:protein crosslinking and the rewriting of the epitranscriptome as a consequence of clinical RNA damage. We also demonstrate how liquid-liquid phase separation increases RNA damage and expand the horizons of the glycoRNA world across the kingdoms of life and into cell-free glycoRNA.

molecular biology↗

bioRxiv2025

Compositional architecture: Orthogonal neural codes for task context and spatial memory in prefrontal cortex

The prefrontal cortex (PFC) is crucial for maintaining working memory across diverse cognitive tasks, yet how it adapts to varying task demands remains unclear. Compositional theories propose that cognitive processes in neural network rely on shared components that can be reused to support different behaviors. However, previous studies have suggested that working memory components are task specific, challenging this framework. Here, we revisit this question using a population-based approach. We recorded neural activity in macaque monkeys performing two spatial working memory tasks with opposing goals: one requiring movement toward previously presented spatial locations (look task) and the other requiring avoidance of those locations (no-look task). Despite differences in task demands, we found that spatial memory representations were largely conserved at the population level, with a common low-dimensional neural subspace encoding memory across both tasks. In parallel, task identity was encoded in an orthogonal subspace, providing a stable and independent representation of contextual information. These results provide neural evidence for a compositional model of working memory, where representational geometry enables the efficient and flexible reuse of mnemonic codes across behavioral contexts while maintaining an independent representation of context.

neuroscience↗