Quantitatively assessing aging effects in rapid motor behaviours: a cross-sectional study.

BACKGROUND: An individual's rapid motor skills allow them to perform many daily activities and are a hallmark of physical health. Although age and sex are both known to affect motor performance, standardized methods for assessing their impact on upper limb function are limited. METHODS: Here we perform a cross-sectional study of 643 healthy human participants in two interactive motor tasks developed to quantify sensorimotor abilities, Object-Hit (OH) and Object-Hit-and-Avoid (OHA). The tasks required participants to hit virtual objects with and without the presence of distractor objects. Velocities and positions of hands and objects were recorded by a robotic exoskeleton, allowing a variety of parameters to be calculated for each trial. We verified that these tasks are viable for measuring performance in healthy humans and we examined whether any of our recorded parameters were related to age or sex. RESULTS: Our analysis shows that both OH and OHA can assess rapid motor behaviours in healthy human participants. It also shows that while some parameters in these tasks decline with age, those most associated with the motor system do not. Three parameters show significant sex-related effects in OH, but these effects disappear in OHA. CONCLUSIONS: This study suggests that the underlying effect of aging on rapid motor behaviours is not on the capabilities of the motor system, but on the brain's capacity for processing inputs into motor actions. Additionally, this study provides a baseline description of healthy human performance in OH and OHA when using these tasks to investigate age-related declines in sensorimotor ability.

Capacity Limits Lead to Information Bottlenecks in Ongoing Rapid Motor Behaviors.

Studies of ongoing, rapid motor behaviors have often focused on the decision-making implicit in the task. Here, we instead study how decision-making integrates with the perceptual and motor systems and propose a framework of limited-capacity, pipelined processing with flexible resources to understand rapid motor behaviors. Results from three experiments show that human performance is consistent with our framework: participants perform objectively worse as task difficulty increases, and, surprisingly, this drop in performance is largest for the most skilled performers. As well, our analysis shows that the worst-performing participants can perform equally well under increased task demands, which is consistent with flexible neural resources being allocated to reduce bottleneck effects and improve overall performance. We conclude that capacity limits lead to information bottlenecks and that processes like attention help reduce the effects that these bottlenecks have on maximal performance.

Petri net siphon analysis and graph theoretic measures for identifying combination therapies in cancer.

Epidermal Growth Factor Receptor (EGFR) signaling to the Ras-MAPK pathway is implicated in the development and progression of cancer and is a major focus of targeted combination therapies. Physiochemical models have been used for identifying and testing the signal-inhibiting potential of targeted therapies, however, their application to larger multi-pathway networks is limited by the availability of experimentally-determined rate and concentration parameters. An alternate strategy for identifying and evaluating drug-targetable nodes is proposed. A physiochemical model of EGFR-Ras-MAPK signaling is implemented and calibrated to experimental data. Essential topological features of the model are converted into a Petri net and nodes that behave as siphons-a structural property of Petri nets-are identified. Siphons represent potential drug-targets since they are unrecoverable if their values fall below a threshold. Centrality measures are then used to prioritize siphons identified as candidate drug-targets. Single and multiple drug-target combinations are identified which correspond to clinically relevant drug targets and exhibit inhibition synergy in physiochemical simulations of EGF-induced EGFR-Ras-MAPK signaling. Taken together, these studies suggest that siphons and centrality analyses are a promising computational strategy to identify and rank drug-targetable nodes in larger networks as they do not require knowledge of the dynamics of the system, but rely solely on topology.