Cortical quantity representations of visual numerosity and timing overlap increasingly into superior cortices but remain distinct.

Many sensory brain areas are organized as topographic maps where neural response preferences change gradually across the cortical surface. Within association cortices, 7-Tesla fMRI and neural model-based analyses have also revealed many topographic maps for quantities like numerosity and event timing, often in similar locations. Numerical and temporal quantity estimations also show behavioral similarities and even interactions. For example, the duration of high-numerosity displays is perceived as longer than that of low-numerosity displays. Such interactions are often ascribed to a generalized magnitude system with shared neural responses across quantities. Anterior quantity responses are more closely linked to behavior. Here, we investigate whether common quantity representations hierarchically emerge by asking whether numerosity and timing maps become increasingly closely related in their overlap, response preferences, and topography. While the earliest quantity maps do not overlap, more superior maps overlap increasingly. In these overlapping areas, some intraparietal maps have consistently correlated numerosity and timing preferences, and some maps have consistent angles between the topographic progressions of numerosity and timing preferences. However, neither of these relationships increases hierarchically like the amount of overlap does. Therefore, responses to different quantities are initially derived separately, then progressively brought together, without generally becoming a common representation. Bringing together distinct responses to different quantities may underlie behavioral interactions and allow shared access to comparison and action planning systems.

First-passage time approach to controlling noise in the timing of intracellular events.

In the noisy cellular environment, gene products are subject to inherent random fluctuations in copy numbers over time. How cells ensure precision in the timing of key intracellular events despite such stochasticity is an intriguing fundamental problem. We formulate event timing as a first-passage time problem, where an event is triggered when the level of a protein crosses a critical threshold for the first time. Analytical calculations are performed for the first-passage time distribution in stochastic models of gene expression. Derivation of these formulas motivates an interesting question: Is there an optimal feedback strategy to regulate the synthesis of a protein to ensure that an event will occur at a precise time, while minimizing deviations or noise about the mean? Counterintuitively, results show that for a stable long-lived protein, the optimal strategy is to express the protein at a constant rate without any feedback regulation, and any form of feedback (positive, negative, or any combination of them) will always amplify noise in event timing. In contrast, a positive feedback mechanism provides the highest precision in timing for an unstable protein. These theoretical results explain recent experimental observations of single-cell lysis times in bacteriophage [Formula: see text] Here, lysis of an infected bacterial cell is orchestrated by the expression and accumulation of a stable [Formula: see text] protein up to a threshold, and precision in timing is achieved via feedforward rather than feedback control. Our results have broad implications for diverse cellular processes that rely on precise temporal triggering of events.

Libet's experiment: A complex replication.

Libet's experiment is an influential classical study, which does not stop provoking heated debates. However, a full-scale replication has not been carried out to this day. Libet-style studies have usually focused on isolated ideas and concepts and never on the whole experiment in all its complexity. This paper presents detailed methodological description and results of a complex replication study. The methodology follows Libet's directions closely in most cases; when it does not, the differences are described and elaborated. The results replicate Libet's key findings, but substantial differences were found in some of the results' categories, such as the introspective reports or the number of readiness-potentials found. The discussion also addresses some current problems pertaining the methodology of the Libet-style experiments and provides some recommendations based on a detailed process evaluation.

Association between cardiac time intervals and incident heart failure after acute coronary syndrome.

BACKGROUND: Cardiac time intervals are sensitive markers of myocardial dysfunction that predispose to heart failure (HF). We aimed to investigate the association between cardiac time intervals and HF in patients with acute coronary syndrome (ACS). METHODS: This study included 386 ACS patients treated with percutaneous coronary intervention (PCI). Patients underwent an echocardiography examination a median of two days after PCI. Cardiac time intervals including isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), and systolic ejection time (ET), and myocardial performance index (MPI) were obtained by tissue Doppler echocardiography. The outcome was incident HF. RESULTS: During follow-up (median 4.3, IQR:1.0-6.7 years), 140 (36%) developed HF. In unadjusted analyses, IVRT was not associated with HF (HR 1.02 (0.95-1.10), p = 0.61, per 10ms increase), and neither was IVCT (HR 0.07 (0.95-1.22), p = 0.26, per 10ms increase). Increasing MPI was associated with a higher risk of HF (HR 1.20 (1.08-1.34), P = 0.001, per 0.1 increase), and so was decreasing ET (HR 1.13 (1.07-1.18), P < 0.001 per 10ms decrease). After multivariable adjustment for cardiovascular risk factors, MPI (HR 1.13 (1.01-1.27), P = 0.034) and ET (HR 1.09 (1.01-1.17), P = 0.025) remained significantly associated with incident HF. LVEF modified the association between ET and HF (p for interaction = 0.002), such that ET was associated with HF in patients with LVEF ≥ 36% (HR = 1.15 (1.06-1.24), P = 0.001, per 10ms decrease). CONCLUSION: In patients admitted with ACS, shortened ET and higher MPI were independently associated with an increased risk of incident HF. Additionally, ET was associated with incident HF in patients with LVEF above 36%.

Parent--offspring similarity in the timing of developmental events: an origin of heterochrony?

Understanding the link between ontogeny (development) and phylogeny (evolution) remains a key aim of biology. Heterochrony, the altered timing of developmental events between ancestors and descendants, could be such a link although the processes responsible for producing heterochrony, widely viewed as an interspecific phenomenon, are still unclear. However, intraspecific variation in developmental event timing, if heritable, could provide the raw material from which heterochronies originate. To date, however, heritable developmental event timing has not been demonstrated, although recent work did suggest a genetic basis for intraspecific differences in event timing in the embryonic development of the pond snail, Radix balthica. Consequently, here we used high-resolution (temporal and spatial) imaging of the entire embryonic development of R. balthica to perform a parent-offspring comparison of the timing of twelve, physiological and morphological developmental events. Between-parent differences in the timing of all events were good predictors of such timing differences between their offspring, and heritability was demonstrated for two of these events (foot attachment and crawling). Such heritable intraspecific variation in developmental event timing could be the raw material for speciation events, providing a fundamental link between ontogeny and phylogeny, via heterochrony.

Impact of echocardiographic analyses of valvular event timing on myocardial work indices.

AIMS: Valvular event timing is an integral part of echocardiographic pressure-strain loop (PSL) analyses. The impact that different event timing modalities may have on myocardial work indices is unknown. METHODS AND RESULTS: A methodological study was performed on 200 subjects, including 50 healthy subjects, 50 with aortic valve sclerosis, 50 with atrial fibrillation, and 50 with reduced left ventricular ejection fraction. Valvular event timing was estimated by visual assessment, spectral Doppler, and colour tissue Doppler imaging (TDI) M-mode. These valvular event timings were added to the same PSL analyses sequentially to acquire myocardial work indices, including global work index (GWI). For the 200 participants, the median age was 72 years, 50% were men, and mean blood pressure was 143/80 mmHg. Valvular event timings differed between all three modalities and so did all myocardial work indices. Compared with visual assessment, spectral Doppler resulted in a significantly higher GWI (mean difference: 114 ± 93 mmHg%, P < 0.001), and so did TDI (mean difference: 83 ± 90 mmHg%, P < 0.001). A higher GWI by spectral Doppler than by TDI was also observed (mean difference: 30 ± 53 mmHg%, P < 0.001). In the healthy subgroup, a systematic bias was observed for spectral Doppler compared with visual assessment (mean difference: 160 ± 77 mmHg%, P < 0.001), and a similar trend was noted for TDI vs. visual assessment (mean difference: 124 ± 74 mmHg%, P < 0.001). CONCLUSION: Myocardial work indices differ depending on the event timing modality used, with visual assessment yielding lower GWI values compared with Doppler-based methods. Serial PSL analyses should apply the same event timing method.

An Optimal Lysis Time Maximizes Bacteriophage Fitness in Quasi-Continuous Culture.

Optimality models have a checkered history in evolutionary biology. While optimality models have been successful in providing valuable insight into the evolution of a wide variety of biological traits, a common objection is that optimality models are overly simplistic and ignore organismal genetics. We revisit evolutionary optimization in the context of a major bacteriophage life history trait, lysis time. Lysis time refers to the period spanning phage infection of a host cell and its lysis, whereupon phage progenies are released. Lysis time, therefore, directly determines phage fecundity assuming progeny assembly does not exhaust host resources prior to lysis. Noting that previous tests of lysis time optimality rely on batch culture, we implemented a quasi-continuous culture system to observe productivity of a panel of isogenic phage λ genotypes differing in lysis time. We report that under our experimental conditions, λ phage productivity is maximized around optimal lysis times ranging from 60 to 100 min, and λ wildtype strain falls within this range. It would appear that natural selection on phage λ lysis time uncovered a set of genetic solutions that optimized progeny production in its ecological milieu relative to alternative genotypes. We discuss this finding in light of recent results that lysis time variation is also minimized in the strains with lysis times closer to the λ wild-type strain. IMPORTANCE Optimality theory presents the idea that natural selection acts on organismal traits to produce genotypes that maximize organismal survival and reproduction. As such, optimality theory is a valuable tool in guiding our understanding of the genetic constraints and tradeoffs organisms experience as their genotypes are selected to produce optimal solutions to biological problems. However, optimality theory is often critiqued as being overly simplistic and ignoring the roles of chance and history in the evolution of organismal traits. We show here that the wild-type genotype of a popular laboratory model organism, the bacteriophage λ, produces a phenotype for a major life history trait, lysis time, that maximizes the reproductive success of bearers of that genotype relative to other possible genotypes. This result demonstrates, as is rarely shown experimentally, that natural selection can achieve optimal solutions to ecological challenges.

Experience with Event Timing Does not Alter Emergent Timing: Further Evidence for Robustness of Event and Emergent Timing.

Although, event and emergent timings are thought of as mutually exclusive, significant correlations between tapping and circle drawing (Baer, Thibodeau, Gralnick, Li, & Penhune, 2013 ; Studenka, Zelaznik, & Balasubramaniam, 2012 ; Zelaznik & Rosenbaum, 2010 ) suggest that emergent timing may not be as robust as once thought. We aimed to test this hypothesis in both a younger (18-25) and older (55-100) population. Participants performed one block of circle drawing as a baseline, then six blocks of tapping, followed by circle drawing. We examined the use of event timing. Our hypothesis that acute experience with event timing would bias an individual to use event timing during an emergent task was not supported. We, instead, support the robustness of event and emergent timing as independent timing modes.

The role of multiple internal timekeepers and sources of feedback on interval timing.

The aim of this experiment was to document the role of multiple internal clock mechanisms and external sources of temporal feedback on reducing timing variability when two fingers tap instead of one (a phenomenon known as the bimanual advantage). Previous research documents a reduction in timed interval variability when two effectors time instead of one. In addition, interval variability decreases with multiple sources of feedback. To date, however, no research has explored the separate roles of feedback and internal timing on the bimanual advantage. We evaluated the bimanual advantage in a task that does not utilise an internal clock (circle drawing). Participants performed both unimanual and bimanual timing while tapping or drawing circles. Both tasks were performed with and without tactile feedback at the timing goal. We document reduced bimanual timing variability only for tasks that utilise internal clock-like timing (tapping). We also document reduced timing variability for timing with greater sensory feedback (tactile vs no-tactile feedback tapping). We conclude that internal clock mechanisms are necessary for bimanual advantage to occur, but that multiple sources of feedback can also serve to improve internal timing, which ties together current theories of bimanual advantage.

Nuclear event zero time determination using analytical solutions of radioxenon activities under in-growth condition.

Motivated by simplifying the calculation process of radioxenon isotopic activity used by scientist community in nuclear event characterization, the analytical formulas of the numbers of nuclides and isotopic activities of CTBT relevant radioxenon Xe-135, Xe-133m, Xe-133 and Xe-131m proposed in this work can be useful and incorporated in the calculation algorithms for nuclear event studies. The calculated ages using analytical formulas and radioxenon activity data from real observations compare well with the reported ages and show good results of event timing precision.

A summary of the BARREL campaigns: Technique for studying electron precipitation.

BARREL observed electron precipitation over wide range of energy and timescalesPrecipitating electron distribution is determined using spectroscopy for 19 January 2013 eventBARREL timing data has accuracy within sampling interval of 0.05 s.

Timing skills and expertise: discrete and continuous timed movements among musicians and athletes.

INTRODUCTION: Movement-based expertise relies on precise timing of movements and the capacity to predict the timing of events. Music performance involves discrete rhythmic actions that adhere to regular cycles of timed events, whereas many sports involve continuous movements that are not timed in a cyclical manner. It has been proposed that the precision of discrete movements relies on event timing (clock mechanism), whereas continuous movements are controlled by emergent timing. We examined whether movement-based expertise influences the timing mode adopted to maintain precise rhythmic actions. MATERIALS AND METHOD: Timing precision was evaluated in musicians, athletes and control participants. Discrete and continuous movements were assessed using finger-tapping and circle-drawing tasks, respectively, based on the synchronization-continuation paradigm. In Experiment 1, no auditory feedback was provided in the continuation phase of the trials, whereas in Experiment 2 every action triggered a feedback tone. RESULTS: Analysis of precision in the continuation phase indicated that athletes performed significantly better than musicians and controls in the circle-drawing task, whereas musicians were more precise than controls in the finger tapping task. Interestingly, musicians were also more precise than controls in the circle-drawing task. RESULTS also showed that the timing mode adopted was dependent on expertise and the presence of auditory feedback. DISCUSSION: RESULTS showed that movement-based expertise is associated with enhanced timing, but these effects depend on the nature of the training. Expertise was found to influence the timing strategy adopted to maintain precise rhythmic movements, suggesting that event and emergent timing mechanisms are not strictly tied to specific tasks, but can both be adopted to achieve precise timing.