Strength Of Negative Feedback Research Articles

Matching points of nanolaser based on quantum dot semiconductor laser for positive and negative optoelectronic feedback strength

Matching points of nanolaser based on quantum dot semiconductor laser for positive and negative optoelectronic feedback strength

Changes in hypothalamic–pituitary–adrenal axis function, immunity, and glucose during acute Plasmodium relictum infection in house sparrows (Passer domesticus)

Hosts of the same species vary in physiological responses to the same parasite, and some groups of individuals can disproportionately affect disease dynamics; however, the underlying pathophysiology of host-parasite interactions is poorly understood in wildlife. We tested the hypothesis that the hypothalamic–pituitary–adrenal (HPA) axis mediates host resistance and tolerance to avian malaria during the acute phase of infection by evaluating whether individual variation in circulating glucocorticoids predicted resistance to avian malaria in a songbird. We experimentally inoculated wild-caught house sparrows (Passer domesticus) with naturally sourced Plasmodium relictum and quantified baseline and restraint-induced circulating corticosterone, negative feedback ability, cellular and humoral immune function, and baseline and restraint-induced glycemia, prior to and during acute malaria infection. During peak parasitemia, we also evaluated the expression of several liver cytokines that are established pathological hallmarks of malaria in mammals: two pro-inflammatory (IFN-γ and TNF-α) and two anti-inflammatory (IL-10 and TGF-β). Although most of the host metrics we evaluated were not correlated with host resistance or tolerance to avian malaria, this experiment revealed novel relationships between malarial parasites and the avian immune system that further our understanding of the pathology of malaria infection in birds. Specifically, we found that: (1) TNF-α liver expression was positively correlated with parasitemia; (2) sparrows exhibited an anti-inflammatory profile during malaria infection; and (3) IFN-γ and circulating glucose were associated with several immune parameters, but only in infected sparrows. We also found that, during the acute phase of infection, sparrows increased the strength of corticosterone negative feedback at the level of the pituitary. In the context of our results, we discuss future methodological considerations and aspects of host physiology that may confer resistance to avian malaria, which can help inform conservation and rehabilitation strategies for avifauna at risk.

Endocrine effects of exposure to artificial light at night: A review and synthesis of knowledge gaps

Animals have evolved with natural patterns of light and darkness, such that light serves as an important zeitgeber, allowing adaptive synchronization of behavior and physiology to external conditions. Exposure to artificial light at night (ALAN) interferes with this process, resulting in dysregulation of endocrine systems. In this review, we evaluate the endocrine effects of ALAN exposure in birds and reptiles, identify major knowledge gaps, and highlight areas for future research. There is strong evidence for ecologically relevant levels of ALAN acting as an environmental endocrine disruptor. However, most studies focus on the pineal hormone melatonin, corticosterone release via the hypothalamus-pituitary-adrenal axis, or regulation of reproductive hormones via the hypothalamus-pituitary-gonadal axis, leaving effects on other endocrine systems largely unknown. We call for more research spanning a diversity of hormonal systems and levels of endocrine regulation (e.g. circulating hormone levels, receptor numbers, strength of negative feedback), and investigating involvement of molecular mechanisms, such as clock genes, in hormonal responses. In addition, longer-term studies are needed to elucidate potentially distinct effects arising from chronic exposure. Other important areas for future research effort include investigating intraspecific and interspecific variability in sensitivity to light exposure, further distinguishing between distinct effects of different types of light sources, and assessing impacts of ALAN exposure early in life, when endocrine systems remain sensitive to developmental programming. The effects of ALAN on endocrine systems are likely to have a plethora of downstream effects, with implications for individual fitness, population persistence, and community dynamics, especially within urban and suburban environments.

Frequency response in splicing regulation under mRNA auto-depletion control.

Nowadays, there exists a huge literature about stochastic model of transcriptional and translational control in gene networks. However, results related to post-transcriptional regulation via splicing and its connection with transcriptional and translational regulation are almost missing in the current literature and only related to the steady state moments investigation. Nowadays, it is becoming of paramount importance the need for modeling post-transcriptional regulation via splicing especially for DNA viruses or retroviruses. However, there exists only few studies in the literature about splicing regulation and none of them investigate its behavior in the frequency domain that can unveil important features of dynamical stochastic systems that cannot be revealed by the sole steady state moment investigation. The aim of this work is to theoretically investigate a simple gene network subject to splicing regulation with negative feedback control, implemented through mRNA auto-depletion under a frequency domain perspective. This study showed the pivotal role of the burst size, enhancing the noise power spectrum, as well as the splicing conversion rates capable to increase and decrease the noise power spectrum in the pre-mRNA and mRNA, respectively, for high values of conversion rates. Importantly, it shows the capability of the mRNA autodepletion control to modulate the noise as a frequency-dependent amplifying control as a function of the negative feedback strengths.

Frequency analysis of splicing regulation.

In the past decades, mathematical modelers developed a huge literature to model and analyze gene networks under both deterministic and stochastic formalisms. Such literature is predominantly focused on modeling transcriptional and translational regulation, while the development of proper mathematical frameworks to model and study post-transcriptional regulation via splicing and its connection with transcriptional and translational regulation are almost missing. Nowadays, it is becoming of paramount importance the need for modeling post-transcriptional regulation via splicing especially for bacteria or viruses. However, current literature is focused on investigating splicing regulation at steady state and none of them have the purpose to investigate gene networks behavior in the frequency domain, thus providing only a partial investigation about the system dynamical response. The aim of this work is to theoretically investigate a simple gene network subjects to splicing regulation with/without negative feedback control under a frequency domain perspective. This study showed the pivotal role of the burst size, as well as splicing conversion rates to modulate the noise and the power spectrum response. It also shows an interesting behavior under the frequency domain induced by the merging effect of burst size, splicing conversion rates and negative feedback strength.

Multi-scale modeling of hippo signaling identifies homeostatic control by YAP-LATS negative feedback

The Hippo signaling primarily includes LATS1/2 and YAP1. Recent work has demonstrated a novel negative feedback between YAP1 and LATS1/2. However, how YAP-LATS negative feedback regulates cancer progression remains elusive. We constructed a multi-scale model which integrates angiogenesis, spatiotemporal variation of microenvironmental factors and phenotypic switch of tumor cells. Our simulation replicated the findings that YAP overexpression markedly attenuated cell proliferation owing to elevated negative feedback strength. After disruption of YAP-LATS negative feedback loop, however, YAP overexpression would promote cell proliferation. Consistently, LATS overexpression inhibited cell growth and lowered the proliferation potential. We also employed a putative LATS agonist and identified its dose-dependent tumor suppressive effects. Furthermore, targeted delivery could more effectively inhibit tumor growth. Our model has reconciled experimental findings and implied that reconstruction of functional and/or hyperactivated YAP-LATS negative feedback might be a promising strategy to homeostatic maintenance and tumor suppression.

Dynamical Mechanisms for Gene Regulation Mediated by Two Noncoding RNAs in Long-Term Memory Formation.

Noncoding RNAs such as miRNAs and piRNAs have long-lasting effects on the regulation of gene expression involved in long-term synaptic changes. To characterize gene regulation mediated by small noncoding RNAs associated with long-term memory in Aplysia, we consider two noncoding RNAs stimulated by 5-HT into a gene regulatory network motif model, including miR-124 that binds to and inhibits the mRNA of CREB1 and piR-F that facilitates serotonin-dependent DNA methylation to lead to repression of CREB2. Codimension-1 and -2 bifurcation analyses of 5-HT regulating both miR-124 and piR-F and a negative feedback strength for oscillation reveal rich dynamical properties of bistability and oscillations robust to variations in all other parameters. More importantly, we verify three stimulus protocols of 5-HT in experiments by our model and find that application of five pulses of 5-HT leads to a transient decrease of miR-124 but increase of piR-F concentrations, which matters sustained high level of CREB1 concentration associated with long-term memory. Furthermore, we perform bifurcation analyses for the concentrations of miR-124 and piR-F as two parameters to explore dynamical mechanisms underlying the epigenetic regulation in long-term memory formation. This study provides insights into revealing regulatory roles of epigenetic changes in gene expression involving noncoding RNAs associated with synaptic plasticity.

Soil precipitation legacies influence intraspecific plant–soil feedback

Feedbacks between plants and soil microbial communities can play an important role in structuring plant communities. However, little is known about how soil legacies caused by environmental disturbances such as drought and extreme precipitation events may affect plant-soil feedback or whether plant-soil feedback operates within species as it does between species. If soil legacies alter plant-soil feedback among genotypes within a plant species, then soil legacies may alter the diversity within plant populations. We conducted a fully factorial pairwise plant-soil feedback experiment to test how precipitation legacies influenced intraspecific plant-soil feedbacks among three genotypes of a dominant grass species, Panicum virgatum. Panicum virgatum experienced negative intraspecific plant-soil feedback, i.e., genotypes generally performed worse on soil from the same genotype than different genotypes. Soil precipitation legacies reversed the rank order of the strength of negative feedback among the genotypes. Feedback is often positively correlated with plant relative abundance. Therefore, our results suggest that soil precipitation legacies may alter the genotypic composition of P.virgatum populations, favoring genotypes that develop less negative feedback. Changes in intraspecific diversity will likely further affect community structure and ecosystem functioning, and may constrain the ability of populations to respond to future changes in climate.

Data-driven analysis of a mechanistic model of CAR T cell signaling predicts effects of cell-to-cell heterogeneity

Due to the variability of protein expression, cells of the same population can exhibit different responses to stimuli. It is important to understand this heterogeneity at the individual level, as population averages mask these underlying differences. Using computational modeling, we can interrogate a system much more precisely than by using experiments alone, in order to learn how the expression of each protein affects a biological system. Here, we examine a mechanistic model of CAR T cell signaling, which connects receptor-antigen binding to MAPK activation, to determine intracellular modulations that can increase cellular response. CAR T cell cancer therapy involves removing a patient's T cells, modifying them to express engineered receptors that can bind to tumor-associated antigens to promote tumor cell killing, and then injecting the cells back into the patient. This population of cells, like all cell populations, would have heterogeneous protein expression, which could affect the efficacy of treatment. Thus, it is important to examine the effects of cell-to-cell heterogeneity. We first generated a dataset of simulated cell responses via Monte Carlo simulations of the mechanistic model, where the initial protein concentrations were randomly sampled. We analyzed the dataset using partial least-squares modeling to determine the relationships between protein expression and ERK phosphorylation, the output of the mechanistic model. Using this data-driven analysis, we found that only the expressions of proteins relating directly to the receptor and the MAPK cascade, the beginning and end of the network, respectively, are relevant to the cells’ response. We also found, surprisingly, that increasing the amount of receptor present can actually inhibit the cell's ability to respond due to increasing the strength of negative feedback from phosphatases. Overall, we have combined data-driven and mechanistic modeling to generate detailed insight into CAR T cell signaling.

Single-cell stochastic gene expression kinetics with coupled positive-plus-negative feedback.

Here we investigate single-cell stochastic gene expression kinetics in a minimal coupled gene circuit with positive-plus-negative feedback. A triphasic stochastic bifurcation is observed upon increasing the ratio of the positive and negative feedback strengths, which reveals a strong synergistic interaction between positive and negative feedback loops. We discover that coupled positive-plus-negative feedback amplifies gene expression mean but reduces gene expression noise over a wide range of feedback strengths when promoter switching is relatively slow, stabilizing gene expression around a relatively high level. In addition, we study two types of macroscopic limits of the discrete chemical master equation model: the Kurtz limit applies to proteins with large burst frequencies and the Lévy limit applies to proteins with large burst sizes. We derive the analytic steady-state distributions of the protein abundance in a coupled gene circuit for both the discrete model and its two macroscopic limits, generalizing the results obtained by Liu etal. [Chaos 26, 043108 (2016)CHAOEH1054-150010.1063/1.4947202]. We also obtain the analytic time-dependent protein distribution for the classical Friedman-Cai-Xie random bursting model [Friedman, Cai, and Xie, Phys. Rev. Lett. 97, 168302 (2006)PRLTAO0031-900710.1103/PhysRevLett.97.168302]. Our analytic results are further applied to study the structure of gene expression noise in a coupled gene circuit, and a complete decomposition of noise in terms of five different biophysical origins is provided.

Negative plant-soil feedbacks are stronger in agricultural habitats than in forest fragments in the tropical Andes.

There is now strong evidence suggesting that interactions between plants and their species-specific antagonistic microbes can maintain native plant community diversity. In contrast, the decay in diversity in plant communities invaded by nonnative plant species might be caused by weakening negative feedback strengths, perhaps because of the increased relative importance of plant mutualists such as arbuscular mycorrhizal fungi (AMF). Although the vast majority of studies examining plant-soil feedbacks have been conducted in a single habitat type, there are fewer studies that have tested how the strength and direction of these feedbacks change across habitats with differing dominating plants. In a fragmented montane agricultural system in Colombia, we experimentally teased apart the relative importance of AMF and non-AMF microbes (a microbial filtrate) to the strength and direction of feedbacks in both native and nonnative plant species. We hypothesized that native tree species of forest fragments would exhibit stronger negative feedbacks with a microbial filtrate that likely contained pathogens than with AMF alone, whereas nonnative plant species, especially a highly invasive dominant grass, would exhibit overall weaker negative feedbacks or even positive feedbacks regardless ofthe microbial type. We reciprocally inoculated each of 10 plant species separately with either the AMF community or the microbial filtrate originating from their own conspecifics, or with the AMF or microbial filtrate originating from each of the other nine heterospecific plant species. Overall, we found that the strength of negative feedback mediated by the filtrate was much stronger than feedbacks mediated by AMF. Surprisingly, we found that the two nonnative species, Urochloa brizantha and Coffea arabica, experienced stronger negative feedbacks with microbial filtrate than did the native forest tree species, suggesting that species-specific antagonistic microbes accumulate when a single host species dominates, as is the case in agricultural habitats. However, negative feedback between forest trees and agricultural species suggests that soil community dynamics may contribute to the re-establishment of native species into abandoned agricultural lands. Furthermore, our finding of no negative feedbacks among trees in forest fragments may be due to a loss in diversity of those microbes that drive diversity-maintaining processes in intact tropical forests.

Recovery from repeated stressors: Physiology and behavior are affected on different timescales in house sparrows

For decades, researchers across disciplines have been captivated by classifying, diagnosing, and avoiding the consequences of chronic stress. Despite the vast body of literature this has generated, we still lack the ability to predict which individuals or populations may be susceptible to stress-related pathologies. One critical unanswered question is whether the impacts of repeated stressors are reversible, or if instead they permanently alter an individual. In this study, we exposed house sparrows (Passer domesticus) to 6 days of random, repeated stressors, permitted them 0, 1, 3, or 6 days to recover, and then assessed changes in their body mass, hypothalamic–pituitaryadrenal (HPA) axis (baseline, stress-induced corticosterone, negative feedback strength), immune function, uric acid concentrations, DNA damage levels, and perch hopping activity. Body mass did not vary between groups after recovery. We found that the HPA axis and perch hopping were not significantly impacted by the 6 days of stressors, but that uric acid and DNA damage increased. Short recovery periods tended to negatively affect the HPA axis and reduced uric acid levels, but these were reversed with longer recovery periods. Following the recovery periods, the birds experienced an additional 6 days of random stressors and their responses were assessed again. All recovery times reduced perch hopping and immune function, but paradoxically, DNA damage was highest in the birds that had the longest amount of time to recover. These results show that recovery time affects responses to subsequent chronic stress in complex ways, and highlight the importance of multimodal, interdisciplinary approaches to studying stress physiology.

Stress Resilience and the Dynamic Regulation of Glucocorticoids.

Vertebrates respond to a diversity of stressors by rapidly elevating glucocorticoid (GC) levels. The changes in physiology and behavior triggered by this response can be crucial for surviving a variety of challenges. Yet the same process that is invaluable in coping with immediate threats can also impose substantial damage over time. In addition to the pathological effects of long-term exposure to stress hormones, even relatively brief elevations can impair the expression of a variety of behaviors and physiological processes central to fitness, including sexual behavior, parental behavior, and immune function. Therefore, the ability to rapidly and effectively terminate the short-term response to stress may be fundamental to surviving and reproducing in dynamic environments. Here we review the evidence that variation in the ability to terminate the stress response through negative feedback is an important component of stress coping capacity. We suggest that coping capacity may also be influenced by variation in the dynamic regulation of GCs-specifically, the ability to rapidly turn on and off the stress response. Most tests of the fitness effects of these traits to date have focused on organisms experiencing severe or prolonged stressors. Here we use data collected from a long-term study of tree swallows (Tachycineta bicolor) to test whether variation in negative feedback, or other measures of GC regulation, predict components of fitness in non-chronically stressed populations. We find relatively consistent, but generally weak relationships between different fitness components and the strength of negative feedback. Reproductive success was highest in individuals that both mounted a robust stress response and had strong negative feedback. We did not see consistent evidence of a relationship between negative feedback and adult or nestling survival: negative feedback was retained in the best supported models of nestling and adult survival, but in two of three survival-related analyses the intercept-only model received only slightly less support. Both negative feedback and stress-induced GC levels-but not baseline GCs-were individually repeatable. These measures of GC activity did not consistently covary across ages and life history stages, indicating that they are independently regulated. Overall, the patterns seen here are consistent with the predictions that negative feedback-and the dynamic regulation of GCs-are important components of stress coping capacity, but that the fitness benefits of having strong negative feedback during the reproductive period are likely to manifest primarily in individuals exposed to chronic or repeated stressors.

Strong Dependence of Atmospheric Feedbacks on Mixed-Phase Microphysics and Aerosol-Cloud Interactions in HadGEM3.

We analyze the atmospheric processes that explain the large changes in radiative feedbacks between the two latest climate configurations of the Hadley Centre Global Environmental model. We use a large set of atmosphere‐only climate change simulations (amip and amip‐p4K) to separate the contributions to the differences in feedback parameter from all the atmospheric model developments between the two latest model configurations. We show that the differences are mostly driven by changes in the shortwave cloud radiative feedback in the midlatitudes, mainly over the Southern Ocean. Two new schemes explain most of the differences: the introduction of a new aerosol scheme and the development of a new mixed‐phase cloud scheme. Both schemes reduce the strength of the preexisting shortwave negative cloud feedback in the midlatitudes. The new aerosol scheme dampens a strong aerosol‐cloud interaction, and it also suppresses a negative clear‐sky shortwave feedback. The mixed‐phase scheme increases the amount of cloud liquid water path (LWP) in the present day and reduces the increase in LWP with warming. Both changes contribute to reducing the negative radiative feedback of the increase of LWP in the warmer climate. The mixed‐phase scheme also enhances a strong, preexisting, positive cloud fraction feedback. We assess the realism of the changes by comparing present‐day simulations against observations and discuss avenues that could help constrain the relevant processes.

Recovery periods during repeated stress impact corticosterone and behavioral responses differently in house sparrows

A number of studies have shown that chronic stress can negatively impact both physiology and behavior in a variety of organisms. What has yet to be extensively explored is whether these changes permanently alter an animal's functioning, or if they can be reversed. In this study, we used wild-caught house sparrows (Passer domesticus) to assess how recovery periods influence the physiological and behavioral impacts of an initial four days and subsequent four days of repeated stressors. Birds were randomly assigned to a recovery group and either experienced 0, 24, or 72 h of recovery between the two sets of stressors (cage rolling and cage tapping). We measured the regulation of the hypothalamic pituitary adrenal (HPA) axis by quantifying baseline and stress-induced corticosterone as well as negative feedback strength. We also assessed behavior using neophobia trials to measure how birds altered their approach towards novel objects and their overall activity. Both behavior and corticosterone responses were assessed before the experiment, after the recovery time, and following the final 4 days of stressors. We found that birds that experienced 24 h of recovery had reduced stress-induced corticosterone, but enhanced negative feedback relative to the pre-experiment sample. Additionally, 4 days of stressors was enough to significantly reduce approach latency towards novel objects; however, pre-experiment levels returned with longer periods of recovery. Finally, recovery time did not significantly influence responses to the second 4 days of stressors. Our results indicate that brief recovery periods partially ameliorate the hormonal and behavioral effects of repeated stress.

Stability and Hopf bifurcation analysis in a delayed three-node circuit involving interlinked positive and negative feedback loops

A system involving interlinked positive and negative feedback loops is a flexible motif that can tune itself in gene regulatory networks. It is well known that time delay is inevitable in gene regulatory networks due to transcription and translation not being physically co-located. In this paper, we systematically consider the effect of time delay on the dynamical behavior of the three-node circuit with three time delays. Based on linear stability analysis and bifurcation theory, sufficient conditions for stability of equilibria and oscillatory behaviors via Hopf bifurcation are derived when choosing positive and negative feedback strengths as well as time delays τ1, τ2, τ3 as the bifurcation parameters, respectively. Moreover, stability and direction of the Hopf bifurcation of time delay are studied by using the normal form method and the center manifold theorem. Finally, several examples are performed to illustrate some analytical results we obtained.

Stability and Hopf Bifurcation Analysis in a Delayed Myc/E2F/miR-17-92 Network Involving Interlinked Positive and Negative Feedback Loops

MiR-17-92 plays an important role in regulating the levels of the Myc/E2F protein. In this paper, we consider a coupling network between Myc/E2F/miR-17-92 delayed negative feedback loop and Myc/E2F positive feedback loop described by a two-dimensional delay differential equation. Based on linear stability analysis and bifurcation theory, sufficient conditions for stability of equilibria and oscillatory behaviors via Hopf bifurcation are derived when choosing time delay as well as negative feedback strength associated with oscillations as bifurcation parameters, respectively. Furthermore, direction and stability of Hopf bifurcation of time delay are studied by using the normal form method and center manifold theorem. Finally, several numerical simulations are performed to verify the results we obtained.

House sparrows (Passer domesticus) adjusted hypothalamic-pituitary-adrenal axis negative feedback and perch hopping activities in response to a single repeated stimulus.

Chronic stress has been extensively studied in both laboratory and field settings; however, a conclusive and consistent phenotype has not been reached. Several studies have reported attenuation of the hypothalamic-pituitary-adrenal axis during experiments intended to cause chronic stress. We sought to determine whether this attenuation could be indicative of habituation. Importantly, we were not investigating habituation to a specific stimulus-as many stress physiology studies do-but rather we assessed how the underlying physiology and behavior changed in response to repeated stressor presentation. We exposed house sparrows (Passer domesticus) to a single stimulus twice per day at random times for 8 consecutive days. We predicted that this period of time would be long enough for the birds to determine that these acute stressors were not, in fact, dangerous and they would, therefore, acclimate. A second control group remained undisturbed for the same period of time. We measured baseline, stress-induced, negative feedback strength, and maximum production of corticosterone as well as neophobic behavior before, during, and after this 8-day experiment. When birds experienced a stimulus for 4 days, their negative feedback strength was significantly diminished, but recovered after the second 4 days. Additionally, perch hopping decreased and recovered in this same time frame. These data suggest that distinct physiological and behavioral responses arise when house sparrows are exposed to the same stressor for several consecutive days as opposed to many stressors layered on top of one another. Furthermore, they indicate that habituation-as with chronic stress-can appear differently depending on the metric being examined.

Frequency-dependent feedback constrains plant community coexistence.

Ecological theory suggests that coexistence of many species within communities requires negative frequency-dependent feedbacks to prevent exclusion of the least fit species. For plant communities, empirical evidence of negative frequency dependence driving species coexistence and diversity patterns is rapidly accumulating, but connecting these findings to theory has been difficult as corresponding theoretical frameworks only consider small numbers of species. Here, we show how frequency-dependent feedback constrains community coexistence, regardless of the number of species and inherent fitness inequalities between them. Any interaction network can be characterized by a single community interaction coefficient, IC, which determines whether community-level feedback is positive or negative. Negative feedback is a necessary (but not sufficient) condition for persistence of the entire community. Even in cases where the coexistence equilibrium state cannot recover from perturbations, IC < 0 can enable species persistence via cyclic succession. The number of coexisting species is predicted to increase with the average strength of negative feedback. This prediction is supported by patterns of tree species diversity in more than 200,000 deciduous forest plots in the eastern United States, which can be reproduced in simulations that span the observed range of community feedback. By providing a quantitative metric for the strength of negative feedback needed for coexistence, we can now integrate theory and empirical data to test whether observed feedback-diversity correlations are strong enough to infer causality.

Motivation dynamically increases noise resistance by internal feedback during movement

Motivation improves performance, pushing us beyond our normal limits. One general explanation for this is that the effects of neural noise can be reduced, at a cost. If this were possible, reward would promote investment in resisting noise. But how could the effects of noise be attenuated, and why should this be costly? Negative feedback may be employed to compensate for disturbances in a neural representation. Such feedback would increase the robustness of neural representations to internal signal fluctuations, producing a stable attractor. We propose that encoding this negative feedback in neural signals would incur additional costs proportional to the strength of the feedback signal. We use eye movements to test the hypothesis that motivation by reward improves precision by increasing the strength of internal negative feedback. We find that reward simultaneously increases the amplitude, velocity and endpoint precision of saccades, indicating true improvement in oculomotor performance. Analysis of trajectories demonstrates that variation in the eye position during the course of saccades is predictive of the variation of endpoints, but this relation is reduced by reward. This indicates that motivation permits more aggressive correction of errors during the saccade, so that they no longer affect the endpoint. We suggest that such increases in internal negative feedback allow attractor stability, albeit at a cost, and therefore may explain how motivation improves cognitive as well as motor precision.