Optimal anticipatory control as a theory of motor preparation

Supported by a decade of primate electrophysiological experiments, the prevailing theory of neural motor control holds that movement generation is accomplished by a preparatory process that progressively steers the state of the motor cortex into a movement-specific optimal subspace prior to movement onset. The state of the cortex then evolves from these optimal subspaces, producing patterns of neural activity that serve as control inputs to the musculature. This theory, however, does not address the following questions: what characterizes the optimal subspace and what are the neural mechanisms that underlie the preparatory process? We address these questions with a circuit model of movement preparation and control. Specifically, we propose that preparation can be achieved by optimal feedback control (OFC) of the cortical state via a thalamo-cortical loop. Under OFC, the state of the cortex is selectively controlled along state-space directions that have future motor consequences, and not in other inconsequential ones. We show that OFC enables fast movement preparation and explains the observed orthogonality between preparatory and movement-related monkey motor cortex activity. This illustrates the importance of constraining new theories of neural function with experimental data. However, as recording technologies continue to improve, a key challenge is to extract meaningful insights from increasingly large-scale neural recordings. Latent variable models (LVMs) are powerful tools for addressing this challenge due to their ability to identify the low-dimensional latent variables that best explain these large data sets. One shortcoming of most LVMs, however, is that they assume a Euclidean latent space, while many kinematic variables, such as head rotations and the configuration of an arm, are naturally described by variables that live on non-Euclidean latent spaces (e.g., SO(3) and tori). To address this shortcoming, we propose the Manifold Gaussian Process Latent Variable Model, a method for simultaneously inferring nonparametric tuning curves and latent variables on non-Euclidean latent spaces. We show that our method is able to correctly infer the latent ring topology of the fly and mouse head direction circuits.This work was supported by a Trinity-Henry Barlow scholarship and a scholarship from the Ministry of Education, ROC Taiwan

OwlDE:Making ODEs first-class Owl citizens

Source code of [OwlDE](https://github.com/owlbarn/owl_ode), a suite of ordinary differential equation integrators for [Owl](https://github.com/owlbarn/owl), the OCaml scientific framework

Null Ain't Dull: New Perspectives on Motor Cortex.

Classical work has viewed primary motor cortex (M1) as a controller of muscle and body dynamics. A recent brain-computer interface (BCI) experiment suggests a new, complementary perspective: M1 is itself a dynamical system under active control of other circuits

Neuroscience out of control: control-theoretic perspectives on neural circuit dynamics.

A major challenge in systems neuroscience is to understand how the dynamics of neural circuits give rise to behaviour. Analysis of complex dynamical systems is also at the heart of control engineering, where it is central to the design of robust control strategies. Although a rich engineering literature has grown over decades to facilitate the analysis of such systems, little of it has percolated into neuroscience so far. Here, we give a brief introduction to a number of core control-theoretic concepts that provide useful perspectives on neural circuit dynamics. We introduce important mathematical tools related to these concepts, and establish connections to neural circuit analysis, focusing on a number of themes that have arisen from the modern 'state-space' view on neural population dynamics

Minimum Description Length Control

We propose a novel framework for multitask reinforcement learning based on the minimum description length (MDL) principle. In this approach, which we term MDL-control (MDL-C), the agent learns the common structure among the tasks with which it is faced and then distills it into a simpler representation which facilitates faster convergence and generalization to new tasks. In doing so, MDL-C naturally balances adaptation to each task with epistemic uncertainty about the task distribution. We motivate MDL-C via formal connections between the MDL principle and Bayesian inference, derive theoretical performance guarantees, and demonstrate MDL-C's empirical effectiveness on both discrete and high-dimensional continuous control tasks

Emerged HA and NA Mutants of the Pandemic Influenza H1N1 Viruses with Increasing Epidemiological Significance in Taipei and Kaohsiung, Taiwan, 2009–10

The 2009 influenza pandemic provided an opportunity to observe dynamic changes of the hemagglutinin (HA) and neuraminidase (NA) of pH1N1 strains that spread in two metropolitan areas -Taipei and Kaohsiung. We observed cumulative increases of amino acid substitutions of both HA and NA that were higher in the post–peak than in the pre-peak period of the epidemic. About 14.94% and 3.44% of 174 isolates had one and two amino acids changes, respective, in the four antigenic sites. One unique adaptive mutation of HA2 (E374K) was first detected three weeks before the epidemic peak. This mutation evolved through the epidemic, and finally emerged as the major circulated strain, with significantly higher frequency in the post-peak period than in the pre-peak (64.65% vs 9.28%, p<0.0001). E374K persisted until ten months post-nationwide vaccination without further antigenic changes (e.g. prior to the highest selective pressure). In public health measures, the epidemic peaked at seven weeks after oseltamivir treatment was initiated. The emerging E374K mutants spread before the first peak of school class suspension, extended their survival in high-density population areas before vaccination, dominated in the second wave of class suspension, and were fixed as herd immunity developed. The tempo-spatial spreading of E374K mutants was more concentrated during the post–peak (p = 0.000004) in seven districts with higher spatial clusters (p<0.001). This is the first study examining viral changes during the naïve phase of a pandemic of influenza through integrated virological/serological/clinical surveillance, tempo-spatial analysis, and intervention policies. The vaccination increased the percentage of E374K mutants (22.86% vs 72.34%, p<0.001) and significantly elevated the frequency of mutations in Sa antigenic site (2.36% vs 23.40%, p<0.001). Future pre-vaccination public health efforts should monitor amino acids of HA and NA of pandemic influenza viruses isolated at exponential and peak phases in areas with high cluster cases

Lumican Expression in Diaphragm Induced by Mechanical Ventilation

Diaphragmatic dysfunction found in the patients with acute lung injury required prolonged mechanical ventilation. Mechanical ventilation can induce production of inflammatory cytokines and excess deposition of extracellular matrix proteins via up-regulation of transforming growth factor (TGF)-β1. Lumican is known to participate in TGF-β1 signaling during wound healing. The mechanisms regulating interactions between mechanical ventilation and diaphragmatic injury are unclear. We hypothesized that diaphragmatic damage by short duration of mechanical stretch caused up-regulation of lumican that modulated TGF-β1 signaling.Male C57BL/6 mice, either wild-type or lumican-null, aged 3 months, weighing between 25 and 30 g, were exposed to normal tidal volume (10 ml/kg) or high tidal volume (30 ml/kg) mechanical ventilation with room air for 2 to 8 hours. Nonventilated mice served as control groups.High tidal volume mechanical ventilation induced interfibrillar disassembly of diaphragmatic collagen fiber, lumican activation, type I and III procollagen, fibronectin, and α-smooth muscle actin (α-SMA) mRNA, production of free radical and TGF-β1 protein, and positive staining of lumican in diaphragmatic fiber. Mechanical ventilation of lumican deficient mice attenuated diaphragmatic injury, type I and III procollagen, fibronectin, and α-SMA mRNA, and production of free radical and TGF-β1 protein. No significant diaphragmatic injury was found in mice subjected to normal tidal volume mechanical ventilation.Our data showed that high tidal volume mechanical ventilation induced TGF-β1 production, TGF-β1-inducible genes, e.g., collagen, and diaphragmatic dysfunction through activation of the lumican

Consumer satisfaction with primary care provider choice and associated trust

BACKGROUND: Development of managed care, characterized by limited provider choice, is believed to undermine trust. Provider choice has been identified as strongly associated with physician trust. Stakeholders in a competitive healthcare market have competing agendas related to choice. The purpose of this study is to analyze variables associated with consumer's satisfaction that they have enough choice when selecting their primary care provider (PCP), and to analyze the importance of these variables on provider trust. METHODS: A 1999 randomized national cross-sectional telephone survey conducted of United States residential households, who had a telephone, had seen a medical professional at least twice in the past two years, and aged ≥ 20 years was selected for secondary data analyses. Among 1,117 households interviewed, 564 were selected as the final sample. Subjects responded to a core set of questions related to provider trust, and a subset of questions related to trust in the insurer. A previously developed conceptual framework was adopted. Linear and logistic regressions were performed based on this framework. RESULTS: Results affirmed 'satisfaction with amount of PCP choice' was significantly (p < .001) associated with provider trust. 'PCP's care being extremely effective' was strongly associated with 'satisfaction with amount of PCP choice' and 'provider trust'. Having sought a second opinion(s) was associated with lower trust. 'Spoke to the PCP outside the medical office,' 'satisfaction with the insurer' and 'insurer charges less if PCP within network' were all variables associated with 'satisfaction with amount of PCP choice' (all p < .05). CONCLUSION: This study confirmed the association of 'satisfaction with amount of PCP choice' with provider trust. Results affirmed 'enough PCP choice' was a strong predictor of provider trust. 'Second opinion on PCP' may indicate distrust in the provider. Data such as 'trust in providers in general' and 'the role of provider performance information' in choice, though import in PCP choice, were not available for analysis and should be explored in future studies. Results have implications for rethinking the relationships among consumer choice, consumer behaviors in making trade-offs in PCP choice, and the role of healthcare experiences in 'satisfaction with amount of PCP choice' or 'provider trust.

NF-kappaB Mediated Transcriptional Repression of Acid Modifying Hormone Gastrin

Helicobacter pylori is a major pathogen associated with the development of gastroduodenal diseases. It has been reported that H. pylori induced pro-inflammatory cytokine IL1B is one of the various modulators of acid secretion in the gut. Earlier we reported that IL1B-activated NFkB down-regulates gastrin, the major hormonal regulator of acid secretion. In this study, the probable pathway by which IL1B induces NFkB and affects gastrin expression has been elucidated. IL1B-treated AGS cells showed nine-fold activation of MyD88 followed by phosphorylation of TAK1 within 15 min of IL1B treatment. Furthermore, it was observed that activated TAK1 significantly up-regulates the NFkB subunits p50 and p65. Ectopic expression of NFkB p65 in AGS cells resulted in about nine-fold transcriptional repression of gastrin both in the presence and absence of IL1B. The S536A mutant of NFkB p65 is significantly less effective in repressing gastrin. These observations show that a functional NFkB p65 is important for IL1B-mediated repression of gastrin. ChIP assays revealed the presence of HDAC1 and NFkB p65 along with NCoR on the gastrin promoter. Thus, the study provides mechanistic insight into the IL1B-mediated gastrin repression via NFk