Impact of Renal Impairment on Beta-Blocker Efficacy in Patients With Heart Failure.

BACKGROUND: Moderate and moderately severe renal impairment are common in patients with heart failure and reduced ejection fraction, but whether beta-blockers are effective is unclear, leading to underuse of life-saving therapy. OBJECTIVES: This study sought to investigate patient prognosis and the efficacy of beta-blockers according to renal function using estimated glomerular filtration rate (eGFR). METHODS: Analysis of 16,740 individual patients with left ventricular ejection fraction <50% from 10 double-blind, placebo-controlled trials was performed. The authors report all-cause mortality on an intention-to-treat basis, adjusted for baseline covariates and stratified by heart rhythm. RESULTS: Median eGFR at baseline was 63 (interquartile range: 50 to 77) ml/min/1.73 m2; 4,584 patients (27.4%) had eGFR 45 to 59 ml/min/1.73 m2, and 2,286 (13.7%) 30 to 44 ml/min/1.73 m2. Over a median follow-up of 1.3 years, eGFR was independently associated with mortality, with a 12% higher risk of death for every 10 ml/min/1.73 m2 lower eGFR (95% confidence interval [CI]: 10% to 15%; p < 0.001). In 13,861 patients in sinus rhythm, beta-blockers reduced mortality versus placebo; adjusted hazard ratio (HR): 0.73 for eGFR 45 to 59 ml/min/1.73 m2 (95% CI: 0.62 to 0.86; p < 0.001) and 0.71 for eGFR 30 to 44 ml/min/1.73 m2 (95% CI: 0.58 to 0.87; p = 0.001). The authors observed no deterioration in renal function over time in patients with moderate or moderately severe renal impairment, no difference in adverse events comparing beta-blockers with placebo, and higher mortality in patients with worsening renal function on follow-up. Due to exclusion criteria, there were insufficient patients with severe renal dysfunction (eGFR <30 ml/min/1.73 m2) to draw conclusions. In 2,879 patients with atrial fibrillation, there was no reduction in mortality with beta-blockers at any level of eGFR. CONCLUSIONS: Patients with heart failure, left ventricular ejection fraction <50% and sinus rhythm should receive beta-blocker therapy even with moderate or moderately severe renal dysfunction

A modelling study of beta-amyloid induced change in hippocampal theta rhythm

Many dementia cases, such as Alzheimer&#x2019;s disease (AD), are characterized by an increase in low frequency field potential oscillations. However, a definitive understanding of the effects of the beta-Amyloid peptide, which is a main marker of AD, on the low frequency theta rhythm (4-7Hz) is still unavailable. In this work, we investigate the neural mechanisms associated with beta-Amyloid toxicity using a conductance-based neuronal network model of the hippocampus CA1 region. We simulate the effects of beta-Amyloid on the A-type fast inactivating K+ channel by modulating the maximum conductance of the current in pyramidal cells, denoted by gA. Our simulation results demonstrate that as gA decreases (through A[beta]&#xd;&#xa;blockage), the theta band power first increases then decreases. Thus there exists a value of gA that maximizes the theta band power. The neuronal and network mechanism underlying the change in theta rhythm is systematically analyzed. We show that the increase in theta power is due to the improved synchronization of pyramidal neurons, and the theta decrease is induced by the faster depolarisation of pyramidal neurons

Cross-frequency phase-amplitude coupling as a mechanism for temporal orienting of attention in childhood

Temporal orienting of attention operates by biasing the allocation of cognitive and motor resources in specific moments in time, resulting in the improved processing of information from expected compared with unexpected targets. Recent findings have shown that temporal orienting operates relatively early across development, suggesting that this attentional mechanism plays a core role for human cognition. However, the exact neurophysiological mechanisms allowing children to attune their attention over time are not well understood. In this study, we presented 8- to 12-year-old children with a temporal cueing task designed to test (1) whether anticipatory oscillatory dynamics predict children's behavioral performance on a trial-by-trial basis and (2) whether anticipatory oscillatory neural activity may be supported by cross-frequency phase–amplitude coupling as previously shown in adults. Crucially, we found that, similar to what has been reported in adults, children's ongoing beta rhythm was strongly coupled with their theta rhythm and that the strength of this coupling distinguished validly cued temporal intervals, relative to neutral cued trials. In addition, in long trials, there was an inverse correlation between oscillatory beta power and children's trial-by-trial reaction, consistent with oscillatory beta power reflecting better response preparation. These findings provide the first experimental evidence that temporal attention in children operates by exploiting oscillatory mechanism. </jats:p

Discovering Functional Communities in Dynamical Networks

Many networks are important because they are substrates for dynamical systems, and their pattern of functional connectivity can itself be dynamic -- they can functionally reorganize, even if their underlying anatomical structure remains fixed. However, the recent rapid progress in discovering the community structure of networks has overwhelmingly focused on that constant anatomical connectivity. In this paper, we lay out the problem of discovering_functional communities_, and describe an approach to doing so. This method combines recent work on measuring information sharing across stochastic networks with an existing and successful community-discovery algorithm for weighted networks. We illustrate it with an application to a large biophysical model of the transition from beta to gamma rhythms in the hippocampus.Comment: 18 pages, 4 figures, Springer "Lecture Notes in Computer Science" style. Forthcoming in the proceedings of the workshop "Statistical Network Analysis: Models, Issues and New Directions", at ICML 2006. Version 2: small clarifications, typo corrections, added referenc

Gamma rhythms and beta rhythms have different synchronization properties

Experimental and modeling efforts suggest that rhythms in the CA1 region of the hippocampus that are in the beta range (12-29 Hz) have a different dynamical structure than that of gamma (30-70 Hz). We use a simplified model to show that the different rhythms employ different dynamical mechanisms to synchronize, based on different ionic currents. The beta frequency is able to synchronize over long conduction delays (corresponding to signals traveling a significant distance in the brain) that apparently cannot be tolerated by gamma rhythms. The synchronization properties are consistent with data suggesting that gamma rhythms are used for relatively local computations whereas beta rhythms are used for higher level interactions involving more distant structures

Neurosystems: brain rhythms and cognitive processing

Neuronal rhythms are ubiquitous features of brain dynamics, and are highly correlated with cognitive processing. However, the relationship between the physiological mechanisms producing these rhythms and the functions associated with the rhythms remains mysterious. This article investigates the contributions of rhythms to basic cognitive computations (such as filtering signals by coherence and/or frequency) and to major cognitive functions (such as attention and multi-modal coordination). We offer support to the premise that the physiology underlying brain rhythms plays an essential role in how these rhythms facilitate some cognitive operations.098352 - Wellcome Trust; 5R01NS067199 - NINDS NIH HH

Rate-Control or Rhythm-Contol: Where do we stand?

Atrial fibrillation is the most common sustained rhythm disturbance and its prevalence is increasing worldwide due to the progressive aging of the population. Current guidelines clearly depict the gold standard management of acute symptomatic atrial fibrillation but the best-long term approach for first or recurrent atrial fibrillation is still debated with regard to quality of life, risk of new hospitalizations, and possible disabling complications, such as thromboembolic stroke, major bleeds and death. Some authors propose that regaining sinus rhythm in all cases, thus re-establishing a physiologic cardiac function not requiring a prolonged antithrombotic therapy, avoids the threat of intracranial or extracranial haemorrhages due to Vitamin K antagonists or aspirin. On the contrary, advocates of a rate control approach with an accurate antithrombotic prophylaxis propose that such a strategy may avoid the risk of cardiovascular and non cardiovascular side effects related to antiarrhythmic drugs. This review aims to explore the state of our knowledge in order to summarize evidences and issues that need to be furthermore clarified

Hybrid brain-computer interface and functional electrical stimulation for sensorimotor training in participants with tetraplegia: a proof-of-concept study

Background and Purpose: Impaired hand function decreases quality of life in persons with tetraplegia. We tested functional electrical stimulation (FES) controlled by a hybrid brain-computer interface (BCI) for improving hand function in participants with tetraplegia. Methods: Two participants with subacute tetraplegia (participant 1: C5 Brown-Sequard syndrome, participant 2: complete C5 lesion) took part in this proof-of-concept study. The goal was to determine whether the BCI system could drive the FES device by accurately classifying participants' intent (open or close the hand). Participants 1 and 2 received 10 sessions and 4 sessions of BCI-FES, respectively. A novel time-switch BCI strategy based on motor imagery was used to activate the FES. In one session, we tested a hybrid BCI-FES based on 2 spontaneously generated brain rhythms: a sensory-motor rhythm during motor imagery to activate a stimulator and occipital alpha rhythms to deactivate the stimulator. Participants received BCI-FES therapy 2 to 3 times a week in addition to conventional therapy. Imagery ability and muscle strength were measured before and after treatment. Results: Visual feedback was associated with a 4-fold increase of brain response during motor imagery in both participants. For participant 1, classification accuracy (open/closed) for motor imagery-based BCI was 83.5% (left hand) and 83.8% (right hand); participant 2 had a classification accuracy of 83.8% for the right hand. Participant 1 had moderate improvement in muscle strength, while there was no change for participant 2. Discussion and Conclusion: We demonstrated feasibility of BCI-FES, using 2 naturally generated brain rhythms. Studies on a larger number of participants are needed to separate the effects of BCI training from effects of conventional therapy