The Attentional Routing Circuit: Receptive Field Modulation Through Nonlinear Dendritic Interactions

We present a model of attentional routing called the Attentional Routing Circuit (ARC) that extends an existing model of spiking neurons with dendritic nonlinearities. Specifically, we employ the Poirazi et al. (2003) pyramidal neuron in a population coding framework. ARC demonstrates that the dendritic nonlinearities can be exploited to result in selective routing, with a decrease in the number of cells needed by a factor of ~5 as compared with a linear dendrite model.

Routing of attended information occurs through the modulation of feedforward visual signals by a cortical control signal specifying the location and size of the attended target. The model is fully specified in spiking single cells. Our approach differs from past work on shifter circuits by having more efficient control, and using a more biologically detailed substrate. Our approach differs from existing models that use gain fields by providing precise hypotheses about how the control signals are generated and distributed in a hierarchical model in spiking neurons. Further, the model accounts for numerous experimental findings regarding the timing, strength and extent of attentional modulation in ventral stream areas, and the perceived contrast enhancement of attended stimuli.

To further demonstrate the plausibility of ARC, it is applied to the attention experiments of Womelsdorf et al. (2008) and tested in detail. For the simulations, the model has only two free parameters that influence its ability to match the experimental data, and without fitting, we show that it can account for the experimental observations of changes in receptive field (RF) gain and position with attention in macaques. In sum, the model provides an explanation of RF modulation as well as testable predictions about nonlinear cortical dendrites and attentional changes of receptive field properties

Xenotransplantation Clinical Trials and Equitable Patient Selection.

Xenotransplant patient selection recommendations restrict clinical trial participation to seriously ill patients for whom alternative therapies are unavailable or who will likely die while waiting for an allotransplant. Despite a scholarly consensus that this is advisable, we propose to examine this restriction. We offer three lines of criticism: (1) The risk-benefit calculation may well be unfavorable for seriously ill patients and society; (2) the guidelines conflict with criteria for equitable patient selection; and (3) the selection of seriously ill patients may compromise informed consent. We conclude by highlighting how the current guidance reveals a tension between the societal values of justice and beneficence

Genetic Disenhancement and Xenotransplantation: Diminishing Pigs’ Capacity to Experience Suffering through Genetic Engineering

One objection to xenotransplantation is that it will require the large-scale breeding, raising and killing of genetically modified pigs. The pigs will need to be raised in designated pathogen-free facilities and undergo a range of medical tests before having their organs removed and being euthanised. As a result, they will have significantly shortened life expectancies, will experience pain and suffering and be subject to a degree of social and environmental deprivation. To minimise the impact of these factors, we propose the following option for consideration—ethically defensible xenotransplantation should entail the use of genetic disenhancement if it becomes possible to do so and if that pain and suffering cannot be eliminated by other means. Despite not being a morally ideal 'solution’, it is morally better to prevent unavoidable pain until a viable non-animal alternative becomes available

Xenograft recipients and the right to withdraw from a clinical trial

Pre-clinical xenotransplantation research using transgenic pigs has begun to show some promising results and could one day offer a scalable means of addressing the organ shortage. While it is a fundamental tenet of ethical human subject research that participants have a right to withdraw from research once enrolled, several scholars have argued that the right to withdraw from xenotransplant research should be suspended because of the public health risks posed by xenozoonotic transmission. Here, we present a comprehensive examination and critical evaluation of the claim that xenotransplant recipients should be required to waive their right to withdraw from lifelong bio-surveillance. We conclude that, if xenotransplantation requires participants to waive their right to withdraw, then clinical trials may not be justifiable given the ethical and legal obstacles involved with doing so. Consequently, if clinical trials are permitted with a right to withdraw, then they may pose a significant existential and public health risk

Significance of the E-W fault system in the geodynamic evolution of the Tunisian Alpine Chain foreland. Example of the Sbiba-Cherichira fault system in central Tunisia

En Tunisie centrale, les bassins mio-plio-quaternaires de Sbiba et de Haffouz sont constitués de dépocentres délimités par des failles de direction proche de E-W, NW-SE, N070 o et N-S. Ces accidents bordiers bien identifiés en sub-surface et dont l’activité a été démontrée aux époques éo-crétacées, ont évolué durant le Néogène et le Quaternaire dans un système de décrochements en relais, alliant des structures compressives (plis N040 o à N080 o E, failles inverses, chevauchements…) et des structures distensives correspondant à des grabens et demi-grabens orientés E-W et N120 o à N150 o E. La région a été affectée du Néogène au Quaternaire inférieur par une succession de régimes tectoniques compressifs (liés aux phases tortonienne et villafranchienne) et extensifs (extension post-tectonique oligo-miocène comme dans l’ensemble du Maghreb, mais aussi existence d’une phase d’extension au Miocène terminal-Pléistocène inférieur synchrone du rifting du Bassin tyrrhénien). Cette alternance compression-extension induit plusieurs inversions de subsidence. L’étude tectonique effectuée aux abords de ces décrochements permet non seulement d’apporter des précisions sur l’évolution spatiale des déformations mais aussi d’établir les relations tectono-sédimentaires caractérisant chaque époque du Mio-Plio-Quatemaire : bassins subsidents sur les décrochements, installation de bassins lacustres sur barrages morphostructuraux, variations d’épaisseur et de faciès liées aux failles synsédimentaires

Pediatric Cardiac Xenotransplantation: Recommendations for the Ethical Design of Clinical Trials

For children with complex congenital heart problems, cardiac allotransplantation is sometimes the best therapeutic option. However, availability of hearts for pediatric patients is limited, resulting in a long and growing waitlist, and a high mortality rate while waiting. Cardiac xenotransplantation has been proposed as one therapeutic alternative for neonates and infants, either in lieu of allotransplantation or as a bridge until an allograft becomes available. Scientific and clinical developments in xenotransplantation appear likely to permit cardiac xenotransplantation clinical trials in adults in the coming years. The ethical issues around xenotransplantation of the heart and other organs and tissues have recently been examined, but to date, only limited literature is available on the ethical issues that are attendant with pediatric heart xenotransplantation. Here, we summarize the ethical issues, focusing on (i) whether cardiac xenotransplantation should proceed in adults or children first, (ii) pediatric recipient selection for initial xenotransplantation trials, (iii) special problems regarding informed consent in this context, and (iv) related psychosocial and public perception considerations. We conclude with specific recommendations regarding ethically informed design of pediatric heart xenotransplantation trials

Philosophy of Hope

The philosophy of hope centers on two interlocking sets of questions. The first concerns the nature of hope. Specific questions here include how to analyze hope, how hope motivates us, and whether there is only one type of hope. The second set concerns the value of hope. Key questions here include whether and when it is good to hope and whether there is a virtue of hope. Philosophers of hope tend to proceed from the first set of questions to the second. This is a natural approach, for one might expect that you must develop a basic understanding of what hope is before you can determine its value. The structure of this chapter thus follows this approach. But readers should not be misled: there is in fact a good deal of feedback between the two sets of questions. A theory of hope is more plausible to the extent that it fits well with plausible ideas about the value of hope. So the movement from hope’s nature to its value is one of emphasis rather than a strict, step-wise process

A differential role for the posterior cerebellum in the adaptive control of convergence eye movements

Introduction The vergence oculomotor system possesses two robust adaptive mechanisms; a fast “dynamic” and a slow “tonic” system that are both vital for single, clear and comfortable binocular vision. The neural substrates underlying these vergence adaptive mechanisms in humans is unclear. Methods We investigated the role of the posterior cerebellum in convergence adaptation using inhibitory continuous theta-burst repetitive transcranial magnetic stimulation (cTBS) within a double-blind, sham controlled design while eye movements were recorded at 250hz via infrared oculography. Results In a preliminary experiment we validated our stimulation protocols by reproducing results from previous work on saccadic adaptation during the classic double-step adaptive shortening paradigm. Following this, across a series of three separate experiments we observed a clear dissociation in the effect of cTBS on convergence adaptation. Dynamic adaptation was substantially reduced while tonic adaptation was unaffected. Baseline dynamic fusional vergence response were also unaffected by stimulation. Conclusions These results indicate a differential role for the posterior cerebellum in the adaptive control of convergence eye movements and provide initial evidence that repetitive transcranial magnetic stimulation is a viable tool to investigate the neurophysiology of vergence control. The results are discussed in the context of the current models of implicit motor adaptation of vergence and their application to clinical populations and technology design in virtual and augmented head mounted display architectures. Significance statement The cerebellum plays a critical role in the adaptive control of motor systems. Vergence eye movements shift our gaze in depth allowing us to see in 3D and exhibit two distinct adaptive mechanisms that are engaged under a range of conditions including reading, wearing head-mounted displays and using a new spectacle prescription. It is unclear what role the cerebellum plays in these adaptive mechanisms. To answer this, we temporarily disrupted the function of the posterior cerebellum using non-invasive brain stimulation and report impairment of only one adaptive mechanism, providing evidence for neural compartmentalization. The results have implications for vergence control models and applications to comfort and experience studies in head-mounted displays and the rehabilitation of clinical populations exhibiting vergence dysfunctions.National Science and Engineering Research Council of Canada || Canadian Foundation of Innovators || American Academy of Optometry Foundation || Canadian Institutes for Health Research

Towards a Mathematical Theory of Cortical Micro-circuits

The theoretical setting of hierarchical Bayesian inference is gaining acceptance as a framework for understanding cortical computation. In this paper, we describe how Bayesian belief propagation in a spatio-temporal hierarchical model, called Hierarchical Temporal Memory (HTM), can lead to a mathematical model for cortical circuits. An HTM node is abstracted using a coincidence detector and a mixture of Markov chains. Bayesian belief propagation equations for such an HTM node define a set of functional constraints for a neuronal implementation. Anatomical data provide a contrasting set of organizational constraints. The combination of these two constraints suggests a theoretically derived interpretation for many anatomical and physiological features and predicts several others. We describe the pattern recognition capabilities of HTM networks and demonstrate the application of the derived circuits for modeling the subjective contour effect. We also discuss how the theory and the circuit can be extended to explain cortical features that are not explained by the current model and describe testable predictions that can be derived from the model