Integrate and Fire Neural Networks, Piecewise Contractive Maps and Limit Cycles

We study the global dynamics of integrate and fire neural networks composed of an arbitrary number of identical neurons interacting by inhibition and excitation. We prove that if the interactions are strong enough, then the support of the stable asymptotic dynamics consists of limit cycles. We also find sufficient conditions for the synchronization of networks containing excitatory neurons. The proofs are based on the analysis of the equivalent dynamics of a piecewise continuous Poincar\'e map associated to the system. We show that for strong interactions the Poincar\'e map is piecewise contractive. Using this contraction property, we prove that there exist a countable number of limit cycles attracting all the orbits dropping into the stable subset of the phase space. This result applies not only to the Poincar\'e map under study, but also to a wide class of general n-dimensional piecewise contractive maps.Comment: 46 pages. In this version we added many comments suggested by the referees all along the paper, we changed the introduction and the section containing the conclusions. The final version will appear in Journal of Mathematical Biology of SPRINGER and will be available at http://www.springerlink.com/content/0303-681

A Markovian event-based framework for stochastic spiking neural networks

In spiking neural networks, the information is conveyed by the spike times, that depend on the intrinsic dynamics of each neuron, the input they receive and on the connections between neurons. In this article we study the Markovian nature of the sequence of spike times in stochastic neural networks, and in particular the ability to deduce from a spike train the next spike time, and therefore produce a description of the network activity only based on the spike times regardless of the membrane potential process. To study this question in a rigorous manner, we introduce and study an event-based description of networks of noisy integrate-and-fire neurons, i.e. that is based on the computation of the spike times. We show that the firing times of the neurons in the networks constitute a Markov chain, whose transition probability is related to the probability distribution of the interspike interval of the neurons in the network. In the cases where the Markovian model can be developed, the transition probability is explicitly derived in such classical cases of neural networks as the linear integrate-and-fire neuron models with excitatory and inhibitory interactions, for different types of synapses, possibly featuring noisy synaptic integration, transmission delays and absolute and relative refractory period. This covers most of the cases that have been investigated in the event-based description of spiking deterministic neural networks

Alterations in vascular function in primary aldosteronism - a cardiovascular magnetic resonance imaging study

Introduction: Excess aldosterone is associated with increased cardiovascular risk. Aldosterone has a permissive effect on vascular fibrosis. Cardiovascular magnetic resonance imaging (CMR) allows study of vascular function by measuring aortic distensibility. We compared aortic distensibility in primary aldosteronism (PA), essential hypertension (EH) and normal controls and explored the relationship between aortic distensibility and pulse wave velocity (PWV).<p></p> Methods: We studied PA (n=14) and EH (n=33) subjects and age-matched healthy controls (n=17) with CMR, including measurement of aortic distensibility, and measured PWV using applanation tonometry. At recruitment, PA and EH patients had similar blood pressure and left ventricular mass.<p></p> Results: Subjects with PA had significantly lower aortic distensibilty and higher PWV compared to EH and healthy controls. These changes were independent of other factors associated with reduced aortic distensibility, including aging. There was a significant relationship between increasing aortic stiffness and age in keeping with physical and vascular aging. As expected, aortic distensibility and PWV were closely correlated.<p></p> Conclusion: These results demonstrate that PA patients display increased arterial stiffness compared to EH, independent of vascular aging. The implication is that aldosterone invokes functional impairment of arterial function. The long-term implications of arterial stiffening in aldosterone excess require further study.<p></p&gt

Aerosolized BC-819 Inhibits Primary but Not Secondary Lung Cancer Growth

Despite numerous efforts, drug based treatments for patients suffering from lung cancer remains poor. As a promising alternative, we investigated the therapeutic potential of BC-819 for the treatment of lung cancer in mouse tumor models. BC-819 is a novel plasmid DNA which encodes for the A-fragment of Diphtheria toxin and has previously been shown to successfully inhibit tumor growth in human clinical study of bladder carcinoma. In a first set of experiments, we examined in vitro efficacy of BC-819 in human lung cancer cell-lines NCI-H460, NCI-H358 and A549, which revealed >90% reduction of cell growth. In vivo efficacy was examined in an orthotopic mouse xenograft lung cancer model and in a lung metastasis model using luminescent A549-C8-luc adenocarcinoma cells. These cells resulted in peri- and intra-bronchiolar tumors upon intrabronchial application and parenchymal tumors upon intravenous injection, respectively. Mice suffering from these lung tumors were treated with BC-819, complexed to branched polyethylenimine (PEI) and aerosolized to the mice once per week for a period of 10 weeks. Using this regimen, growth of intrabronchially induced lung tumors was significantly inhibited (p = 0.01), whereas no effect could be observed in mice suffering from lung metastasis. In summary, we suggest that aerosolized PEI/BC-819 is capable of reducing growth only in tumors arising from the luminal part of the airways and are therefore directly accessible for inhaled BC-819

Immunoblot analysis of the seroreactivity to recombinant Borrelia burgdorferi sensu lato antigens, including VlsE, in the long-term course of treated patients with Erythema migrans

Objective: We evaluated whether immunoblotting is capable of substantiating the posttreatment clinical assessment of patients with erythema migrans ( EM), the hallmark of early Lyme borreliosis. Methods: In 50 patients, seroreactivity to different antigens of Borrelia burgdorferi sensu lato was analyzed by a recombinant immunoblot test (IB) in consecutive serum samples from a minimum follow-up period of 1 year. Antigens in the IgG test were decorin- binding protein A, internal fragment of p41 (p41i), outer surface protein C (OspC), p39, variable major protein-like sequence expressed (VlsE), p58 and p100; those in the IgM test were p41i, OspC and p39. Immune responses were correlated with clinical and treatment-related parameters. Results: Positive IB results were found in 50% before, in 57% directly after therapy and in 44% by the end of the follow-up for the IgG class, and in 36, 43 and 12% for the IgM class. In acute and convalescence phase sera, VlsE was most immunogenic on IgG testing 60 and 70%), and p41i (46 and 57%) and OspC (40 and 57%) for the IgM class. By the end of the follow-up, only the anti-p41i lgM response was significantly decreased to 24%. Conclusions: No correlation was found between IB results and treatment-related parameters. Thus, immunoblotting does not add to the clinical assessment of EM patients after treatment. Copyright (c) 2008 S. Karger AG, Basel

Intrinsic gain modulation and adaptive neural coding

In many cases, the computation of a neural system can be reduced to a receptive field, or a set of linear filters, and a thresholding function, or gain curve, which determines the firing probability; this is known as a linear/nonlinear model. In some forms of sensory adaptation, these linear filters and gain curve adjust very rapidly to changes in the variance of a randomly varying driving input. An apparently similar but previously unrelated issue is the observation of gain control by background noise in cortical neurons: the slope of the firing rate vs current (f-I) curve changes with the variance of background random input. Here, we show a direct correspondence between these two observations by relating variance-dependent changes in the gain of f-I curves to characteristics of the changing empirical linear/nonlinear model obtained by sampling. In the case that the underlying system is fixed, we derive relationships relating the change of the gain with respect to both mean and variance with the receptive fields derived from reverse correlation on a white noise stimulus. Using two conductance-based model neurons that display distinct gain modulation properties through a simple change in parameters, we show that coding properties of both these models quantitatively satisfy the predicted relationships. Our results describe how both variance-dependent gain modulation and adaptive neural computation result from intrinsic nonlinearity.Comment: 24 pages, 4 figures, 1 supporting informatio

APOLO-Bari, an internet-based program for longitudinal support of bariatric surgery patients: study protocol for a randomized controlled trial

Background: Despite evidence of successful weight loss for bariatric surgery patients, some patients experience considerable weight regain over the long term. Given the strong association between post-surgery health behaviors and outcomes, aftercare intervention to address key behaviors appears to be a reasonable relapse-prevention strategy. As the burden of obesity rates increases in healthcare centers, an internet-based program appears to be a reasonable strategy for supporting bariatric surgery patients in the long term. The primary purpose of the current project is to develop and test the efficacy and perceived utility of APOLO-Bari.Methods/design: This study is a randomized control trial, which will be conducted in two hospital centers in the North of Portugal; it includes a control group receiving treatment as usual and an intervention group receiving the APOLO-Bari program for one year in addition to treatment as usual. A total of 180 male and female participants who underwent bariatric surgery (gastric sleeve or gastric bypass surgery) for 12 to 20 months will be recruited. Both groups will complete a similar set of questionnaires at baseline, every 4 months until the end of the intervention, and at 6 and 12 months follow-up. Assessment includes anthropometric variables and psychological self-report measures. The primary outcome measure will be weight regain measured at the end of treatment, and at 6 and 12 months follow-up. The secondary aims are to test the cost-effectiveness of the intervention and to investigate psychological predictors and trajectories of weight regain. APOLO-Bari was developed to address the weight regain problem in the bariatric population by offering additional guidance to bariatric patients during the postoperative period. The program includes: (a) a psychoeducational cognitive-behavioral-based self-help manual, (b) a weekly feedback messaging system that sends a feedback statement related to information reported by the participant, and (c) interactive chat sessions scheduled witThis research was partially supported by the Fundacao para a Ciencia e a Tecnologia through a European Union COMPETE program grant to Eva Conceicao (IF/01219/2014 and PTDC/MHC-PCL/4974/2012), a doctoral scholarship to Ana Pinto-Bastos (SFRH/BD/104159/2014), a doctoral scholarship to Sofia Ramalho (SFRH/BD/104182/2014), and a postdoctoral scholarship to Ana Rita Vaz (SFRH/BPD/94490/2013), co-financed by FEDER under the PT2020 Partnership Agreement (UID/PSI/01662/2013).info:eu-repo/semantics/publishedVersio