Neuronal Variability during Handwriting: Lognormal Distribution

We examined time-dependent statistical properties of electromyographic (EMG) signals recorded from intrinsic hand muscles during handwriting. Our analysis showed that trial-to-trial neuronal variability of EMG signals is well described by the lognormal distribution clearly distinguished from the Gaussian (normal) distribution. This finding indicates that EMG formation cannot be described by a conventional model where the signal is normally distributed because it is composed by summation of many random sources. We found that the variability of temporal parameters of handwriting - handwriting duration and response time - is also well described by a lognormal distribution. Although, the exact mechanism of lognormal statistics remains an open question, the results obtained should significantly impact experimental research, theoretical modeling and bioengineering applications of motor networks. In particular, our results suggest that accounting for lognormal distribution of EMGs can improve biomimetic systems that strive to reproduce EMG signals in artificial actuators

Stress induced polarization of immune-neuroendocrine phenotypes in Gallus gallus

Immune-neuroendocrine phenotypes (INPs) stand for population subgroups differing in immune-neuroendocrine interactions. While mammalian INPs have been characterized thoroughly in rats and humans, avian INPs were only recently described in Coturnix coturnix (quail). To assess the scope of this biological phenomenon, herein we characterized INPs in Gallus gallus (a domestic hen strain submitted to a very long history of strong selective breeding pressure) and evaluated whether a social chronic stress challenge modulates the individuals’ interplay affecting the INP subsets and distribution. Evaluating plasmatic basal corticosterone, interferon-γ and interleukin-4 concentrations, innate/acquired leukocyte ratio, PHA-P skin-swelling and induced antibody responses, two opposite INP profiles were found: LEWIS-like (15% of the population) and FISCHER-like (16%) hens. After chronic stress, an increment of about 12% in each polarized INP frequency was found at expenses of a reduction in the number of birds with intermediate responses. Results show that polarized INPs are also a phenomenon occurring in hens. The observed inter-individual variation suggest that, even after a considerable selection process, the population is still well prepared to deal with a variety of immune-neuroendocrine challenges. Stress promoted disruptive effects, leading to a more balanced INPs distribution, which represents a new substrate for challenging situations.Fil: Nazar, Franco Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Estevez, Inma. Centro de Investigación. Neiker - Tecnalia; EspañaFil: Correa, Silvia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Marin, Raul Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentin

Biomechanical evaluation of immediate stability with rectangular versus cylindrical interbody cages in stabilization of the lumbar spine

BACKGROUND: Recent cadaver studies show stability against axial rotation with a cylindrical cage is marginally superior to a rectangular cage. The purpose of this biomechanical study in cadaver spine was to evaluate the stability of a new rectangular titanium cage design, which has teeth similar to the threads of cylindrical cages to engage the endplates. METHODS: Ten motion segments (five L2-3, five L4-5) were tested. From each cadaver spine, one motion segment was fixed with a pair of cylindrical cages (BAK, Sulzer Medica) and the other with paired rectangular cages (Rotafix, Corin Spinal). Each specimen was tested in an unconstrained state, after cage introduction and after additional posterior translaminar screw fixation. The range of motion (ROM) in flexion-extension, lateral bending, and rotation was tested in a materials testing machine, with +/- 5 Nm cyclical load over 10 sec per cycle; data from the third cycle was captured for analysis. RESULTS: ROM in all directions was significantly reduced (p < 0.05) with both types of cages. There was no significant difference in reduction of ROM in flexion-extension (p = 0.6) and rotation (p = 0.92) between the two cage groups, but stability in lateral bending was marginally superior with the rectangular cages (p = 0.11). Additional posterior fixation further reduced the ROM significantly (p < 0.05) in most directions in both cage groups, but did not show any difference between the cage groups. CONCLUSIONS: There was no significant difference in immediate stability in any direction between the threaded cylindrical cage and the new design of the rectangular cage with endplate teeth

Refinement and Pattern Formation in Neural Circuits by the Interaction of Traveling Waves with Spike-Timing Dependent Plasticity

Traveling waves in the developing brain are a prominent source of highly correlated spiking activity that may instruct the refinement of neural circuits. A candidate mechanism for mediating such refinement is spike-timing dependent plasticity (STDP), which translates correlated activity patterns into changes in synaptic strength. To assess the potential of these phenomena to build useful structure in developing neural circuits, we examined the interaction of wave activity with STDP rules in simple, biologically plausible models of spiking neurons. We derive an expression for the synaptic strength dynamics showing that, by mapping the time dependence of STDP into spatial interactions, traveling waves can build periodic synaptic connectivity patterns into feedforward circuits with a broad class of experimentally observed STDP rules. The spatial scale of the connectivity patterns increases with wave speed and STDP time constants. We verify these results with simulations and demonstrate their robustness to likely sources of noise. We show how this pattern formation ability, which is analogous to solutions of reaction-diffusion systems that have been widely applied to biological pattern formation, can be harnessed to instruct the refinement of postsynaptic receptive fields. Our results hold for rich, complex wave patterns in two dimensions and over several orders of magnitude in wave speeds and STDP time constants, and they provide predictions that can be tested under existing experimental paradigms. Our model generalizes across brain areas and STDP rules, allowing broad application to the ubiquitous occurrence of traveling waves and to wave-like activity patterns induced by moving stimuli

A Multi-Component Model of the Developing Retinocollicular Pathway Incorporating Axonal and Synaptic Growth

During development, neurons extend axons to different brain areas and produce stereotypical patterns of connections. The mechanisms underlying this process have been intensively studied in the visual system, where retinal neurons form retinotopic maps in the thalamus and superior colliculus. The mechanisms active in map formation include molecular guidance cues, trophic factor release, spontaneous neural activity, spike-timing dependent plasticity (STDP), synapse creation and retraction, and axon growth, branching and retraction. To investigate how these mechanisms interact, a multi-component model of the developing retinocollicular pathway was produced based on phenomenological approximations of each of these mechanisms. Core assumptions of the model were that the probabilities of axonal branching and synaptic growth are highest where the combined influences of chemoaffinity and trophic factor cues are highest, and that activity-dependent release of trophic factors acts to stabilize synapses. Based on these behaviors, model axons produced morphologically realistic growth patterns and projected to retinotopically correct locations in the colliculus. Findings of the model include that STDP, gradient detection by axonal growth cones and lateral connectivity among collicular neurons were not necessary for refinement, and that the instructive cues for axonal growth appear to be mediated first by molecular guidance and then by neural activity. Although complex, the model appears to be insensitive to variations in how the component developmental mechanisms are implemented. Activity, molecular guidance and the growth and retraction of axons and synapses are common features of neural development, and the findings of this study may have relevance beyond organization in the retinocollicular pathway

Spike-Triggered Covariance Analysis Reveals Phenomenological Diversity of Contrast Adaptation in the Retina

When visual contrast changes, retinal ganglion cells adapt by adjusting their sensitivity as well as their temporal filtering characteristics. The latter has classically been described by contrast-induced gain changes that depend on temporal frequency. Here, we explored a new perspective on contrast-induced changes in temporal filtering by using spike-triggered covariance analysis to extract multiple parallel temporal filters for individual ganglion cells. Based on multielectrode-array recordings from ganglion cells in the isolated salamander retina, we found that contrast adaptation of temporal filtering can largely be captured by contrast-invariant sets of filters with contrast-dependent weights. Moreover, differences among the ganglion cells in the filter sets and their contrast-dependent contributions allowed us to phenomenologically distinguish three types of filter changes. The first type is characterized by newly emerging features at higher contrast, which can be reproduced by computational models that contain response-triggered gain-control mechanisms. The second type follows from stronger adaptation in the Off pathway as compared to the On pathway in On-Off-type ganglion cells. Finally, we found that, in a subset of neurons, contrast-induced filter changes are governed by particularly strong spike-timing dynamics, in particular by pronounced stimulus-dependent latency shifts that can be observed in these cells. Together, our results show that the contrast dependence of temporal filtering in retinal ganglion cells has a multifaceted phenomenology and that a multi-filter analysis can provide a useful basis for capturing the underlying signal-processing dynamics

Primary progressive aphasia: a clinical approach

This work was supported by the Alzheimer’s Society (AS-PG-16-007), the National Institute for Health Research University College London Hospitals Biomedical Research Centre and the UCL Leonard Wolfson Experimental Neurology Centre (PR/ylr/18575). Individual authors were supported by the Leonard Wolfson Foundation (Clinical Research Fellowship to CRM), the National Institute for Health Research (NIHR Doctoral Training Fellowship to AV), the National Brain Appeal–Frontotemporal Dementia Research Fund (CNC) and the Medical Research Council (PhD Studentships to CJDH and RLB, MRC Research Training Fellowship to PDF, MRC Clinician Scientist to JDR). MNR and NCF are NIHR Senior Investigators. SJC is supported by Grants from ESRC-NIHR (ES/L001810/1), EPSRC (EP/M006093/1) and Wellcome Trust (200783). JDW was supported by a Wellcome Trust Senior Research Fellowship in Clinical Science (091673/Z/10/Z)

Cryptococcal meningitis: epidemiology, immunology, diagnosis and therapy.

HIV-associated cryptococcal meningitis is by far the most common cause of adult meningitis in many areas of the world that have high HIV seroprevalence. In most areas in Sub-Saharan Africa, the incidence of cryptococcal meningitis is not decreasing despite availability of antiretroviral therapy, because of issues of adherence and retention in HIV care. In addition, cryptococcal meningitis in HIV-seronegative individuals is a substantial problem: the risk of cryptococcal infection is increased in transplant recipients and other individuals with defects in cell-mediated immunity, and cryptococcosis is also reported in the apparently immunocompetent. Despite therapy, mortality rates in these groups are high. Over the past 5 years, advances have been made in rapid point-of-care diagnosis and early detection of cryptococcal antigen in the blood. These advances have enabled development of screening and pre-emptive treatment strategies aimed at preventing the development of clinical infection in patients with late-stage HIV infection. Progress in optimizing antifungal combinations has been aided by evaluation of the clearance rate of infection by using serial quantitative cultures of cerebrospinal fluid (CSF). Measurement and management of raised CSF pressure, a common complication, is a vital component of care. In addition, we now better understand protective immune responses in HIV-associated cases, immunogenetic predisposition to infection, and the role of immune-mediated pathology in patients with non-HIV associated infection and in the context of HIV-associated immune reconstitution reactions