Monitoring the past and choosing the future: the prefrontal cortical influences on voluntary action.

Choosing between equivalent response options requires the resolution of ambiguity. One could facilitate such decisions by monitoring previous actions and implementing transient or arbitrary rules to differentiate response options. This would reduce the entropy of chosen actions. We examined voluntary action decisions during magnetoencephalography, identifying the spatiotemporal correlates of stimulus- and choice-entropy. Negative correlations between frontotemporal activity and entropy of past trials were observed after participants' responses, reflecting sequential monitoring of recent events. In contrast, choice entropy correlated negatively with prefrontal activity, before and after participants' response, consistent with transient activation of latent response-sets ahead of a decision and updating the monitor of recent decisions after responding. Individual differences in current choices were related to the strength of the prefrontal signals that reflect monitoring of the statistical regularities in previous events. Together, these results explain individual expressions of voluntary action, through differential engagement of prefrontal areas to guide sequential decisions

iElectrodes: A Comprehensive Open-Source Toolbox for Depth and Subdural Grid Electrode Localization

The localization of intracranial electrodes is a fundamental step in the analysis of invasive electroencephalography (EEG) recordings in research and clinical practice. The conclusions reached from the analysis of these recordings rely on the accuracy of electrode localization in relationship to brain anatomy. However, currently available techniques for localizing electrodes from magnetic resonance (MR) and/or computerized tomography (CT) images are time consuming and/or limited to particular electrode types or shapes. Here we present iElectrodes, an open-source toolbox that provides robust and accurate semi-automatic localization of both subdural grids and depth electrodes. Using pre- and post-implantation images, the method takes 2–3 min to localize the coordinates in each electrode array and automatically number the electrodes. The proposed pre-processing pipeline allows one to work in a normalized space and to automatically obtain anatomical labels of the localized electrodes without neuroimaging experts. We validated the method with data from 22 patients implanted with a total of 1,242 electrodes. We show that localization distances were within 0.56 mm of those achieved by experienced manual evaluators. iElectrodes provided additional advantages in terms of robustness (even with severe perioperative cerebral distortions), speed (less than half the operator time compared to expert manual localization), simplicity, utility across multiple electrode types (surface and depth electrodes) and all brain regions.This work was supported by Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) to AB and SK, Agencia Nacional de Promoción Científica y Tecnológica (PIDC 53/2012 and PICT 0775/2012 to AB, JP, SK, and PICT 1232/2014 to CM), Universidad Nacional Arturo Jauretche Investiga 2014 to AB and SK, Comisión de Investigaciones Científicas (CIC) to CHM, Medical Research Council (MC-A060-5PQ30 to JR and a Doctoral Training award to HP), Wellcome Trust (103838 Senior Research Fellowship to JR, Biomedical Research Fellowship; WT093811MA to TB), the James F. McDonnell Foundation 21st Century Science Initiative: Understanding Human Cognition to JR

Evolution of predator dispersal in relation to spatio-temporal prey dynamics : how not to get stuck in the wrong place!

Peer reviewedPublisher PD

A novel isolator-based system promotes viability of human embryos during laboratory processing

In vitro fertilisation (IVF) and related technologies are arguably the most challenging of all cell culture applications. The starting material is a single cell from which one aims to produce an embryo capable of establishing a pregnancy eventually leading to a live birth. Laboratory processing during IVF treatment requires open manipulations of gametes and embryos, which typically involves exposure to ambient conditions. To reduce the risk of cellular stress, we have developed a totally enclosed system of interlinked isolator-based workstations designed to maintain oocytes and embryos in a physiological environment throughout the IVF process. Comparison of clinical and laboratory data before and after the introduction of the new system revealed that significantly more embryos developed to the blastocyst stage in the enclosed isolator-based system compared with conventional open-fronted laminar flow hoods. Moreover, blastocysts produced in the isolator-based system contained significantly more cells and their development was accelerated. Consistent with this, the introduction of the enclosed system was accompanied by a significant increase in the clinical pregnancy rate and in the proportion of embryos implanting following transfer to the uterus. The data indicate that protection from ambient conditions promotes improved development of human embryos. Importantly, we found that it was entirely feasible to conduct all IVF-related procedures in the isolator-based workstations

The flying buttress construct for posterior spinopelvic fixation: a technical note

<p>Abstract</p> <p>Background</p> <p>Posterior fusion of the spine to the pelvis in paediatric and adult spinal deformity is still challenging. Especially assembling of the posterior rod construct to the iliac screw is considered technically difficult. A variety of spinopelvic fixation techniques have been developed. However, extreme bending of the longitudinal rods or the use of 90-degree lateral offset connectors proved to be difficult, because the angle between the rod and the iliac screw varies from patient to patient.</p> <p>Methods</p> <p>We adopted a new spinopelvic fixation system, in which iliac screws are side-to-side connected to the posterior thoracolumbar rod construct, independent of the angle between the rod and the iliac screw. Open angled parallel connectors are used to connect short iliac rods from the posterior rod construct to the iliac screws at both sides. The construct resembles in form and function an architectural Flying Buttress, or lateral support arches, used in Gothic cathedrals.</p> <p>Results and discussion</p> <p>Three different cases that illustrate the Flying Buttress construct for spinopelvic fixation are reported here with the clinical details, radiographic findings and surgical technique used.</p> <p>Conclusion</p> <p>The Flying Buttress construct may offer an alternative surgical option for spinopelvic fixation in circumstances wherein coronal or sagittal balance cannot be achieved, for example in cases with significant residual pelvic obliquity, or in revision spinal surgery for failed lumbosacral fusion.</p

GABAergic cortical network physiology in frontotemporal lobar degeneration

This is the final version. Available from Oxford University Press via the DOI in this record.The extended DCM is available at https://gitlab.com/tallie/edcm and works in conjunction with the modified SPM12 scripts provided therein. Source data may be available for non-commercial research purposes, on request from the senior author, subject to limitations to protect participant identity.The clinical syndromes caused by frontotemporal lobar degeneration are heterogeneous, including the behavioural variant frontotemporal dementia (bvFTD) and progressive supranuclear palsy. Although pathologically distinct, they share many behavioural, cognitive and physiological features, which may in part arise from common deficits of major neurotransmitters such as γ-aminobutyric acid (GABA). Here, we quantify the GABAergic impairment and its restoration with dynamic causal modelling of a double-blind placebo-controlled crossover pharmaco-magnetoencephalography study. We analysed 17 patients with bvFTD, 15 patients with progressive supranuclear palsy, and 20 healthy age- and gender-matched controls. In addition to neuropsychological assessment and structural MRI, participants undertook two magnetoencephalography sessions using a roving auditory oddball paradigm: once on placebo and once on 10 mg of the oral GABA reuptake inhibitor tiagabine. A subgroup underwent ultrahigh-field magnetic resonance spectroscopy measurement of GABA concentration, which was reduced among patients. We identified deficits in frontotemporal processing using conductance-based biophysical models of local and global neuronal networks. The clinical relevance of this physiological deficit is indicated by the correlation between top-down connectivity from frontal to temporal cortex and clinical measures of cognitive and behavioural change. A critical validation of the biophysical modelling approach was evidence from parametric empirical Bayes analysis that GABA levels in patients, measured by spectroscopy, were related to posterior estimates of patients’ GABAergic synaptic connectivity. Further evidence for the role of GABA in frontotemporal lobar degeneration came from confirmation that the effects of tiagabine on local circuits depended not only on participant group, but also on individual baseline GABA levels. Specifically, the phasic inhibition of deep cortico-cortical pyramidal neurons following tiagabine, but not placebo, was a function of GABA concentration. The study provides proof-of-concept for the potential of dynamic causal modelling to elucidate mechanisms of human neurodegenerative disease, and explains the variation in response to candidate therapies among patients. The laminar- and neurotransmitter-specific features of the modelling framework, can be used to study other treatment approaches and disorders. In the context of frontotemporal lobar degeneration, we suggest that neurophysiological restoration in selected patients, by targeting neurotransmitter deficits, could be used to bridge between clinical and preclinical models of disease, and inform the personalized selection of drugs and stratification of patients for future clinical trials.Wellcome TrustNational Institute for Health Research Cambridge Biomedical Research CentreMedical Research CouncilMedical Research CouncilMedical Research CouncilMedical Research CouncilCambridge Centre for Parkinson-plusAssociation of British NeurologistsHolt Fellowshi

Determinants of outcome in operatively and non-operatively treated Weber-B ankle fractures

Introduction: Treatment of ankle fractures is often based on fracture type and surgeon's individual judgment. Literature concerning the treatment options and outcome are dated and frequently contradicting. The aim of this study was to determine the clinical and functional outcome after AO-Weber B-type ankle fractures in operatively and conservatively treated patients and to determine which factors influenced outcome. Patients and methods: A retrospective cohort study in patients with a AO-Weber B-type ankle fracture. Patient, fracture and treatment characteristics were recorded. Clinical and functional outcome was measured using the Olerud-Molander Ankle Score (OMAS), the American Orthopaedic Foot and Ankle Society ankle-hindfoot score (AOFAS) and a Visual Analog Score (VAS) for overall satisfaction (range 0-10). Results: Eighty-two patients were treated conservatively and 103 underwent operative treatment. The majority was female. Most conservatively treated fractures were AO-Weber B1.1 type fractures. Fractures with fibular displacement (mainly AO type B1.2 and Lauge-Hansen type SER-4) were predominantly treated operatively. The outcome scores in the non-operative group were OMAS 93, AOFAS 98, and VAS 8. Outcome in this group was independently negatively affected by age, affected side, BMI, fibular displacement, and duration of plaster immobilization. In the surgically treated group, the OMAS, AOFAS, and VAS scores were 90, 97, and 8, respectively, with outcome negatively influenced by duration of plaster immobilization. Conclusion: Treatment selection based upon stability and surgeon's judgment led to overall good clinical outcome in both treatment groups. Reducing the cast immobilization period may further improve outcome

Production of medium-chain fatty acids and higher alcohols by a synthetic co-culture grown on carbon monoxide or syngas

Synthesis gas, a mixture of CO, H2, and CO2, is a promising renewable feedstock for bio-based production of organic chemicals. Production of medium-chain fatty acids can be performed via chain elongation, utilizing acetate and ethanol as main substrates. Acetate and ethanol are main products of syngas fermentation by acetogens. Therefore, syngas can be indirectly used as a substrate for the chain elongation process.ERC Grant (Project 323009) and the Gravitation Grant (Project 024.002.002) of the Netherlands Ministry of Education, Culture and Science, and the Netherlands Science Foundation (NWO