Temporally correlated fluctuations drive epileptiform dynamics

Published onlineJournal ArticleMacroscopic models of brain networks typically incorporate assumptions regarding the characteristics of afferent noise, which is used to represent input from distal brain regions or ongoing fluctuations in non-modelled parts of the brain. Such inputs are often modelled by Gaussian white noise which has a flat power spectrum. In contrast, macroscopic fluctuations in the brain typically follow a 1/f(b) spectrum. It is therefore important to understand the effect on brain dynamics of deviations from the assumption of white noise. In particular, we wish to understand the role that noise might play in eliciting aberrant rhythms in the epileptic brain. To address this question we study the response of a neural mass model to driving by stochastic, temporally correlated input. We characterise the model in terms of whether it generates "healthy" or "epileptiform" dynamics and observe which of these dynamics predominate under different choices of temporal correlation and amplitude of an Ornstein-Uhlenbeck process. We find that certain temporal correlations are prone to eliciting epileptiform dynamics, and that these correlations produce noise with maximal power in the δ and θ bands. Crucially, these are rhythms that are found to be enhanced prior to seizures in humans and animal models of epilepsy. In order to understand why these rhythms can generate epileptiform dynamics, we analyse the response of the model to sinusoidal driving and explain how the bifurcation structure of the model gives rise to these findings. Our results provide insight into how ongoing fluctuations in brain dynamics can facilitate the onset and propagation of epileptiform rhythms in brain networks. Furthermore, we highlight the need to combine large-scale models with noise of a variety of different types in order to understand brain (dys-)function.This work was supported by the European Commission through the FP7 Marie Curie Initial Training Network 289146 (NETT: Neural Engineering Transformative Technologies), by the Spanish Ministry of Economy and Competitiveness and FEDER (project FIS2012-37655-C02-01). J.G.O. also acknowledges support from the ICREA Academia programme, the Generalitat de Catalunya (project 2014SGR0947), and the “María de Maeztu” Programme for Units of Excellence in R&D (Spanish Ministry of Economy and Competitiveness, MDM-2014-0370) M.G. gratefully acknowledges the financial support of the EPSRC via grant EP/N014391/1. The contribution of M.G. was generously supported by a Wellcome Trust Institutional Strategic Support Award (WT105618MA)

Where Have All the Interactions Gone? Estimating the Coverage of Two-Hybrid Protein Interaction Maps

Yeast two-hybrid screens are an important method for mapping pairwise physical interactions between proteins. The fraction of interactions detected in independent screens can be very small, and an outstanding challenge is to determine the reason for the low overlap. Low overlap can arise from either a high false-discovery rate (interaction sets have low overlap because each set is contaminated by a large number of stochastic false-positive interactions) or a high false-negative rate (interaction sets have low overlap because each misses many true interactions). We extend capture–recapture theory to provide the first unified model for false-positive and false-negative rates for two-hybrid screens. Analysis of yeast, worm, and fly data indicates that 25% to 45% of the reported interactions are likely false positives. Membrane proteins have higher false-discovery rates on average, and signal transduction proteins have lower rates. The overall false-negative rate ranges from 75% for worm to 90% for fly, which arises from a roughly 50% false-negative rate due to statistical undersampling and a 55% to 85% false-negative rate due to proteins that appear to be systematically lost from the assays. Finally, statistical model selection conclusively rejects the Erdös-Rényi network model in favor of the power law model for yeast and the truncated power law for worm and fly degree distributions. Much as genome sequencing coverage estimates were essential for planning the human genome sequencing project, the coverage estimates developed here will be valuable for guiding future proteomic screens. All software and datasets are available in Datasets S1 and S2, Figures S1–S5, and Tables S1−S6, and are also available from our Web site, http://www.baderzone.org

Learning nonparametric ordinary differential equations from noisy data

Learning nonparametric systems of Ordinary Differential Equations (ODEs) dot x = f(t,x) from noisy data is an emerging machine learning topic. We use the well-developed theory of Reproducing Kernel Hilbert Spaces (RKHS) to define candidates for f for which the solution of the ODE exists and is unique. Learning f consists of solving a constrained optimization problem in an RKHS. We propose a penalty method that iteratively uses the Representer theorem and Euler approximations to provide a numerical solution. We prove a generalization bound for the L2 distance between x and its estimator and provide experimental comparisons with the state-of-the-art.Comment: 25 pages, 6 figure

Intensity Inhomogeneity Correction of SD-OCT Data Using Macular Flatspace

Images of the retina acquired using optical coherence tomography (OCT) often suffer from intensity inhomogeneity problems that degrade both the quality of the images and the performance of automated algorithms utilized to measure structural changes. This intensity variation has many causes, including off-axis acquisition, signal attenuation, multi-frame averaging, and vignetting, making it difficult to correct the data in a fundamental way. This paper presents a method for inhomogeneity correction by acting to reduce the variability of intensities within each layer. In particular, the N3 algorithm, which is popular in neuroimage analysis, is adapted to work for OCT data. N3 works by sharpening the intensity histogram, which reduces the variation of intensities within different classes. To apply it here, the data are first converted to a standardized space called macular flat space (MFS). MFS allows the intensities within each layer to be more easily normalized by removing the natural curvature of the retina. N3 is then run on the MFS data using a modified smoothing model, which improves the efficiency of the original algorithm. We show that our method more accurately corrects gain fields on synthetic OCT data when compared to running N3 on non-flattened data. It also reduces the overall variability of the intensities within each layer, without sacrificing contrast between layers, and improves the performance of registration between OCT images

Associations Between Performance on an Abbreviated CogState Battery, Other Measures of Cognitive Function, and Biomarkers in People at Risk for Alzheimer\u27s Disease

It is not known whether computerized cognitive assessments, like the CogState battery, are sensitive to preclinical cognitive changes or pathology in people at risk for Alzheimer\u27s disease(AD). In 469 late middle-aged participants from the Wisconsin Registry for Alzheimer\u27s Prevention(mean age 63.8±7 years at testing; 67% female; 39% APOE4+), we examined relationships between a CogState abbreviated battery(CAB) of seven tests and demographic characteristics, traditional paper-based neuropsychological tests as well as a composite cognitive impairment index, cognitive impairment status(determined by consensus review), and biomarkers for amyloid and tau(CSF phosphorylated-tau/Aβ42 and global PET-PiB burden) and neural injury(CSF neurofilament light protein). CSF and PET-PiB were collected in n = 71 and n = 91 participants, respectively, approximately four years prior to CAB testing. For comparison, we examined three traditional tests of delayed memory in parallel. Similar to studies in older samples, the CAB was less influenced by demographic factors than traditional tests. CAB tests were generally correlated with most paper-based cognitive tests examined and mapped onto the same cognitive domains. Greater composite cognitive impairment index was associated with worse performance on all CAB tests. Cognitively impaired participants performed significantly worse compared to normal controls on all but one CAB test. Poorer One Card Learning test performance was associated with higher levels of CSF phosphorylated-tau/Aβ42. These results support the use of the CogState battery as measures of early cognitive impairment in studies of people at risk for AD

Back to the Eneolithic: Exploring the Rudki-type ornaments from Poland

For a long time, the Eneolithic attribution of the Rudki-type double spiral ornaments was contested by a wide academic audience, and therefore, this new and extraordinary category of the copper metalwork seemed to have fallen into scientific oblivion. In this paper, we contribute to the debate about cultural attribution of the Rudki-type double spiral ornaments considering their chemical and isotope characteristics (using ED XRF and MC-ICP-MS) and the manufacturing technology (OM, X-ray, CT). Noticeably, this study represents the first documented implementation of the lead isotope analysis (LIA) for the Eneolithic metalwork from Poland. The new scientific analyses give ground to the hypothesis that the Rudki-type double spiral ornaments were produced by the Baden culture metalworker(s) who practiced somewhere in the Carpathian Basin and who have used copper ore mined in the Slovak Ore Mountains (Spania Dolina-Banska Bystrica-Kremnica mine complex). These ornaments were redistributed towards the northern ecumene of the Baden culture complex. The new owners, the Funnel Beaker (TRB) culture communities from the region of modern Poland, deposited the ornaments in hoards (Kaldus, Przeuszyn and Rudki) during the mid-4th millennium BC. The results, furthermore, indicate that the so-called Baden spiral metalwork package must be now complemented by the Rudki-type double spiral ornaments. Remarkably, this package also found an echo in pottery decoration, as documented by a narrative scene incised on an amphora from Kaldus, which could be also interpreted as one of the earliest known proofs for the wagon transport in Europe, alongside the famous ones reported from Bronocice or Flintbek.Material Culture Studie