Gene expression rearrangements denoting changes in the biological state

In many situations, the gene expression signature is a unique marker of the biological state. We study the modification of the gene expression distribution function when the biological state of a system experiences a change. This change may be the result of a selective pressure, as in the Long Term Evolution Experiment with E. Coli populations, or the progression to Alzheimer disease in aged brains, or the progression from a normal tissue to the cancer state. The first two cases seem to belong to a class of transitions, where the initial and final states are relatively close to each other, and the distribution function for the differential expressions is short ranged, with a tail of only a few dozens of strongly varying genes. In the latter case, cancer, the initial and final states are far apart and separated by a low-fitness barrier. The distribution function shows a very heavy tail, with thousands of silenced and over-expressed genes. We characterize the biological states by means of their principal component representations, and the expression distribution functions by their maximal and minimal differential expression values and the exponents of the Pareto laws describing the tails

Tensor Analysis and Fusion of Multimodal Brain Images

Current high-throughput data acquisition technologies probe dynamical systems with different imaging modalities, generating massive data sets at different spatial and temporal resolutions posing challenging problems in multimodal data fusion. A case in point is the attempt to parse out the brain structures and networks that underpin human cognitive processes by analysis of different neuroimaging modalities (functional MRI, EEG, NIRS etc.). We emphasize that the multimodal, multi-scale nature of neuroimaging data is well reflected by a multi-way (tensor) structure where the underlying processes can be summarized by a relatively small number of components or "atoms". We introduce Markov-Penrose diagrams - an integration of Bayesian DAG and tensor network notation in order to analyze these models. These diagrams not only clarify matrix and tensor EEG and fMRI time/frequency analysis and inverse problems, but also help understand multimodal fusion via Multiway Partial Least Squares and Coupled Matrix-Tensor Factorization. We show here, for the first time, that Granger causal analysis of brain networks is a tensor regression problem, thus allowing the atomic decomposition of brain networks. Analysis of EEG and fMRI recordings shows the potential of the methods and suggests their use in other scientific domains.Comment: 23 pages, 15 figures, submitted to Proceedings of the IEE

Critical comments on EEG sensor space dynamical connectivity analysis

Many different analysis techniques have been developed and applied to EEG recordings that allow one to investigate how different brain areas interact. One particular class of methods, based on the linear parametric representation of multiple interacting time series, is widely used to study causal connectivity in the brain. However, the results obtained by these methods should be interpreted with great care. The goal of this paper is to show, both theoretically and using simulations, that results obtained by applying causal connectivity measures on the sensor (scalp) time series do not allow interpretation in terms of interacting brain sources. This is because 1) the channel locations cannot be seen as an approximation of a source's anatomical location and 2) spurious connectivity can occur between sensors. Although many measures of causal connectivity derived from EEG sensor time series are affected by the latter, here we will focus on the well-known time domain index of Granger causality (GC) and on the frequency domain directed transfer function (DTF). Using the state-space framework and designing two simulation studies we show that mixing effects caused by volume conduction can lead to spurious connections, detected either by time domain GC or by DTF. Therefore, GC/DTF causal connectivity measures should be computed at the source level, or derived within analysis frameworks that model the effects of volume conduction. Since mixing effects can also occur in the source space, it is advised to combine source space analysis with connectivity measures that are robust to mixing

New Endovascular Method for Transvascular Exit of Arteries and Veins: Developed in Simulator, in Rat and in Rabbit with Full Clinical Integration

BACKGROUND: Endovascular technique has benefits vis-a-vis surgical access to organs with less accessible anatomical locations. To minimize surgical risk we propose a novel endovascular technique, to create parenchymal access through endovascular methods. METHODOLOGY/PRINCIPAL FINDINGS: We have developed, manufactured and tested an endovascular catheter with a depth limiting collar and a penetrating tip that is used to perforate vessels, thereby creating a working channel to the extra-vascular space. Computer simulations and subsequent interventions have been performed ex vivo and in vivo in both small and large animals by testing different prototypes. All tests were designed for testing extravascular hemostasis and absence of thrombo-embolic complications when exiting the vessels from the inside to the extra vascular space. We have deposited prototypes after intervention in vascular walls over a period of 14 days in rat with no impairment on blood flow and no signs of thrombo-embolic complications upon re-exploration (n = 7). We have also incorporated the catheter system with clinically available systems both in an ex vivo simulator setting and in a full scale clinical angiographical setting in rabbit were no bleeding (0%) in any of the interventions performed (n = 40). To prevent hemorrhage during termination of the procedure, a hollow electrolysis detachment-zone leaves the distal tip in the vessel-wall after the intervention. This has also been tested with absolute hemostasis in large animals (n = 6). CONCLUSIONS/SIGNIFICANCE: We have developed and tested a new system for transvascular tissue access in simulations, ex vivo and in vivo in small and large animals, integrating it with standard clinical catheters and angiographical environment, with absolute hemostasis and without thromboembolic complications. In a clinical setting for stem cell transplantation, local substance administration or tissue sampling, the benefit should be greatest in organs that are difficult or high-risk to access with other techniques, such as the pancreas, the central nervous system (CNS) and the heart

Neural Connectivity with Hidden Gaussian Graphical State-Model

The noninvasive procedures for neural connectivity are under questioning. Theoretical models sustain that the electromagnetic field registered at external sensors is elicited by currents at neural space. Nevertheless, what we observe at the sensor space is a superposition of projected fields, from the whole gray-matter. This is the reason for a major pitfall of noninvasive Electrophysiology methods: distorted reconstruction of neural activity and its connectivity or leakage. It has been proven that current methods produce incorrect connectomes. Somewhat related to the incorrect connectivity modelling, they disregard either Systems Theory and Bayesian Information Theory. We introduce a new formalism that attains for it, Hidden Gaussian Graphical State-Model (HIGGS). A neural Gaussian Graphical Model (GGM) hidden by the observation equation of Magneto-encephalographic (MEEG) signals. HIGGS is equivalent to a frequency domain Linear State Space Model (LSSM) but with sparse connectivity prior. The mathematical contribution here is the theory for high-dimensional and frequency-domain HIGGS solvers. We demonstrate that HIGGS can attenuate the leakage effect in the most critical case: the distortion EEG signal due to head volume conduction heterogeneities. Its application in EEG is illustrated with retrieved connectivity patterns from human Steady State Visual Evoked Potentials (SSVEP). We provide for the first time confirmatory evidence for noninvasive procedures of neural connectivity: concurrent EEG and Electrocorticography (ECoG) recordings on monkey. Open source packages are freely available online, to reproduce the results presented in this paper and to analyze external MEEG databases

S-cone signals invisible to the motion system can improve motion extraction via grouping by color

Peer reviewedPublisher PD

A Functional MRI and Magneto/Electro Source Imaging Procedure for Cognitive and Pre-surgical Evaluation

AbstractAnalysis of normal/pathological brain activity using neuroimaging methods is necessary to avoid operation risks, and the outcome serves as prior information for surgical neuronavigation. We present an fMRI/MEG/EEG-based methodology for tasks demanding mainly sensorimotor and visual/cognitive responses. This consists of carefully selected/designed stimulation paradigms and statistical parametric mapping methods that demonstrate the practicability of these techniques for clinical applications. The results replicate known findings in the brain-imaging field, with the improvement that our analyses are restricted to grey matter tissue. The latter enhance computations, which is advantageous for the massive data analyses that are typical of clinical and radiological functional brain “checkup” services