Towards dynamical network biomarkers in neuromodulation of episodic migraine

Computational methods have complemented experimental and clinical neursciences and led to improvements in our understanding of the nervous systems in health and disease. In parallel, neuromodulation in form of electric and magnetic stimulation is gaining increasing acceptance in chronic and intractable diseases. In this paper, we firstly explore the relevant state of the art in fusion of both developments towards translational computational neuroscience. Then, we propose a strategy to employ the new theoretical concept of dynamical network biomarkers (DNB) in episodic manifestations of chronic disorders. In particular, as a first example, we introduce the use of computational models in migraine and illustrate on the basis of this example the potential of DNB as early-warning signals for neuromodulation in episodic migraine.Comment: 13 pages, 5 figure

Data clustering using a model granular magnet

We present a new approach to clustering, based on the physical properties of an inhomogeneous ferromagnet. No assumption is made regarding the underlying distribution of the data. We assign a Potts spin to each data point and introduce an interaction between neighboring points, whose strength is a decreasing function of the distance between the neighbors. This magnetic system exhibits three phases. At very low temperatures it is completely ordered; all spins are aligned. At very high temperatures the system does not exhibit any ordering and in an intermediate regime clusters of relatively strongly coupled spins become ordered, whereas different clusters remain uncorrelated. This intermediate phase is identified by a jump in the order parameters. The spin-spin correlation function is used to partition the spins and the corresponding data points into clusters. We demonstrate on three synthetic and three real data sets how the method works. Detailed comparison to the performance of other techniques clearly indicates the relative success of our method.Comment: 46 pages, postscript, 15 ps figures include

EEG dynamical network analysis method reveals the neural signature of visual-motor coordination

Human visual-motor coordination is an essential function of movement control, which requires interactions of multiple brain regions. Understanding the cortical-motor coordination is important for improving physical therapy for motor disabilities. However, its underlying transient neural dynamics is still largely unknown. In this study, we applied an eigenvector-based dynamical network analysis method to investigate the functional connectivity calculated from electroencephalography (EEG) signals under visual-motor coordination task and to identify its meta-stable states dynamics. We first tested this signal processing on a simulated network to evaluate it in comparison with other dynamical methods, demonstrating that the eigenvector-based dynamical network analysis was able to correctly extract the dynamical features of the evolving networks. Subsequently, the eigenvector-based analysis was applied to EEG data collected under a visual-motor coordination experiment. In the EEG study with participants, the results of both topological analysis and the eigenvector-based dynamical analysis were able to distinguish different experimental conditions of visual tracking task. With the dynamical analysis, we showed that different visual-motor coordination states can be distinguished by investigating the meta-stable states dynamics of the functional connectivity

The ecology of suffering: developmental disorders of structured stress, emotion, and chronic inflammation

'Punctuated equilibrium' models of cognitive process, adapted from the Large Deviations Program of probability theory, are applied to the interaction between immune function and emotion in the context of culturally structured psychosocial stress. The analysis suggests: (1) Chronic inflammatory diseases should be comorbid and synergistic with characteristic emotional dysfunction, and may form a collection of joint disorders most effectively treated at the individual level using multifactorial 'mind/body' strategies. (2) Culturally constructed psychosocial stress can literally write an image of itself onto the punctuated etiology and progression of such composite disorders, beginning a trajectory to disease in utero or early childhood, and continuing throughout the life course, suggesting that, when moderated by 'social exposures', these are developmental disorders. (3) At the community level of organization, strategies for prevention and control of the spectrum of emotional/inflammatory developmental disorders must include redress of cross-sectional and logitudinal (i.e. historical) patterns of inequality and injustice which generate structured psychosocial stress. Evidence further suggests that within 'Westernized' or 'market economy' societies, such stress will inevitably entrain high as well as lower stutus subopulations into a unified ecology of suffering

Machine learning and its applications in reliability analysis systems

In this thesis, we are interested in exploring some aspects of Machine Learning (ML) and its application in the Reliability Analysis systems (RAs). We begin by investigating some ML paradigms and their- techniques, go on to discuss the possible applications of ML in improving RAs performance, and lastly give guidelines of the architecture of learning RAs. Our survey of ML covers both levels of Neural Network learning and Symbolic learning. In symbolic process learning, five types of learning and their applications are discussed: rote learning, learning from instruction, learning from analogy, learning from examples, and learning from observation and discovery. The Reliability Analysis systems (RAs) presented in this thesis are mainly designed for maintaining plant safety supported by two functions: risk analysis function, i.e., failure mode effect analysis (FMEA) ; and diagnosis function, i.e., real-time fault location (RTFL). Three approaches have been discussed in creating the RAs. According to the result of our survey, we suggest currently the best design of RAs is to embed model-based RAs, i.e., MORA (as software) in a neural network based computer system (as hardware). However, there are still some improvement which can be made through the applications of Machine Learning. By implanting the 'learning element', the MORA will become learning MORA (La MORA) system, a learning Reliability Analysis system with the power of automatic knowledge acquisition and inconsistency checking, and more. To conclude our thesis, we propose an architecture of La MORA

Flipping Biological Switches: Solving for Optimal Control: A Dissertation

Switches play an important regulatory role at all levels of biology, from molecular switches triggering signaling cascades to cellular switches regulating cell maturation and apoptosis. Medical therapies are often designed to toggle a system from one state to another, achieving a specified health outcome. For instance, small doses of subpathologic viruses activate the immune system’s production of antibodies. Electrical stimulation revert cardiac arrhythmias back to normal sinus rhythm. In all of these examples, a major challenge is finding the optimal stimulus waveform necessary to cause the switch to flip. This thesis develops, validates, and applies a novel model-independent stochastic algorithm, the Extrema Distortion Algorithm (EDA), towards finding the optimal stimulus. We validate the EDA’s performance for the Hodgkin-Huxley model (an empirically validated ionic model of neuronal excitability), the FitzHugh-Nagumo model (an abstract model applied to a wide range of biological systems that that exhibit an oscillatory state and a quiescent state), and the genetic toggle switch (a model of bistable gene expression). We show that the EDA is able to not only find the optimal solution, but also in some cases excel beyond the traditional analytic approaches. Finally, we have computed novel optimal stimulus waveforms for aborting epileptic seizures using the EDA in cellular and network models of epilepsy. This work represents a first step in developing a new class of adaptive algorithms and devices that flip biological switches, revealing basic mechanistic insights and therapeutic applications for a broad range of disorders