Computational study of resting state network dynamics

Lo scopo di questa tesi è quello di mostrare, attraverso una simulazione con il software The Virtual Brain, le più importanti proprietà della dinamica cerebrale durante il resting state, ovvero quando non si è coinvolti in nessun compito preciso e non si è sottoposti a nessuno stimolo particolare. Si comincia con lo spiegare cos’è il resting state attraverso una breve revisione storica della sua scoperta, quindi si passano in rassegna alcuni metodi sperimentali utilizzati nell’analisi dell’attività cerebrale, per poi evidenziare la differenza tra connettività strutturale e funzionale. In seguito, si riassumono brevemente i concetti dei sistemi dinamici, teoria indispensabile per capire un sistema complesso come il cervello. Nel capitolo successivo, attraverso un approccio ‘bottom-up’, si illustrano sotto il profilo biologico le principali strutture del sistema nervoso, dal neurone alla corteccia cerebrale. Tutto ciò viene spiegato anche dal punto di vista dei sistemi dinamici, illustrando il pionieristico modello di Hodgkin-Huxley e poi il concetto di dinamica di popolazione. Dopo questa prima parte preliminare si entra nel dettaglio della simulazione. Prima di tutto si danno maggiori informazioni sul software The Virtual Brain, si definisce il modello di network del resting state utilizzato nella simulazione e si descrive il ‘connettoma’ adoperato. Successivamente vengono mostrati i risultati dell’analisi svolta sui dati ricavati, dai quali si mostra come la criticità e il rumore svolgano un ruolo chiave nell'emergenza di questa attività di fondo del cervello. Questi risultati vengono poi confrontati con le più importanti e recenti ricerche in questo ambito, le quali confermano i risultati del nostro lavoro. Infine, si riportano brevemente le conseguenze che porterebbe in campo medico e clinico una piena comprensione del fenomeno del resting state e la possibilità di virtualizzare l’attività cerebrale

Investigation of pattern generating mechanisms during atrial fibrillation based on the FitzHugh Nagumo equations

Die häufigste Arrhythmie des Herzens im klinischen Alltag ist Vorhofflimmern. Sie ist die Ursache von einem Drittel aller Behandlungen von Herzrhythmusstörungen. Obwohl das Phänomen des Vorhofflimmerns seit Anfang des letzten Jahrhunderts bekannt ist, sind die zugrunde liegenden Mechanismen noch nicht ausreichend verstanden. Als mögliche generierende Mechanismen werden in dieser Arbeit ektopische Zentren und Spiralwellen auf der Grundlage der FitzHugh-Nagumo- Gleichungen untersucht. Zur Darstellung von lokalen Gewebeveränderungen und der mit ihnen verbundenen Entstehung von ektopischen Zentren und Spiralwellen werden Zelleigenschaften wie die Anregbarkeit und die Stabilität des Ruhezustandes in räumlich begrenzten Gebieten variiert. Das Auftreten von Aktivitätsmustern in Abhängigkeit der linearen Ausdehnung der modifizierten Zellbereiche und der Stärke der Modifikation wird in dynamischen Phasendiagrammen erfasst und die mit den verschiedenen Mustern verbundenen Eigenschaften werden analysiert. Der abschließende Teil betrifft die Untersuchung von Mustern, welche durch Interferenz von regelmässigen, periodisch angeregten Wellen im rechten Vorhof mit Wellen ausgehend von einer stabilen Spiralwelle im linken Vorhof entstehen. Es wird gezeigt, dass diese Interferenz Ursache eines Flimmerzustandes im rechten Vorhof sein kann. Dabei führt insbesondere eine hohe Anregungsrate zu einem irregulären, flimmerähnlichen Zustand im rechten Vorhof. Sie erweist sich als Schlüsselfaktor für das Auftreten von Flimmerepisoden.Atrial fibrillation is the most important arrhythmia in clinical practice, accounting for one third of hospitalisations for cardiac disrhythms. Although it is known since the beginning of the last century, the underlying mechanisms are still under disucssion. In this work two proposed mechanisms are investigated, ectopic activity and spiral waves, with focus on their generating conditions, characteristic properties and wether they can be a possible cause of atrial fibrillation. Thereby, the cell properties like excitability and resting state stability are spatially varied to model possible generating conditions. The calculations are carried out on the basis of the FitzHugh Nagumo model. Dynamical phase diagrams are constructed for the ectopic activity as well as for the spiral waves, which classify the behaviour of the system in dependence on the properties of the spatial variation of the cell properties. The fibrillation rate is analysed and a transition from anatomical to functional reentry is observed for the spiral waves. Moreover, interference patterns of waves are studied in comparison to patterns found in recent experiments. The interference of waves from a stable spiral wave in the left atrium with regular paced waves in the right atrium, as a model of the sinus node, is shown to be a possible cause of fibrillation in the right atrium. A high pacing rate can yield an irregular, fibrillatory state, which describes the generation of fibrillation episodes and is seen as a key factor for the occurrence of fibrillation episodes.Ilmenau, Techn. Univ., Diplomarbeit, 200

Complex Dynamics in Dedicated / Multifunctional Neural Networks and Chaotic Nonlinear Systems

We study complex behaviors arising in neuroscience and other nonlinear systems by combining dynamical systems analysis with modern computational approaches including GPU parallelization and unsupervised machine learning. To gain insights into the behaviors of brain networks and complex central pattern generators (CPGs), it is important to understand the dynamical principles regulating individual neurons as well as the basic structural and functional building blocks of neural networks. In the first section, we discuss how symbolic methods can help us analyze neural dynamics such as bursting, tonic spiking and chaotic mixed-mode oscillations in various models of individual neurons, the bifurcations that underlie transitions between activity types, as well as emergent network phenomena through synergistic interactions seen in realistic neural circuits, such as network bursting from non-intrinsic bursters. The second section is focused on the origin and coexistence of multistable rhythms in oscillatory neural networks of inhibitory coupled cells. We discuss how network connectivity and intrinsic properties of the cells affect the dynamics, and how even simple circuits can exhibit a variety of mono/multi-stable rhythms including pacemakers, half-center oscillators, multiple traveling-waves, fully synchronous states, as well as various chimeras. Our analyses can help generate verifiable hypotheses for neurophysiological experiments on central pattern generators. In the last section, we demonstrate the inter-disciplinary nature of this research through the applications of these techniques to identify the universal principles governing both simple and complex dynamics, and chaotic structure in diverse nonlinear systems. Using a classical example from nonlinear laser optics, we elaborate on the multiplicity and self-similarity of key organizing structures in 2D parameter space such as homoclinic and heteroclinic bifurcation curves, Bykov T-point spirals, and inclination flips. This is followed by detailed computational reconstructions of the spatial organization and 3D embedding of bifurcation surfaces, parametric saddles, and isolated closed curves (isolas). The generality of our modeling approaches could lead to novel methodologies and nonlinear science applications in biological, medical and engineering systems

Capture of fixation by rotational flow; a deterministic hypothesis regarding scaling and stochasticity in fixational eye movements.

Visual scan paths exhibit complex, stochastic dynamics. Even during visual fixation, the eye is in constant motion. Fixational drift and tremor are thought to reflect fluctuations in the persistent neural activity of neural integrators in the oculomotor brainstem, which integrate sequences of transient saccadic velocity signals into a short term memory of eye position. Despite intensive research and much progress, the precise mechanisms by which oculomotor posture is maintained remain elusive. Drift exhibits a stochastic statistical profile which has been modeled using random walk formalisms. Tremor is widely dismissed as noise. Here we focus on the dynamical profile of fixational tremor, and argue that tremor may be a signal which usefully reflects the workings of oculomotor postural control. We identify signatures reminiscent of a certain flavor of transient neurodynamics; toric traveling waves which rotate around a central phase singularity. Spiral waves play an organizational role in dynamical systems at many scales throughout nature, though their potential functional role in brain activity remains a matter of educated speculation. Spiral waves have a repertoire of functionally interesting dynamical properties, including persistence, which suggest that they could in theory contribute to persistent neural activity in the oculomotor postural control system. Whilst speculative, the singularity hypothesis of oculomotor postural control implies testable predictions, and could provide the beginnings of an integrated dynamical framework for eye movements across scales

Dynamics and precursor signs for phase transitions in neural systems

This thesis investigates neural state transitions associated with sleep, seizure and anaesthesia. The aim is to address the question: How does a brain traverse the critical threshold between distinct cortical states, both healthy and pathological? Specifically we are interested in sub-threshold neural behaviour immediately prior to state transition. We use theoretical neural modelling (single spiking neurons, a network of these, and a mean-field continuum limit) and in vitro experiments to address this question. Dynamically realistic equations of motion for thalamic relay neuron, reticular nuclei, cortical pyramidal and cortical interneuron in different vigilance states are developed, based on the Izhikevich spiking neuron model. A network of cortical neurons is assembled to examine the behaviour of the gamma-producing cortical network and its transition to lower frequencies due to effect of anaesthesia. Then a three-neuron model for the thalamocortical loop for sleep spindles is presented. Numerical simulations of these networks confirms spiking consistent with reported in vivo measurement results, and provides supporting evidence for precursor indicators of imminent phase transition due to occurrence of individual spindles. To complement the spiking neuron networks, we study the Wilson–Cowan neural mass equations describing homogeneous cortical columns and a 1D spatial cluster of such columns. The abstract representation of cortical tissue by a pair of coupled integro-differential equations permits thorough linear stability, phase plane and bifurcation analyses. This model shows a rich set of spatial and temporal bifurcations marking the boundary to state transitions: saddle-node, Hopf, Turing, and mixed Hopf–Turing. Close to state transition, white-noise-induced subthreshold fluctuations show clear signs of critical slowing down with prolongation and strengthening of autocorrelations, both in time and space, irrespective of bifurcation type. Attempts at in vitro capture of these predicted leading indicators form the last part of the thesis. We recorded local field potentials (LFPs) from cortical and hippocampal slices of mouse brain. State transition is marked by the emergence and cessation of spontaneous seizure-like events (SLEs) induced by bathing the slices in an artificial cerebral spinal fluid containing no magnesium ions. Phase-plane analysis of the LFP time-series suggests that distinct bifurcation classes can be responsible for state change to seizure. Increased variance and growth of spectral power at low frequencies (f < 15 Hz) was observed in LFP recordings prior to initiation of some SLEs. In addition we demonstrated prolongation of electrically evoked potentials in cortical tissue, while forwarding the slice to a seizing regime. The results offer the possibility of capturing leading temporal indicators prior to seizure generation, with potential consequences for understanding epileptogenesis. Guided by dynamical systems theory this thesis captures evidence for precursor signs of phase transitions in neural systems using mathematical and computer-based modelling as well as in vitro experiments

Dynamical principles in neuroscience

Dynamical modeling of neural systems and brain functions has a history of success over the last half century. This includes, for example, the explanation and prediction of some features of neural rhythmic behaviors. Many interesting dynamical models of learning and memory based on physiological experiments have been suggested over the last two decades. Dynamical models even of consciousness now exist. Usually these models and results are based on traditional approaches and paradigms of nonlinear dynamics including dynamical chaos. Neural systems are, however, an unusual subject for nonlinear dynamics for several reasons: (i) Even the simplest neural network, with only a few neurons and synaptic connections, has an enormous number of variables and control parameters. These make neural systems adaptive and flexible, and are critical to their biological function. (ii) In contrast to traditional physical systems described by well-known basic principles, first principles governing the dynamics of neural systems are unknown. (iii) Many different neural systems exhibit similar dynamics despite having different architectures and different levels of complexity. (iv) The network architecture and connection strengths are usually not known in detail and therefore the dynamical analysis must, in some sense, be probabilistic. (v) Since nervous systems are able to organize behavior based on sensory inputs, the dynamical modeling of these systems has to explain the transformation of temporal information into combinatorial or combinatorial-temporal codes, and vice versa, for memory and recognition. In this review these problems are discussed in the context of addressing the stimulating questions: What can neuroscience learn from nonlinear dynamics, and what can nonlinear dynamics learn from neuroscience?This work was supported by NSF Grant No. NSF/EIA-0130708, and Grant No. PHY 0414174; NIH Grant No. 1 R01 NS50945 and Grant No. NS40110; MEC BFI2003-07276, and Fundación BBVA

Mathematical methods of factorization and a feedback approach for biological systems

The first part of the thesis is devoted to factorizations of linear and nonlinear differential equations leading to solutions of the kink type. The second part contains a study of the synchronization of the chaotic dynamics of two Hodgkin-Huxley neurons by means of the mathematical tools belonging to the geometrical control theory.Comment: Ph. D. Thesis at IPICyT, San Luis Potosi, Mexico, 102 pp, 40 figs. Supervisors: Dr. H.C. Rosu and Dr. R. Fema

Mathematical frameworks for oscillatory network dynamics in neuroscience

The tools of weakly coupled phase oscillator theory have had a profound impact on the neuroscience community, providing insight into a variety of network behaviours ranging from central pattern generation to synchronisation, as well as predicting novel network states such as chimeras. However, there are many instances where this theory is expected to break down, say in the presence of strong coupling, or must be carefully interpreted, as in the presence of stochastic forcing. There are also surprises in the dynamical complexity of the attractors that can robustly appear—for example, heteroclinic network attractors. In this review we present a set of mathemat- ical tools that are suitable for addressing the dynamics of oscillatory neural networks, broadening from a standard phase oscillator perspective to provide a practical frame- work for further successful applications of mathematics to understanding network dynamics in neuroscience