Clinical Applications of Stochastic Dynamic Models of the Brain, Part II: A Review

Brain activity derives from intrinsic dynamics (due to neurophysiology and anatomical connectivity) in concert with stochastic effects that arise from sensory fluctuations, brainstem discharges, and random microscopic states such as thermal noise. The dynamic evolution of systems composed of both dynamic and random fluctuations can be studied with stochastic dynamic models (SDMs). This article, Part II of a two-part series, reviews applications of SDMs to large-scale neural systems in health and disease. Stochastic models have already elucidated a number of pathophysiological phenomena, such as epilepsy and hypoxic ischemic encephalopathy, although their use in biological psychiatry remains rather nascent. Emerging research in this field includes phenomenological models of mood fluctuations in bipolar disorder and biophysical models of functional imaging data in psychotic and affective disorders. Together with deeper theoretical considerations, this work suggests that SDMs will play a unique and influential role in computational psychiatry, unifying empirical observations with models of perception and behavior

A Mechanism of Co-Existence of Bursting and Silent Regimes of Activities of a Neuron

The co-existence of bursting activity and silence is a common property of various neuronal models. We describe a novel mechanism explaining the co-existence of and the transition between these two regimes. It is based on the specific homoclinic and Andronov-Hopf bifurcations of the hyper- and depolarized steady states that determine the co-existence domain in the parameter space of the leech heart interneuron models: canonical and simplified. We found that a sub-critical Andronov-Hopf bifurcation of the hyperpolarized steady state gives rise to small amplitude sub-threshold oscillations terminating through the secondary homoclinic bifurcation. Near the corresponding boundary the system can exhibit long transition from bursting oscillations into silence, as well as the bi-stability where the observed regime is determined by the initial state of the neuron. The mechanism found is shown to be generic for the simplified 4D and the original 14D leech heart interneuron models

Synchronization of Coupled and Periodically Forced Chemical Oscillators

Physiological rhythms are essential in all living organisms. Such rhythms are regulated through the interactions of many cells. Deviation of a biological system from its normal rhythms can lead to physiological maladies. The tremor and symptoms associated with Parkinson\u27s disease are thought to emerge from abnormal synchrony of neuronal activity within the neural network of the brain. Deep brain stimulation is a therapeutic technique that can remove this pathological synchronization by the application of a periodic desynchronizing signal. Herein, we used the photosensitive Belousov--Zhabotinsky (BZ) chemical reaction to test the mechanism of deep brain stimulation. A collection of oscillators are initially synchronized using a regular light signal. Desynchronization is then attempted using an appropriately chosen desynchronizing signal based on information found in the phase response curve.;Coupled oscillators in various network topologies form the most common prototypical systems for studying networks of dynamical elements. In the present study, we couple discrete BZ photochemical oscillators in a network configuration. Different behaviors are observed on varying the coupling strength and the frequency heterogeneity, including incoherent oscillations to partial and full frequency entrainment. Phase clusters are organized symmetrically or non-symmetrically in phase-lag synchronization structures, a novel phase wave entrainment behavior in non-continuous media. The behavior is observed over a range of moderate coupling strengths and a broad frequency distribution of the oscillators

Using Phase Response Curves to Optimize Deep Brain Stimulation

University of Minnesota Ph.D. dissertation. April 2016. Major: Neuroscience. Advisor: Theoden Netoff. 1 computer file (PDF); vii, 190 pages.Deep brain stimulation (DBS) is a neuromodulation therapy effective at treating motor symptoms of patients with Parkinson’s disease (PD). Currently, an open-loop approach is used to set stimulus parameters, where stimulation settings are programmed by a clinician using a time intensive trial-and-error process. There is a need for a systematic approach to tuning stimulation parameters based on a patient’s physiology. An effective biomarker in the recorded neural signal is needed for this approach. It is hypothesized that DBS may work by disrupting enhanced oscillatory activity seen in PD. In this thesis I propose and provide evidence for using a simple measure, called a phase response curve, to systematically tune stimulation parameters and develop novel approaches to stimulation to suppress pathological oscillations. In this work I show that PRCs can be used to optimize stimulus frequency, waveform, and stimulus phase to disrupt a pathological oscillation in a computational model of Parkinson’s disease and/or to disrupt entrainment of single neurons in vitro. This approach has the potential to improve efficacy and reduce post-operative programming time

Synchronization in periodically driven and coupled stochastic systems-A discrete state approach

Wir untersuchen das Verhalten von stochastischen bistabilen und erregbaren Systemen auf der Basis einer Modellierung mit diskreten Zuständen. In Ergänzung zum bekannten Markovschen Zwei-Zustandsmodell bistabiler stochastischer Dynamik stellen wir ein nicht Markovsches Drei-Zustandsmodell für erregbare Systeme vor. Seine relative Einfachheit, verglichen mit stochastischen Modellen erregbarer Dynamik mit kontinuierlichem Phasenraum, ermöglicht eine teilweise analytische Auswertung in verschiedenen Zusammenhängen. Zunächst untersuchen wir den gemeinsamen Einfluß eines periodischen Treibens und Rauschens. Dieser wird entweder mit Hilfe spektraler Größen oder durch Synchronisation des Systems mit dem treibenden Signal charakterisiert. Wir leiten analytische Ausdrücke für die spektrale Leistungsverstärkung und das Signal-zu-Rauschen Verhältnis für periodisch getriebene Renewal-Prozesse her und wenden diese auf das diskrete Modell für erregbare Dynamik an. Stochastische Synchronization des Systems mit dem treibenden Signal wird auf der Basis der Diffusionseigenschaften der Übergangsereignisse zwischen den diskreten Zuständen untersucht. Wir leiten allgemeine Formeln her, um die mittlere Häufigkeit dieser Ereignisse sowie deren effektiven Diffusionskoeffizienten zu berechnen. Über die konkrete Anwendung auf die untersuchten diskreten Modelle hinaus stellen diese Ergebnisse ein neues Werkzeug für die Untersuchung periodischer Renewal-Prozesse dar. Schließlich betrachten wir noch das Verhalten global gekoppelter bistabiler und erregbarer Systeme. Im Gegensatz zu bistabilen System können erregbare Systeme synchronisiert werden und zeigen kohärente Oszillationen. Alle Untersuchungen des nicht Markovschen Drei-Zustandsmodells werden mit dem prototypischen Modell für erregbare Dynamik, dem FitzHugh-Nagumo System, verglichen und zeigen eine gute Übereinstimmung.We investigate the behavior of stochastic bistable and excitable dynamics based on a discrete state modeling. In addition to the well known Markovian two state model for bistable dynamics we introduce a non Markovian three state model for excitable systems. Its relative simplicity compared to stochastic models of excitable dynamics with continuous phase space allows to obtain analytical results in different contexts. First, we study the joint influence of periodic signals and noise, both based on a characterization in terms of spectral quantities and in terms of synchronization with the periodic driving. We present expressions for the spectral power amplification and signal to noise ratio for renewal processes driven by periodic signals and apply these results to the discrete model for excitable systems. Stochastic synchronization of the system to the driving signal is investigated based on diffusion properties of the transition events between the discrete states. We derive general results for the mean frequency and effective diffusion coefficient which, beyond the application to the discrete models considered in this work, provide a new tool in the study of periodically driven renewal processes. Finally the behavior of globally coupled excitable and bistable units is investigated based on the discrete state description. In contrast to the bistable systems, the excitable system exhibits synchronization and thus coherent oscillations. All investigations of the non Markovian three state model are compared with the prototypical continuous model for excitable dynamics, the FitzHugh-Nagumo system, revealing a good agreement between both models