Depolarization block in olfactory sensory neurons expands the dimensionality of odor encoding.

Upon strong and prolonged excitation, neurons can undergo a silent state called depolarization block that is often associated with disorders such as epileptic seizures. Here, we show that neurons in the peripheral olfactory system undergo depolarization block as part of their normal physiological function. Typically, olfactory sensory neurons enter depolarization block at odor concentrations three orders of magnitude above their detection threshold, thereby defining receptive fields over concentration bands.

Leveraging deep learning to control neural oscillators.

Modulation of the firing times of neural oscillators has long been an important control objective, with applications including Parkinson's disease, Tourette's syndrome, epilepsy, and learning. One common goal for such modulation is desynchronization, wherein two or more oscillators are stimulated to transition from firing in phase with each other to firing out of phase. The optimization of such stimuli has been well studied, but this typically relies on either a reduction of the dimensionality of the system or complete knowledge of the parameters and state of the system.

Analysis of neural clusters due to deep brain stimulation pulses.

Deep brain stimulation (DBS) is an established method for treating pathological conditions such as Parkinson's disease, dystonia, Tourette syndrome, and essential tremor. While the precise mechanisms which underly the effectiveness of DBS are not fully understood, several theoretical studies of populations of neural oscillators stimulated by periodic pulses have suggested that this may be related to clustering, in which subpopulations of the neurons are synchronized, but the subpopulations are desynchronized with respect to each other. The details of the clustering behavior depend on the frequency and amplitude of the stimulation in a complicated way.

Synchronization of heterogeneous oscillator populations in response to weak and strong coupling.

Synchronous behavior of a population of chemical oscillators is analyzed in the presence of both weak and strong coupling. In each case, we derive upper bounds on the critical coupling strength which are valid for arbitrary populations of nonlinear, heterogeneous oscillators. For weak perturbations, infinitesimal phase response curves are used to characterize the response to coupling, and graph theoretical techniques are used to predict synchronization.

Phase reduction and phase-based optimal control for biological systems: a tutorial.

A powerful technique for the analysis of nonlinear oscillators is the rigorous reduction to phase models, with a single variable describing the phase of the oscillation with respect to some reference state. An analog to phase reduction has recently been proposed for systems with a stable fixed point, and phase reduction for periodic orbits has recently been extended to take into account transverse directions and higher-order terms. This tutorial gives a unified treatment of such phase reduction techniques and illustrates their use through mathematical and biological examples.

Optimal phase control of biological oscillators using augmented phase reduction.

We develop a novel optimal control algorithm to change the phase of an oscillator using a minimum energy input, which also minimizes the oscillator's transversal distance to the uncontrolled periodic orbit. Our algorithm uses a two-dimensional reduction technique based on both isochrons and isostables. We develop a novel method to eliminate cardiac alternans by connecting our control algorithm with the underlying physiological problem.

Phase model-based neuron stabilization into arbitrary clusters.

Deep brain stimulation (DBS) is a common method of combating pathological conditions associated with Parkinson's disease, Tourette syndrome, essential tremor, and other disorders, but whose mechanisms are not fully understood. One hypothesis, supported experimentally, is that some symptoms of these disorders are associated with pathological synchronization of neurons in the basal ganglia and thalamus. For this reason, there has been interest in recent years in finding efficient ways to desynchronize neurons that are both fast-acting and low-power.

Isostable reduction of periodic orbits.

The well-established method of phase reduction neglects information about a limit-cycle oscillator's approach towards its periodic orbit. Consequently, phase reduction suffers in practicality unless the magnitude of the Floquet multipliers of the underlying limit cycle are small in magnitude. By defining isostable coordinates of a periodic orbit, we present an augmentation to classical phase reduction which obviates this restriction on the Floquet multipliers.

Isostable reduction with applications to time-dependent partial differential equations.

Isostables and isostable reduction, analogous to isochrons and phase reduction for oscillatory systems, are useful in the study of nonlinear equations which asymptotically approach a stationary solution. In this work, we present a general method for isostable reduction of partial differential equations, with the potential power to reduce the dimensionality of a nonlinear system from infinity to 1. We illustrate the utility of this reduction by applying it to two different models with biological relevance.

Phasic Burst Stimulation: A Closed-Loop Approach to Tuning Deep Brain Stimulation Parameters for Parkinson's Disease.

We propose a novel, closed-loop approach to tuning deep brain stimulation (DBS) for Parkinson's disease (PD). The approach, termed Phasic Burst Stimulation (PhaBS), applies a burst of stimulus pulses over a range of phases predicted to disrupt pathological oscillations seen in PD. Stimulation parameters are optimized based on phase response curves (PRCs), which would be measured from each patient.

Toward a More Efficient Implementation of Antifibrillation Pacing.

We devise a methodology to determine an optimal pattern of inputs to synchronize firing patterns of cardiac cells which only requires the ability to measure action potential durations in individual cells. In numerical bidomain simulations, the resulting synchronizing inputs are shown to terminate spiral waves with a higher probability than comparable inputs that do not synchronize the cells as strongly. These results suggest that designing stimuli which promote synchronization in cardiac tissue could improve the success rate of defibrillation, and point towards novel strategies for optimizing antifibrillation pacing.

Dynamic analysis of a buckled asymmetric piezoelectric beam for energy harvesting.

A model of a buckled beam energy harvester is analyzed to determine the phenomena behind the transition between high and low power output levels. It is shown that the presence of a chaotic attractor is a sufficient condition to predict high power output, though there are relatively small areas where high output is achieved without a chaotic attractor. The chaotic attractor appears as a product of a period doubling cascade or a boundary crisis.

Desynchronization of stochastically synchronized chemical oscillators.

Experimental and theoretical studies are presented on the design of perturbations that enhance desynchronization in populations of oscillators that are synchronized by periodic entrainment. A phase reduction approach is used to determine optimal perturbation timing based upon experimentally measured phase response curves. The effectiveness of the perturbation waveforms is tested experimentally in populations of periodically and stochastically synchronized chemical oscillators.

Clustered Desynchronization from High-Frequency Deep Brain Stimulation.

While high-frequency deep brain stimulation is a well established treatment for Parkinson's disease, its underlying mechanisms remain elusive. Here, we show that two competing hypotheses, desynchronization and entrainment in a population of model neurons, may not be mutually exclusive. We find that in a noisy group of phase oscillators, high frequency perturbations can separate the population into multiple clusters, each with a nearly identical proportion of the overall population.

Determining individual phase response curves from aggregate population data.

Phase reduction is an invaluable technique for investigating the dynamics of nonlinear limit cycle oscillators. Central to the implementation of phase reduction is the ability to calculate phase response curves (PRCs), which describe an oscillator's response to an external perturbation. Current experimental techniques for inferring PRCs require data from individual oscillators, which can be impractical to obtain when the oscillator is part of a much larger population.

Optimal entrainment of heterogeneous noisy neurons.

We develop a methodology to design a stimulus optimized to entrain nonlinear, noisy limit cycle oscillators with uncertain properties. Conditions are derived which guarantee that the stimulus will entrain the oscillators despite these uncertainties. Using these conditions, we develop an energy optimal control strategy to design an efficient entraining stimulus and apply it to numerical models of noisy phase oscillators and to in vitro hippocampal neurons.

An energy-optimal approach for entrainment of uncertain circadian oscillators.

We develop an approach to find an energy-optimal stimulus that entrains an ensemble of uncertain, uncoupled limit cycle oscillators. Furthermore, when entrainment occurs, the phase shift between oscillators is constrained to be less than a predetermined amount. This approach is illustrated for a model of Drosophila circadian activity, for which it performs better than a standard 24-h light-dark cycle.

A Hamilton-Jacobi-Bellman approach for termination of seizure-like bursting.

We use Hamilton-Jacobi-Bellman methods to find minimum-time and energy-optimal control strategies to terminate seizure-like bursting behavior in a conductance-based neural model. Averaging is used to eliminate fast variables from the model, and a target set is defined through bifurcation analysis of the slow variables of the model. This method is illustrated for a single neuron model and for a network model to illustrate its efficacy in terminating bursting once it begins.

Locally optimal extracellular stimulation for chaotic desynchronization of neural populations.

We use optimal control theory to design a methodology to find locally optimal stimuli for desynchronization of a model of neurons with extracellular stimulation. This methodology yields stimuli which lead to positive Lyapunov exponents, and hence desynchronizes a neural population. We analyze this methodology in the presence of interneuron coupling to make predictions about the strength of stimulation required to overcome synchronizing effects of coupling.

Phase noise of oscillators with unsaturated amplifiers.

We study the role of amplifier saturation in eliminating feedback noise in self-sustained oscillators. We extend previous works that use a saturated amplifier to quench fluctuations in the feedback magnitude, while simultaneously tuning the oscillator to an operating point at which the resonator nonlinearity cancels fluctuations in the feedback phase. We consider a generalized model which features an amplitude-dependent amplifier gain function.

Minimum energy control for in vitro neurons.

Objective: To demonstrate the applicability of optimal control theory for designing minimum energy charge-balanced input waveforms for single periodically-firing in vitro neurons from brain slices of Long-Evans rats.

Approach: The method of control uses the phase model of a neuron and does not require prior knowledge of the neuron's biological details. The phase model of a neuron is a one-dimensional model that is characterized by the neuron's phase response curve (PRC), a sensitivity measure of the neuron to a stimulus applied at different points in its firing cycle.

How the spatial position of individuals affects their influence on swarms: a numerical comparison of two popular swarm dynamics models.

Schools of fish and flocks of birds are examples of self-organized animal groups that arise through social interactions among individuals. We numerically study two individual-based models, which recent empirical studies have suggested to explain self-organized group animal behavior: (i) a zone-based model where the group communication topology is determined by finite interacting zones of repulsion, attraction, and orientation among individuals; and (ii) a model where the communication topology is described by Delaunay triangulation, which is defined by each individual's Voronoi neighbors. The models include a tunable parameter that controls an individual's relative weighting of attraction and alignment.

Minimum energy desynchronizing control for coupled neurons.

We employ optimal control theory to design an event-based, minimum energy, desynchronizing control stimulus for a network of pathologically synchronized, heterogeneously coupled neurons. This works by optimally driving the neurons to their phaseless sets, switching the control off, and letting the phases of the neurons randomize under intrinsic background noise. An event-based minimum energy input may be clinically desirable for deep brain stimulation treatment of neurological diseases, like Parkinson's disease.

Homogeneous assumption and the logistic behavior of information propagation.

Many models of disease and rumor-spreading phenomena average the behavior of individuals in a population in order to obtain a coarse description of expected system behavior. For these types of models, we determine how close the coarse approximation is to its corresponding agent-based system. These findings lead to a general result on the logistic behavior of information propagation for networks on both connected graphs with doubly stochastic edge weights, and connected graphs with symmetric edge weights.

Single input optimal control for globally coupled neuron networks.

We consider the problem of desynchronizing a network of synchronized, globally (all-to-all) coupled neurons using an input to a single neuron. This is done by applying the discrete time dynamic programming method to reduced phase models for neural populations. This technique numerically minimizes a certain cost function over the whole state space, and is applied to a Kuramoto model and a reduced phase model for Hodgkin-Huxley neurons with electrotonic coupling.