arXiv subjects

Timothy J. Lewis

Publications and source records attributed to Timothy J. Lewis.

5 recordsLinked to original sources

arXiv2026

Adaptive Hybrid Subspace Levenberg Marquardt Algorithm with Adequacy Monitor for Large Scale Least Squares Problems

The Levenberg-Marquardt (LM) algorithm is the most widely used method for solving nonlinear least-squares problems, as it combines the robustness of steepest descent with the fast local convergence of the Gauss-Newton method. However, its computational cost can become prohibitive for large-scale problems because each iteration requires solving a large damped linear system, and conventional step acceptance strategies may require repeated solves as the damping parameter is adjusted. Despite this computational challenge, many large-scale least-squares problems exhibit effective low-dimensional structure, with only a small number of parameter-space directions strongly informed by the data. We propose an adaptive hybrid subspace Levenberg-Marquardt (HSLM) algorithm that constructs a low-dimensional subspace from complementary sources of gradient, memory, Krylov-subspace, and randomized curvature information and computes a spectrally damped LM step within this subspace. A distinguishing feature of the method is a deterministic adequacy monitor that quantifies how much descent information is captured by the reduced space and adaptively enriches the subspace when necessary. Step acceptance is decoupled from damping adjustment: Armijo backtracking determines the accepted step length, while the ratio of actual to predicted reduction is used solely to update the damping parameter, thereby avoiding repeated damped-system solves during step acceptance. For the HSLM algorithm, we establish global convergence to stationarity and prove local linear and superlinear convergence. Numerical experiments on neural-network training problems show that HSLM achieves convergence behavior comparable to classical and Krylov subspace LM (KSLM) while substantially reducing per-iteration computational cost, with increasing advantages observed as the parameter dimension grows.

math.NA↗

arXiv2021

Reflections in excitable media linked to existence and stability of one-dimensional spiral waves

When propagated action potentials in cardiac tissue interact with local heterogeneities, reflected waves can sometimes be induced. These reflected waves have been associated with the onset of cardiac arrhythmias, and while their generation is not well understood, their existence is linked to that of one-dimensional (1D) spiral waves. Thus, understanding the existence and stability of 1D spirals plays a crucial role in determining the likelihood of the unwanted reflected pulses. Mathematically, we probe these issues by viewing the 1D spiral as a time-periodic antisymmetric source defect. Through a combination of direct numerical simulation and continuation methods, we investigate existence and stability of a 1D spiral wave in a qualitative ionic model to determine how the systems propensity for reflections are influenced by system parameters. Our results support and extend a previous hypothesis that the 1D spiral is an unstable periodic orbit that emerges through a global rearrangement of heteroclinic orbits and we identify key parameters and physiological processes that promote and deter reflection behavior.

math.DS↗

arXiv2021

Neuromechanical Mechanisms of Gait Adaptation in C. elegans: Relative Roles of Neural and Mechanical Coupling

Understanding principles of neurolocomotion requires the synthesis of neural activity, sensory feedback, and biomechanics. The nematode \textit{C. elegans} is an ideal model organism for studying locomotion in an integrated neuromechanical setting because its neural circuit has a well-characterized modular structure and its undulatory forward swimming gait adapts to the surrounding fluid with a shorter wavelength in higher viscosity environments. This adaptive behavior emerges from the neural modules interacting through a combination of mechanical forces, neuronal coupling, and sensory feedback mechanisms. However, the relative contributions of these coupling modes to gait adaptation are not understood. The model consists of repeated neuromechanical modules that are coupled through the mechanics of the body, short-range proprioception, and gap-junctions. The model captures the experimentally observed gait adaptation over a wide range of mechanical parameters, provided that the muscle response to input from the nervous system is faster than the body response to changes in internal and external forces. The modularity of the model allows the use of the theory of weakly coupled oscillators to identify the relative roles of body mechanics, gap-junctional coupling, and proprioceptive coupling in coordinating the undulatory gait. The analysis shows that the wavelength of body undulations is set by the relative strengths of these three coupling forms. In a low-viscosity fluid environment, the competition between gap-junctions and proprioception produces a long wavelength undulation, which is only achieved in the model with sufficiently strong gap-junctional coupling.The experimentally observed decrease in wavelength in response to increasing fluid viscosity is the result of an increase in the relative strength of mechanical coupling, which promotes a short wavelength.

q-bio.NC↗

arXiv2021

Rate-dependent effects of lidocaine on cardiac dynamics: Development and analysis of a low-dimensional drug-channel interaction model

State-dependent Na+ channel blockers are often prescribed to treat cardiac arrhythmias, but many Na+ channel blockers are known to have pro-arrhythmic side effects. While the anti and proarrhythmic potential of a Na+ channel blocker is thought to depend on the characteristics of its rate-dependent block, the mechanisms linking these two attributes are unclear. Furthermore, how specific properties of rate-dependent block arise from the binding kinetics of a particular drug is poorly understood. Here, we examine the rate-dependent effects of the Na+ channel blocker lidocaine by constructing and analyzing a novel drug-channel interaction model. First, we identify the predominant mode of lidocaine binding in a 24 variable Markov model for lidocaine-Na+ channel interaction by Moreno et al. We then develop a novel 3-variable lidocaine-Na+ channel interaction model that incorporates only the predominant mode of drug binding. Our low-dimensional model replicates the extensive voltage-clamp data used to parameterize the Moreno et al. model. Furthermore, the effects of lidocaine on action potential upstroke velocity and conduction velocity in our model are similar to those predicted by the Moreno et al. model. By exploiting the low-dimensionality of our model, we derive an algebraic expression for level of rate-dependent block as a function of pacing frequency, restitution properties, diastolic and plateau potentials, and drug binding rate constants. Our model predicts that the level of rate-dependent block is sensitive to alterations in restitution properties and increases in diastolic potential, but it is insensitive to variations in the shape of the action potential waveform and lidocaine binding rates.

q-bio.QM↗

arXiv2018

Synchronization of electrically coupled resonate-and-fire neurons

Electrical coupling between neurons is broadly present across brain areas and is typically assumed to synchronize network activity. However, intrinsic properties of the coupled cells can complicate this simple picture. Many cell types with strong electrical coupling have been shown to exhibit resonant properties, and the subthreshold fluctuations arising from resonance are transmitted through electrical synapses in addition to action potentials. Using the theory of weakly coupled oscillators, we explore the effect of both subthreshold and spike-mediated coupling on synchrony in small networks of electrically coupled resonate-and-fire neurons, a hybrid neuron model with linear subthreshold dynamics and discrete post-spike reset. We calculate the phase response curve using an extension of the adjoint method that accounts for the discontinuity in the dynamics. We find that both spikes and resonant subthreshold fluctuations can jointly promote synchronization. The subthreshold contribution is strongest when the voltage exhibits a significant post-spike elevation in voltage, or plateau. Additionally, we show that the geometry of trajectories approaching the spiking threshold causes a "reset-induced shear" effect that can oppose synchrony in the presence of network asymmetry, despite having no effect on the phase-locking of symmetrically coupled pairs.

nlin.AO↗