Control and Synchronization of Neuron Ensembles

Synchronization of oscillations is a phenomenon prevalent in natural, social, and engineering systems. Controlling synchronization of oscillating systems is motivated by a wide range of applications from neurological treatment of Parkinson's disease to the design of neurocomputers. In this article, we study the control of an ensemble of uncoupled neuron oscillators described by phase models. We examine controllability of such a neuron ensemble for various phase models and, furthermore, study the related optimal control problems. In particular, by employing Pontryagin's maximum principle, we analytically derive optimal controls for spiking single- and two-neuron systems, and analyze the applicability of the latter to an ensemble system. Finally, we present a robust computational method for optimal control of spiking neurons based on pseudospectral approximations. The methodology developed here is universal to the control of general nonlinear phase oscillators.Comment: 29 pages, 6 figure

Actomyosin Contractility in Nonmuscle Cells

Forces and stresses generated by the action of myosin minifilaments are analyzed via simulation of their motion in idealized computer-generated random, isotropic actin networks and actin bundles. The networks and bundles are generated as random collections of actin filaments in two dimensions with constrained orientations, crosslinked and attached to fixed walls: four walls for isotropic networks, two for bundles). Myosin minifilaments are placed on actin filament pairs and allowed to move and deform the network so that it exerts forces on the walls. The stresses are overwhelmingly contractile in both cases, because minifilament equilibrium positions having contractile stress have lower energy than those for expansive stress. Mini-filaments rotate into these energetically stable contractile configurations. This process is aided by the bending of actin filaments, which accomodates mini-filament rotation. The presence of force chains leads to unexpectedly large stresses especially in the random networks. Stresses for bundles are greater than those for isotropic networks, and antiparallel filaments generate more tension than parallel filaments. The forces transmitted by the actin network to the walls of the simulation cell often exceed the tension in the minifilament itself

Optimal Control of Weakly Forced Nonlinear Oscillators

Optimal control of nonlinear oscillatory systems poses numerous theoretical and computational challenges. Motivated by applications in neuroscience, we develop tools and methods to synthesize optimal controls for nonlinear oscillators described by reduced order dynamical systems. Control of neural oscillations by external stimuli has a broad range of applications, ranging from oscillatory neurocomputers to deep brain stimulation for Parkinson\u27s disease. In this dissertation, we investigate fundamental limits on how neuron spiking behavior can be altered by the use of an external stimulus: control). Pontryagin\u27s maximum principle is employed to derive optimal controls that lead to desired spiking times of a neuron oscillator, which include minimum-power and time-optimal controls. In particular, we consider practical constraints in such optimal control designs including a bound on the control amplitude and the charge-balance constraint. The latter is important in neural stimulations used to avoid from the undesirable effects caused by accumulation of electric charge due to external stimuli. Furthermore, we extend the results in controlling a single neuron and consider a neuron ensemble. We, specifically, derive and synthesize time-optimal controls that elicit simultaneous spikes for two neuron oscillators. Robust computational methods based on homotopy perturbation techniques and pseudospectral approximations are developed and implemented to construct optimal controls for spiking and synchronizing a neuron ensemble, for which analytical solutions are intractable. We finally validate the optimal control strategies derived using the models of phase reduction by applying them to the corresponding original full state-space models. This validation is largely missing in the literature. Moreover, the derived optimal controls have been experimentally applied to control the synchronization of electrochemical oscillators. The methodology developed in this dissertation work is not limited to the control of neural oscillators and can be applied to a broad class of nonlinear oscillatory systems that have smooth dynamics

Charge-Balanced Minimum-Power Controls for Spiking Neuron Oscillators

In this paper, we study the optimal control of phase models for spiking neuron oscillators. We focus on the design of minimum-power current stimuli that elicit spikes in neurons at desired times. We furthermore take the charge-balanced constraint into account because in practice undesirable side effects may occur due to the accumulation of electric charge resulting from external stimuli. Charge-balanced minimum-power controls are derived for a general phase model using the maximum principle, where the cases with unbounded and bounded control amplitude are examined. The latter is of practical importance since phase models are more accurate for weak forcing. The developed optimal control strategies are then applied to both mathematically ideal and experimentally observed phase models to demonstrate their applicability, including the phase model for the widely studied Hodgkin-Huxley equations.Comment: 24 pages, 12 figure

Adverse Perinatal Outcomes in COVID-19 Infected Pregnant Women: A Systematic Review and Meta-Analysis.

The impact of COVID-19 virus infection during pregnancy is still unclear. This systematic review and meta-analysis aimed to quantitatively pool the evidence on impact of COVID-19 infection on perinatal outcomes. Databases of Medline, Embase, and Cochrane library were searched using the keywords related to COVID-19 and perinatal outcomes from December 2019 to 30 June 2021. Observational studies comparing the perinatal outcomes of COVID-19 infection in pregnancy with a non-infected comparator were included. The screening process and quality assessment of the included studies were performed independently by two reviewers. Meta-analyses were used to pool the comparative dichotomous data on perinatal outcomes. The database search yielded 4049 results, 1254 of which were duplicates. We included a total of 21 observational studies that assessed the adverse perinatal outcomes with COVID-19 infection. The odds of maternal death (pooled OR: 7.05 [2.41-20.65]), preeclampsia (pooled OR: 1.39 [1.29-1.50]), cesarean delivery (pooled OR: 1.67 [1.29-2.15]), fetal distress (pooled OR: 1.66 [1.35-2.05]), preterm birth (pooled OR: 1.86 [1.34-2.58]), low birth weight (pooled OR: 1.69 [1.35-2.11]), stillbirth (pooled OR: 1.46 [1.16-1.85]), 5th minute Apgar score of less than 7 (pooled OR: 1.44 [1.11-1.86]) and admissions to neonatal intensive care unit (pooled OR: 2.12 [1.36-3.32]) were higher among COVID-19 infected pregnant women compared to non-infected pregnant women

Tooth Decay in Alcohol Abusers Compared to Alcohol and Drug Abusers

Alcohol and drug abuse are detrimental to general and oral health. Though we know the effects of these harmful habits on oral mucosa, their independent and combined effect on the dental caries experience is unknown and worthy of investigation. We compared 363 “alcohol only” abusers to 300 “alcohol and drug” abusers to test the hypothesis that various components of their dental caries experience are significantly different due to plausible sociobiological explanations. After controlling for the potential confounders, we observe that the “alcohol and drug” group had a 38% higher risk of having decayed teeth compared to the “alcohol only” group (P < .05). As expected, those who belonged to a higher social class (OR = 1.98; 95%  CI = 1.43–2.75) and drank wine (OR = 1.85; 95%  CI = 1.16–2.96) had a higher risk of having more filled teeth. We conclude that the risk of tooth decay among “alcohol only” abusers is significantly lower compared to “alcohol and drug” abusers