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. In the present study, we investigate how the number of clusters and their stability properties, bifurcations, and basins of attraction can be understood in terms of one-dimensional maps defined on the circle. Moreover, we generalize this analysis to stimuli that consist of pulses with alternating properties, which provide additional degrees of freedom in the design of DBS stimuli. Our results illustrate how the complicated properties of clustering behavior for periodically forced neural oscillator populations can be understood in terms of a much simpler dynamical system.

Low dose radiation therapy as a potential life saving treatment for COVID-19-induced acute respiratory distress syndrome (ARDS).

The new coronavirus COVID-19 disease caused by SARS-CoV-2 was declared a global public health emergency by WHO on Jan 30, 2020. Despite massive efforts from various governmental, health and medical organizations, the disease continues to spread globally with increasing fatality rates. Several experimental drugs have been approved by FDA with unknown efficacy and potential adverse effects. The exponentially spreading pandemic of COVID-19 deserves prime public health attention to evaluate yet unexplored arenas of management. We opine that one of these treatment options is low dose radiation therapy for severe and most critical cases. There is evidence in literature that low dose radiation induces an anti-inflammatory phenotype that can potentially afford therapeutic benefit against COVID-19-related complications that are associated with significant morbidity and mortality. Herein, we review the effects and putative mechanisms of low dose radiation that may be viable, useful and of value in counter-acting the acute inflammatory state induced by critical stage COVID-19.

Necrotizing Fasciitis: Low-Dose Radiotherapy as a Potential Adjunct Treatment.

Necrotizing fasciitis (NF) is a rapidly spreading bacterial infection causing extensive tissue necrosis and destruction. Despite appropriate therapy, the disease results in significant morbidity/mortality and substantial treatment costs. Several studies published in the early 1900s demonstrated the effective use of low-dose X-ray radiotherapy (RT) for the treatment of many diverse inflammatory conditions and diseases (eg, gas gangrene, sinus infections, arthritis, tendonitis, and serious inflammatory lung conditions). The mechanism by which therapeutic RT doses produce positive patient outcomes is related at least in part to its capacity to induce tissue-based anti-inflammatory responses. This action is due to the polarization of macrophages to an anti-inflammatory or M2 phenotype via optimized low-dose RT. Low-dose RT has the potential to significantly reduce debilitating surgeries and aggressive treatments required for NF, providing a 3-prong benefit in terms of patient mortality, length of hospitalization stays, and cost of health care (both short term and long term). Low cost and easy availability of low-dose RT makes it a potentially useful option for patients of every age-group. In addition, low-dose RT may be a particularly useful option in countries treating many patients who are unable to afford surgeries, antibiotics, and hyperbaric oxygen.

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. It also covers the use of phase reduction for designing control algorithms which optimally change properties of the system, such as the phase of the oscillation. The control techniques are illustrated for example neural and cardiac systems.

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. We also describe how the devised algorithm can be used for spike timing control which can potentially help with motor symptoms of essential and parkinsonian tremor, and aid in treating jet lag. To demonstrate the advantages of this algorithm, we compare it with a previously proposed optimal control algorithm based on standard phase reduction for the Hopf bifurcation normal form, and models for cardiac pacemaker cells, thalamic neurons, and circadian gene regulation cycle in the suprachiasmatic nucleus. We show that our control algorithm is effective even when a large phase change is required or when the nontrivial Floquet multiplier is close to unity; in such cases, the previously proposed control algorithm fails.