Deep brain stimulation effectively alleviates motor symptoms of medically refractory Parkinson's disease, and also relieves many other treatment-resistant movement and affective disorders. Despite its relative success as a treatment option, the basis of its efficacy remains elusive. In Parkinson's disease, increased functional connectivity and oscillatory activity occur within the basal ganglia as a result of dopamine loss. A correlative relationship between pathological oscillatory activity and the motor symptoms of the disease, in particular bradykinesia, rigidity, and tremor, has been established. Suppression of the oscillations by either dopamine replacement or DBS also correlates with an improvement in motor symptoms. DBS parameters are currently chosen empirically using a "trial and error" approach, which can be time-consuming and costly. The work presented here amalgamates concepts from theories of neural network modeling with nonlinear control engineering to describe and analyze a model of synchronous neural activity and applied stimulation. A theoretical expression for the optimum stimulation parameters necessary to suppress oscillations is derived. The effect of changing stimulation parameters (amplitude and pulse duration) on induced oscillations is studied in the model. Increasing either stimulation pulse duration or amplitude enhanced the level of suppression. The predicted parameters were found to agree well with clinical measurements reported in the literature for individual patients. It is anticipated that the simplified model described may facilitate the development of protocols to aid optimum stimulation parameter choice on a patient by patient basis.

Parkinson's disease is a progressive, neurodegenerative disorder, characterized by hallmark motor symptoms. It is associated with pathological, oscillatory neural activity in the basal ganglia. Deep brain stimulation (DBS) is often successfully used to treat medically refractive Parkinson's disease. However, the selection of stimulation parameters is based on qualitative assessment of the patient, which can result in a lengthy tuning period and a suboptimal choice of parameters. This study explores fourth-order, control theory-based models of oscillatory activity in the basal ganglia. Describing function analysis is applied to examine possible mechanisms for the generation of oscillations in interacting nuclei and to investigate the suppression of oscillations with high-frequency stimulation. The theoretical results for the suppression of the oscillatory activity obtained using both the fourth-order model, and a previously described second-order model, are optimized to fit clinically recorded local field potential data obtained from Parkinsonian patients with implanted DBS. Close agreement between the power of oscillations recorded for a range of stimulation amplitudes is observed ( R(2)=0.69-0.99 ). The results suggest that the behavior of the system and the suppression of pathological neural oscillations with DBS is well described by the macroscopic models presented. The results also demonstrate that in this instance, a second-order model is sufficient to model the clinical data, without the need for added complexity. Describing the system behavior with computationally efficient models could aid in the identification of optimal stimulation parameters for patients in a clinical environment.

BackgroundAcute respiratory syndrome due to coronavirus 2 (SARS-CoV-2) is characterised by heterogeneous levels of disease severity. It is not necessarily apparent whether a patient will develop a severe disease or not. This cross-sectional study explores whether acoustic properties of the cough sound of patients with coronavirus disease (COVID-19), the illness caused by SARS-CoV-2, correlate with their disease and pneumonia severity, with the aim of identifying patients with a severe disease.MethodsVoluntary cough sounds were recorded using a smartphone in 70 COVID-19 patients within the first 24 h of their hospital arrival, between April 2020 and May 2021. Based on gas exchange abnormalities, patients were classified as mild, moderate, or severe. Time- and frequency-based variables were obtained from each cough effort and analysed using a linear mixed-effects modelling approach.ResultsRecords from 62 patients (37% female) were eligible for inclusion in the analysis, with mild, moderate, and severe groups consisting of 31, 14 and 17 patients respectively. 5 of the parameters examined were found to be significantly different in the cough of patients at different disease levels of severity, with a further 2 parameters found to be affected differently by the disease severity in men and women.ConclusionsWe suggest that all these differences reflect the progressive pathophysiological alterations occurring in the respiratory system of COVID-19 patients, and potentially would provide an easy and cost-effective way to initially stratify patients, identifying those with more severe disease, and thereby most effectively allocate healthcare resources.

Deep brain stimulation (DBS) effectively alleviates the pathological neural activity associated with Parkinson's disease. Its exact mode of action is not entirely understood. This paper explores theoretically the optimum stimulation parameters necessary to quench oscillations in a neural-mass type model with second order dynamics. This model applies well established nonlinear control system theory to DBS. The analysis here determines the minimum criteria in terms of amplitude and pulse duration of stimulation, necessary to quench the unwanted oscillations in a closed loop system, and outlines the relationship between this model and the actual physiological system.