Dataset Information

Disentangling stability and flexibility degrees in Parkinson's disease using a computational postural control model.

ABSTRACT:

Background

Impaired postural control in Parkinson's disease (PD) seriously compromises life quality. Although balance training improves mobility and postural stability, lack of quantitative studies on the neurophysiological mechanisms of balance training in PD impedes the development of patient-specific therapies. We evaluated the effects of a balance-training program using functional balance and mobility tests, posturography, and a postural control model.

Methods

Center-of-pressure (COP) data of 40 PD patients before and after a 12-session balance-training program, and 20 healthy control subjects were recorded in four conditions with two tasks on a rigid surface (R-tasks) and two on foam. A postural control model was fitted to describe the posturography data. The model comprises a neuromuscular controller, a time delay, and a gain scaling the internal disturbance torque.

Results

Patients' axial rigidity before training resulted in slower COP velocity in R-tasks; which was reflected as lower internal torque gain. Furthermore, patients exhibited poor stability on foam, remarked by abnormal higher sway amplitude. Lower control parameters as well as higher time delay were responsible for patients' abnormal high sway amplitude. Balance training improved all clinical scores on functional balance and mobility. Consistently, improved 'flexibility' appeared as enhanced sway velocity (increased internal torque gain). Balance training also helped patients to develop the 'stability degree' (increase control parameters), and to respond more quickly in unstable condition of stance on foam.

Conclusions

Projection of the common posturography measures on a postural control model provided a quantitative framework for unraveling the neurophysiological factors and different recovery mechanisms in impaired postural control in PD.

SUBMITTER: Rahmati Z

PROVIDER: S-EPMC6694532 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

Disentangling stability and flexibility degrees in Parkinson's disease using a computational postural control model.

Rahmati Zahra Z Schouten Alfred C AC Behzadipour Saeed S Taghizadeh Ghorban G Firoozbakhsh Keikhosrow K

Journal of neuroengineering and rehabilitation 20190814 1

<h4>Background</h4>Impaired postural control in Parkinson's disease (PD) seriously compromises life quality. Although balance training improves mobility and postural stability, lack of quantitative studies on the neurophysiological mechanisms of balance training in PD impedes the development of patient-specific therapies. We evaluated the effects of a balance-training program using functional balance and mobility tests, posturography, and a postural control model.<h4>Methods</h4>Center-of-pressu ...[more]

PMID: 31412926

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Project description:Numerous quantitative stability/flexibility relationships, within Escherichia coli thioredoxin (Trx) and its fragments are determined using a minimal distance constraint model (DCM). A one-dimensional free energy landscape as a function of global flexibility reveals Trx to fold in a low-barrier two-state process, with a voluminous transition state. Near the folding transition temperature, the native free energy basin is markedly skewed to allow partial unfolded forms. Under native conditions the skewed shape is lost, and the protein forms a compact structure with some flexibility. Predictions on ten Trx fragments are generally consistent with experimental observations that they are disordered, and that complementary fragments reconstitute. A hierarchical unfolding pathway is uncovered using an exhaustive computational procedure of breaking interfacial cross-linking hydrogen bonds that span over a series of fragment dissociations. The unfolding pathway leads to a stable core structure (residues 22-90), predicted to act as a kinetic trap. Direct connection between degree of rigidity within molecular structure and non-additivity of free energy is demonstrated using a thermodynamic cycle involving fragments and their hierarchical unfolding pathway. Additionally, the model provides insight about molecular cooperativity within Trx in its native state, and about intermediate states populating the folding/unfolding pathways. Native state cooperativity correlation plots highlight several flexibly correlated regions, giving insight into the catalytic mechanism that facilitates access to the active site disulfide bond. Residual native cooperativity correlations are present in the core substructure, suggesting that Trx can function when it is partly unfolded. This natively disordered kinetic trap, interpreted as a molten globule, has a wide temperature range of metastability, and it is identified as the "slow intermediate state" observed in kinetic experiments. These computational results are found to be in overall agreement with a large array of experimental data.

Dataset Information

Disentangling stability and flexibility degrees in Parkinson's disease using a computational postural control model.

Background

Methods

Results

Conclusions

Publications

Disentangling stability and flexibility degrees in Parkinson's disease using a computational postural control model.

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