Kinematic and Neural Dynamics of Postural Instability in Parkinson's Disease

Kinematic and Neural Dynamics of Postural Instability in Parkinson's Disease

Balance problems and falls are among the most common complaints in Veterans with Parkinson's Disease (PD), but there are no effective treatments and the ability to measure balance and falls remains quite poor. This study uses wearable sensors to measure balance and uses deep brain stimulation electrodes to measure electric signals from the brain in Veterans with PD. The investigators hope to use this data to better understand the brain pathways underlying balance problems in PD so that new treatments to improve balance and reduce falls in Veterans with PD can be designed.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that manifests with the cardinal motor signs of bradykinesia, rigidity, tremor and postural instability (PI). Postural instability is a major cause of falls and as the disease process progresses, the most common patient complaints center on gait and balance difficulties leading to falls. Falls are the most common reason for hospitalization in PD patients, impose a significant economic burden to the US healthcare system and are a major cause of diminished quality of life, reduced mobility, disability and death. Both clinical and laboratory-based assessments of balance provide only a brief window of time into patients' function. Prior studies have demonstrated poor correlation between capacity based measurements in the clinic or lab (i.e., what can a patient do when asked) and performance-based measurements in the real world. The investigators have developed methods to use wearable sensors in the ambulatory setting that can accurately detect a variety of activities and have created a number of quantitative metrics that are specific to PI. In this manner, the investigators can monitor and analyze PI in the real world ambulatory setting in Veterans with PD. At present, there are no effective long term treatments for PI. Major impediments to progress in this field are an understanding of how patients actually experience PI at home and categorizing PI into meaningful phenotypic subtypes in order to understand its underlying pathophysiology and evaluate new treatments.

The goal of this project is to better understand the underlying kinematic and electrophysiological components of postural instability in Veterans with PD. Aim 1 sends PD patients home for one week with five wearable sensors and a neck-worn video camera to create a massive video-validated quantitative dataset of a variety of events that are relevant to analyzing PI at home (walking, turning, sit to stand transitions, near falls/stumbles). For each video-validated event, the investigators use deep learning algorithms to predict which activity occurred and create ROC curves to examine the algorithms' predictive accuracy. Aim 2 will use kinematic data obtained from the wearable sensors to develop "deep clinical phenotypes" of postural instability using principal component analysis (PCA) and unsupervised clustering machine learning methods. Using these deep clinical phenotypes, the investigators will then test specific hypotheses related to patients' future fall risk, their experience of PI at home and the relationship of these phenotypes to clinical data such as the presence of co-morbidities like peripheral neuropathy. In Aim 3, a subset of Veterans with PD from the first two aims will undergo subthalamic nucleus (STN) DBS. The investigators will use local field potential recordings from their leads to understand the physiological signature(s) that occur just prior to, during and after a perturbation evoking a reactive postural response. By recording from contacts in motor and associative regions while undergoing simultaneous kinematic recordings and associative STN stimulation, the investigators can investigate the physiological basis of postural instability in these patients.

Inclusion Criteria:

Aims 1 and 2 Inclusion criteria:

• All Veterans with a clinical diagnosis of Parkinson's disease as made by their treating neurologist in Hoehn and Yahr stage 2-3 with the ability to give informed consent will be considered for possible participation in this study.

• Veterans cannot be past stage 3 as our measures depend on physical independence and fall risk prediction is less useful after stage 3.

• Capacity to consent will be assessed with the University of California, San Diego Brief Assessment of Capacity to Consent (UBACC).

  • A score of less than 14.5 will be used as the cut-off to decide whether a Veteran is capable of consenting as the false positive rate is zero below this score with marginal increases in sensitivity above this score (89% sensitivity, 100% specificity).

Aim 3

Inclusion criteria:

• In addition to the inclusion criteria for Aims 1 and 2, Veterans with an implanted STN DBS lead with a Percept device in place.

Exclusion Criteria:

Aims 1 and 2 Exclusion criteria:

• Veterans with dementia of sufficient severity to impair their ability to make healthcare related decisions for themselves will be excluded.
• Veterans with other forms of parkinsonism (PSP, CBGD, etc.) will be excluded.
• Veterans past H&Y Stage 3 will be excluded.
• Veterans with symptomatic orthostatic hypotension (defined as sustained drop in systolic blood pressure by 20 mmHg or diastolic blood pressure by 10 mmHg within 3 minutes of standing after being supine for five minutes) will also be excluded as this is an entity the investigators are not characterizing and could confound/bias the dataset.

Aim 3:

Exclusion criteria:

• In addition to the exclusion criteria for Aims 1 and 2, Veterans with DBS leads implanted in other locations will be excluded.