Effects of Vagal Nerve Stimulation on Leg Muscle Activity and Posture in Parkinson's Disease

The Effects of Vagus Nerve Stimulation on Intrinsic Lower Leg Spinal Motoneuron Excitability in Parkinson's Disease.

This study is designed to better understand the mechanisms contributing to impaired activation of leg muscles in people with Parkinson's disease (PD) and to test if stimulation of a nerve at the neck can improve muscle activation, walking and balance.

The goals of this project are twofold: (i) to test the hypothesis that persistent inward currents (PICs) in spinal motoneurons of the ankle extensors are reduced in people with Parkinson's disease and that these changes are associated with impaired postural control and (ii) to examine the acute effects of non-invasive vagus nerve stimulation (nVNS) on PICs and postural control.

This project will conduct experiments to test the hypothesis that the firing properties of muscles that control the ankle are significantly altered in people with PD compared to matched healthy adults and that these changes in activity are related to the severity of postural control deficits. In addition, this project will examine the acute effects of non-invasive vagal nerve stimulation (nVNS), an intervention that increases activity in the locus coeruleus and raphe nucleus, on the firing properties of ankle muscles and postural control. If successful, this work will be the first to demonstrate that brainstem pathways that control muscle firing properties are altered in people with PD and are associated with postural impairment. The preliminary trial of nVNS will provide evidence that postural muscle activity can be improved with stimulation and improve postural control. These findings will provide critical preliminary data required to move forward with a clinical trial of nVNS in PD.

Inclusion Criteria:

• Diagnosis of idiopathic Parkinson's disease,
• On stable medication for the preceding month and anticipated over the next 3 months,
• Able to ambulate without the use of an assistive device for more than 50 meters.

Control Cohort:

• Age (± 3 years) and sex distribution matched to the PD cohort,
• Able to ambulate without the use of an assistive device for more than 50 meters.

Exclusion Criteria:

• Failure to demonstrate capacity to consent (based on UBACC and/or MacArthur-CR),
• History of significant neurological disorder (besides PD in the PD group),
• History of stroke, traumatic brain injury, intracranial aneurysm, intracranial hemorrhage, brain tumor or atypical parkinsonian disorder,
• Severe orthopedic or other related musculoskeletal pathology that has significant adverse effects on gait,
• Women who are pregnant or may be pregnant,
• Insufficient comprehension of the English language,
• History of substance abuse in past 2 years;

Additional exclusion criteria for VNS experiment

• Pain at the nVNS treatment site (e.g., dysesthesia, neuralgia, cervicalgia);
• Lesion (including lymphadenopathy), previous surgery (including carotid endarterectomy or vascular neck surgery) or abnormal anatomy at the stimulation site (open wound, rash, infection, swelling, cut, sore, drug patch, surgical scar[s]);
• Known or suspected severe atherosclerotic cardiovascular disease, severe carotid artery disease (e.g., bruits or history of TIA or stroke), congestive heart failure, known severe coronary artery disease or prior myocardial infarction;
• Abnormal baseline electrocardiogram (ECG) within the last year (e.g., second or third-degree heart block, prolonged QT interval, atrial fibrillation, atrial flutter, history of ventricular tachycardia or ventricular fibrillation);
• Recent history of uncontrolled high blood pressure, bradycardia, tachycardia, or know recent history orthostatic hypotension;
• Previous unilateral or bilateral vagotomy;
• Implanted metal cervical spine hardware, other metallic implants or implantable medical devices such as deep brain stimulator, hearing aid implant, pacemaker, implanted cardioverter defibrillator, cranial aneurysm and/or cranial aneurysm clips, history of facial/orbital/metallic fragments, implanted electronic device, neurostimulator, valve replacements/stents, metallic implants/prostheses) near the stimulation site such as a bone plate or bone screw;
• History of syncope or seizures (within the last 2 years);