The purpose of this project is to increase our understanding of the early state and temporal evolution of neuroplastic changes in the cortex and subthalamic nucleus (STN) of people with PD, and the relationship of these changes to the emergence and expression of PD motor and non-motor signs. Neurophysiological biomarkers derived from this work may be important for the early detection and prediction of progression of disease. They can also provide the means to assess the efficacy of interventions designed to prevent or slow disease progression.

This project will use neuroimaging (7T MRI: structural, diffusion and rest-state functional MRI), from Dr. Noam Harel's protocol IRB# STUDY00008096, and non-invasive brain stimulation (TMS: PAS. SAI) techniques to quantify structural and functional changes in brain function. The TMS experiment will use a Magstim Bistimn 2002 transcranial magnetic stimulation (TMS) unit and standard figure-of-eight coil (70 mm diameter) to deliver stimulation on the surface of the scalp. Stimulation will be delivered using either a single pulse or with a paired-pulse protocol (two stimuli, through the same TMS coil at inter-stimulus intervals of 50 or 80 ms). All surface EMG signals will be pre-amplified within the sensor and sent wirelessly via blue-tooth connection to a Delsys data collection system. Quantitative assessments of motor function (gait, gait initiation, reactive balance, bradykinesia, repetitive alternating movements, rigidity, stop-signal reaction time), and neuropsychological function will used to assess behavioral status at baseline and 30-36 months later.

Inclusion Criteria:

Participants with PD

• Diagnosis of idiopathic PD, as determined by a movement disorders neurologist in accordance with the PD Society Brain Bank diagnostic criteria
• Not receiving levodopa or dopamine agonist to treat PD (at baseline)
• Able to ambulate independently without the use of an assistive device (e.g. cane) for 50 meters Healthy Controls
• Age- (+/- 3 years) and sex-matched to participants with PD
• Able to ambulate independently without the use of an assistive device (e.g. cane) for 50 meters

Exclusion Criteria:

• Dementia diagnosis and/or a University of California Brief Assessment of Capacity to Consent (UBACC) score and MacCAT-CR score indicating impaired capacity to consent
• History of musculoskeletal disorders that significant affect movement of lower or upper limbs as determined at the time of enrollment
• History of bipolar disorder, post-traumatic stress disorder or major depressive disorder
• Other significant neurological disorders that may affect participation or performance in the study
• Implanted DBS or other neurosurgeries to treat PD
• Pregnancy

Additional exclusion criteria for TMS experiments (note that individuals who are excluded from the TMS experiment still have the opportunity to participate in the other data collection sessions):

• History of seizures, epilepsy, stroke, multiple sclerosis, or traumatic brain injury
• Recent history of frequent syncope (fainting) episodes in response to blood, emotional stress, or sensory triggers.
• Intracranial metallic or magnetic devices (e.g. cochlear implant, deep brain stimulator)
• Pacemaker or any implanted device
• History of surgery on blood vessels, brain, or heart
• Unexplained, recurring headaches or concussion within the last six months
• Severe hearing impairment

Adults diagnosed with Parkinson's Disease (early diagnosis, currently untreated) and age- and sex-matched healthy controls