This is a mechanistic study to determine the differential effects of the dopaminergic and cholinergic systems on attention, gait, and balance. The primary goal of the study is to evaluate the relative effects of pedunculopontine nucleus (PPN) and subthalamic nucleus (STN) Deep Brain Stimulation (DBS) on these features in persons with Parkinson's Disease (PD) who are eligible for DBS for improvement of their motor symptoms and exhibit gait instability with falls. Patients will be enrolled and implanted with bilateral electrodes in one of the approved DBS locations (subthalamic nucleus: STN), but additionally electrodes will be inserted into the experimental target, namely the PPN bilaterally.

This is a prospective, single-center randomized controlled trial designed to estimate the potential clinical benefit, and associated risks, of deep brain stimulation of the of the PPN and STN in patients with PD that are candidates for DBS for improvement of their motor symptoms and exhibit gait instability with falls. Patients will be enrolled and implanted with additional bilateral electrodes in the PPN. Each subject will be randomized 1:1 to one of the following sequences: Bilateral STN+PPN stimulation or Bilateral STN stimulation alone. The addition of a bilateral STN stimulation only group allows for the research of potential micro-lesioning effects of the PPN which might affect features of interest even in the absence of PPN stimulation.

Inclusion Criteria:

• Inclusion Criteria

  1. Informed consent signed by the subject.
  2. Diagnosed with Parkinson's disease per UK Parkinson's Disease Society Brain Bank (Queens Square) criteria for at least 4 years
  3. Demonstrates levodopa responsiveness of at least 30%
  4. Experiences tremor or motor complications including wearing off and/or dyskinesia
  5. DBS candidate per FDA guidelines as outlined in criteria 2-4
  6. Candidate for STN targeting per the consensus committee
  7. Subject exhibits gait instability, or a history of at least one fall within the last year, or a history of falls on tests of Static or Dynamic Stability.
  8. PD Stage 2-3 with predominant axial symptoms or FOG refractory to Levodopa > 600 mg and UPDRS Part III Subscore of >6.
  9. Subject is ambulatory and able to walk for limited periods of time without using an assistive device.
  10. 18-75 years of age
  11. Primary English speaking
  12. Physically and cognitively capable of completing evaluations and consent
  13. Medically cleared for surgery and anesthesia
  14. Female subjects with child-bearing potential have a negative serum pregnancy test prior to DBS surgery

Exclusion Criteria:

Exclusion Criteria:

1. Dementia per DSM-V criteria
2. Condition precluding MRI
3. History of supraspinal CNS disease other than PD
4. History of schizophrenia, delusions, or currently uncontrolled visual hallucinations
5. Subjects who require rTMS, ECT, diathermy, or repeat MRI procedures to treat a medical condition.
6. Subjects with a history of seizure disorder
7. Subjects who have made a suicide attempt within the prior year,
8. Subjects with any medical contraindications to undergoing DBS surgery (eg, infection, coagulopathy, or significant cardiac or other medical risk factors for surgery)
9. Subjects with an implanted stimulator such as a cardiac pacemaker, defibrillator, neurostimulator and cochlear implant
10. Subjects who are pregnant or nursing.
11. Patient that is unwilling or unable to comply with the requirements of this protocol, including the presence of any condition (physical, mental, or social) that is likely to affect the subject's ability to comply with the protocol.
12. Any other reasons that, in the opinion of the investigator, the candidate is determined to be unsuitable for entry into the study.

There is a Data Use Agreement (DUA), with Boston Scientific.