Biomarkers to Guide Directional DBS for Parkinson's Disease

Inclusion Criteria

• Age ≥18 years and ≤70 years.
• Clinically definite, advanced idiopathic PD based on at least 2 of 3 cardinal PD features (tremor, rigidity, or bradykinesia).
• Disease duration of 4 years or more.
• Participant has elected to undergo DBS surgery as part of routine care, and the subthalamic nucleus (STN) is recommended as the surgical target.
• Participant agrees to not undergo contralateral DBS for the other side of the brain until ≥ 12 months after initial DBS surgery.
• Participant is healthy enough to undergo surgery and the research protocol.
• Normal, or essentially normal, preoperative brain MRI.
• Willingness and ability to cooperate during awake DBS surgery, as well as during post-operative evaluations, adjustments of medications and stimulator settings.
• Participant's health insurance and/or Medicare covers DBS surgery as part of routine care.
• Refractory motor symptoms such as tremor, dyskinesias, wearing off, and/or motor fluctuations, causing significant disability or occupational dysfunction, despite reasonable attempts at medical management, as determined by our consensus DBS committee.
• Stable doses of PD medications for at least 28 days prior to baseline assessments.
• Improvement of motor signs ≥30% with dopaminergic medication as assessed with the use of the Movement Disorders - Unified Parkinson's Disease Rating Scale, part III (MDS-UPDRS III; scores range from 0 to 108, with higher scores indicating worse functioning).
• Disease severity ratings above Hoehn and Yahr stage 1, defined as unilateral involvement only with minimal or no functional disability, with scores ranging from 0 to 5 and higher scores indicating more severe disease.
• Score of more than 6 for activities of daily living in the worst "off" medication condition despite medical treatment, as assessed with the use of the MDS-UPDRS II (scores range from 0 to 52, with higher scores indicating worse functioning), or mild-to-moderate impairment in social and occupational functioning (score of 51 to 80% on the Social and Occupational Functioning Assessment Scale with scores ranging from 1 to 100 and lower scores indicating worse functioning).
• Dementia Rating Scale-2 (DRS-2) score of ≥130 on medications.
• Beck Depression Inventory II (BDI-II) score of ≤25 on medications.
• Participant expresses understanding of the consent process, terms of the study protocol, is available for follow-up over the length of the study, and signs informed consent.

Exclusion Criteria

• Age 70 years.
• Participant's insurance will not cover the costs of surgery with the investigational device.
• Medical contraindications such as current uncontrolled hypertension, heart disease, coagulopathy, or other conditions contraindicating DBS surgery or stimulation.
• Duration of disease of 25 on the Beck Depression Inventory II, with scores ranging from 0 to 63 and higher scores indicating worse functioning), or history of suicide attempt.
• Any current acute psychosis, alcohol abuse or drug abuse.
• Clinical dementia (score of ≤130 on the Mattis Dementia Rating Scale with scores ranging from 0 to 144 and higher scores indicating better functioning).
• Ongoing or pervasive impulse control disorder not resolved by reduction of dopaminergic medications.
• Use of anticoagulant medications that cannot be discontinued during perioperative period.
• History of hemorrhagic stroke.
• Current or future risk of immunocompromise that might significantly increase risk of infection.
• History of recurrent of unprovoked seizures.
• Lack of clear levodopa responsiveness.
• Any medical condition requiring repeated MRI.
• The presence of an implanted device (e.g., cochlear implant, pacemaker, neurostimulators), whether turned on or off.
• Prior DBS surgery or ablation within the affected basal ganglion.
• A condition requiring or likely to require the use of diathermy.
• Structural lesions such as basal ganglioni