Stimulus-Evoked Directional Field Potentials to Guide Subthalamic and Pallidal DBS for PD

Inclusion criteria:

1. Age >18 years and older.

2. Clinically definite, advanced idiopathic PD based on at least 2 of 3 cardinal PDfeatures (tremor, rigidity, and/or bradykinesia).

3. Disease duration of 4 years or more.

4. Participant has elected to undergo awake DBS surgery as part of routine care, andthe subthalamic nucleus (STN) or globus pallidus interna (GPi) are recommended bythe multidisciplinary DBS committee as the surgical target.

5. For participants who opt for the dual-target strategy, neurosurgery judges thatdual-target STN and GPi implant is an appropriate option with acceptable safetyprofile.

6. Participant is healthy enough to undergo surgery and the research protocol.

7. Normal, or essentially normal, preoperative brain MRI, except for expected mildabnormalities associated with advanced PD.

8. Willingness and ability to cooperate during awake DBS surgery, as well as duringpost-operative evaluations, adjustments of medications and stimulator settings.

9. Participant's health insurance and/or Medicare covers DBS surgery as part of routinecare.

10. Refractory motor symptoms such as dyskinesias, wearing off, and/or motorfluctuations, causing significant disability or occupational dysfunction, despitereasonable attempts at medical management, as determined by our consensus DBScommittee.

11. Stable doses of PD medications for at least 28 days prior to baseline assessments.

12. Improvement of motor signs ≥30% with dopaminergic medication as assessed with theuse 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 worsefunctioning). One exception to this 30% threshold is patients who have typicalfeatures of PD but cannot take levodopa because of unacceptable side effects.19

13. Disease severity ratings above Hoehn and Yahr stage 2.5, defined as unilateralinvolvement only with minimal or no functional disability, with scores ranging from 0 to 5 and higher scores indicating more severe disease.

14. Score of more than 6 for activities of daily living in the worst "off" medicationcondition 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), ormild-to-moderate impairment in social and occupational functioning (score of 51 to 80% on the Social and Occupational Functioning Assessment Scale with scores rangingfrom 1 to 100 and lower scores indicating worse functioning).

15. Dementia Rating Scale-2 (DRS-2) score of ≥130 on medications.

16. Beck Depression Inventory II (BDI-II) score of ≤25 on medications.

17. No indication of suicidal ideation or active suicidal thoughts as assessed by theColumbia-Suicide Severity Rating Scale (C-SSRC).

18. Participant expresses understanding of the consent process, terms of the studyprotocol, is available for follow-up over the length of the study, and signsinformed consent.

Exclusion criteria:

1. Age <18 years.

2. Participant's insurance will not cover the costs of surgery with an investigationaldevice (Aims 2 and 3 only).

3. Medical contraindications such as current uncontrolled hypertension, heart disease,coagulopathy, or other conditions contraindicating DBS surgery or stimulation.

4. Duration of disease of <4 years

5. Clinical team suspects patient will need staged contralateral DBS for clinicalsymptoms within 1 year of unilateral DBS surgery.

6. Diagnosis or suspicion of atypical parkinsonism (progressive supranuclear palsy,multiple system atrophy, corticobasal syndrome) or drug-induced parkinsonism, orsignificant neurological disease other than Parkinson's disease.

7. Diagnosis of psychogenic movement disorder based on consensus criteria.

8. Dual-target implant cannot be performed safely from a single burr hole because ofanatomic constraints or cortical vascular anatomy, based upon the pre-operativeneurosurgery plan.

9. Patient is undergoing DBS electrode placement under general anesthesia without awakeelectrophysiological and clinical testing during implant.

10. Score of >25 on the Beck Depression Inventory II, with scores ranging from 0 to 63and higher scores indicating worse functioning), or history of suicide attempt.

11. An indication of suicidal ideation or active suicide planning as assessed on theColumbia-Suicide Severity Rating Scale.

12. Any current acute psychosis, alcohol abuse or drug abuse.

13. Clinical dementia (score of ≤130 on the Mattis Dementia Rating Scale with scoresranging from 0 to 144 and higher scores indicating better functioning).

14. Ongoing or pervasive impulse control disorder not resolved by reduction ofdopaminergic medications.

15. Use of anticoagulant medications that cannot be discontinued during perioperativeperiod.

16. History of hemorrhagic stroke.

17. Current or future risk of immunocompromise that might increase infection risk.

18. History of recurrent of unprovoked seizures.

19. Lack of clear levodopa responsiveness.

20. The presence of an implanted device (e.g., cochlear implant, pacemaker,neurostimulators), whether turned on or off.

21. Prior DBS surgery or ablation within the affected basal ganglion.

22. Prior DBS surgery on the opposite side of the brain (Aims 2 and 3 only). This mayallow us to study some participants twice (i.e., in Aim 1 or 2-3, and again in Aim 1if they return for DBS on the opposite side of the brain as part of routine care).

23. A condition requiring or likely to require the use of diathermy.

24. Structural lesions such as basal ganglionic stroke, tumor, or vascular malformationas etiology of the movement disorder.

25. Any medical or psychological problem that would interfere with completing the studyprotocol, as determined by the research team.

26. A female who is breastfeeding or of child-bearing potential with a positive urinepregnancy test or not using adequate contraception.