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

Study Overview
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Brief Summary
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The purpose of the study is to determine whether new deep brain stimulation (DBS) device technologies can generate and record brain rhythms to reveal the best location for clinical stimulation.

Detailed Description
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The investigator's goal is to better understand how deep brain stimulation (DBS) modifies local neuronal activity and to pioneer device technologies that can record local DBS-evoked potentials (DLEPs) to guide therapy. Together, Neuromodulation eXperiment Testbed system (NEXT) with a novel 16-contact directional lead (Argyle) are uniquely suited for these purposes. The investigator's vision is for NEXT to guide both electrode targeting during surgery and programming in clinic, eventually as an integrated component of the implanted pulse generator. The results will inform directional DBS for PD and serve as a model for translation to other diseases where knowledge on DBS circuit interactions is at an even earlier stage.

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

Conditions
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Parkinson Disease

Intervention / Treatment
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* Device: Neuromodulation eXperiment Testbed system (NEXT) stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years and older Clinically definite, advanced idiopathic PD based on at least 2 of 3 cardinal PD features Disease duration of 4 years or more Participant has elected to undergo awake DBS surgery as part of routine care, and the subthalamic nucleus (STN) or globus pallidus interna (GPi) are recommended by the multidisciplinary DBS committee as the surgical target. Participant is healthy enough to undergo surgery and the research protocol Normal, or essentially normal, preoperative brain MRI, except for expected mild abnormalities associated with advanced PD 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 tremors, 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 as performed at baseline visit 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 as performed at baseline visit. 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, or mild-to-moderate impairment in social and occupational functioning as performed at baseline visit Dementia Rating Scale-2 score of ≥130 on medications from routine care record review Beck Depression Inventory II score of ≤25 on medications as performed at baseline visit 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 <18 years Participant's insurance will not cover the costs of surgery with an investigational device (Future exclusion for pending Aims 2 and 3 only) Medical contraindications such as current uncontrolled hypertension, heart disease, coagulopathy, or other conditions contraindicating DBS surgery or stimulation Duration of disease of <4 years Diagnosis or suspicion of atypical parkinsonism or drug-induced parkinsonism, or significant neurological disease other than Parkinson's disease Diagnosis of psychogenic movement disorder based on consensus criteria Patient is undergoing DBS electrode placement under general anesthesia without awake electrophysiological and clinical testing during implant Score of >25 on the Beck Depression Inventory II or history of suicide attempt Any current acute psychosis, alcohol abuse or drug abuse Clinical dementia 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 infection risk History of recurrent of unprovoked seizures Lack of clear levodopa responsiveness The presence of an implanted device whether turned on or off. Prior DBS surgery or ablation within the affected basal ganglion Prior DBS surgery on the opposite side of the brain (future pending Aims 2 and 3 only) A condition requiring or likely to require the use of diathermy Structural lesions such as basal ganglionic stroke, tumor, or vascular malformation as etiology of the movement disorder Any medical or psychological problem that would interfere with completing the study protocol, as determined by the research team A female who is breastfeeding or of child-bearing potential with a positive urine pregnancy test

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Device Feasibility
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aim 1 -<br>Elicit and measure interactions between DBS and target neuronal populations | Device: Neuromodulation eXperiment Testbed system (NEXT) stimulation<br>* Initial studies in this aim will use NEXT to stimulate and record neural activity at clinically effective sites.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Validate the biological origin of brain signals using the Neuromodulation eXperiment Testbed (NEXT) system during standard of care Deep Brain Stimulation surgery, both awake and under general anesthesia. | The investigator will validate the biological origin of the signals using pairs of DBS pulses and neural refractoriness with the NEXT System at therapeutically relevant stimulus amplitudes (i.e., inside and outside the therapeutic window). | At standard of care DBS surgery (awake) and approximately one week later at standard of care battery placement (under general anesthesia). | 
| Test whether a novel 16-contact DBS lead elicits spatiotemporally distinct oscillations in subthalamic nucleus versus globus pallidus interna. | This investigators efforts will yield granular spatial maps of neural engagement across the two canonical targets for PD to guide targeting (awake or under anesthesia) and clinical programming. | At standard of care DBS surgery (awake) and approximately one week later at standard of care battery placement (under general anesthesia). | 
| Test whether spatial maps of DBS-evoked oscillations predict clinically effective stimulation sites on the 16-contact lead. | The investigator will test whether spatial maps of DBS-evoked neural activity predict clinically effective locations for directional DBS on the 16-contact lead. | At standard of care DBS surgery (awake), approximately one week later at standard of care battery placement (under general anesthesia), at in a research clinical assessment at 6 months after DBS surgery. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DBS, Parkinson's Disease, Deep Brain Stimulation