Optimizing Adaptive DBS for Parkinson's Disease

Optimizing Adaptive Deep Brain Stimulation for Parkinson's Disease

Parkinson's disease (PD) affects more than 10 million people worldwide and causes progressive motor symptoms such as slowness, stiffness and tremor. For patients whose symptoms are no longer adequately controlled with medication, deep brain stimulation (DBS) can substantially improve motor function. More recently, adaptive DBS (aDBS) has become available. Unlike conventional DBS, which delivers continuous stimulation, aDBS automatically adjusts stimulation in response to brain activity recorded by the implanted device.

Current clinical aDBS programming is based primarily on brief recordings obtained during clinic visits. However, Parkinson's symptoms and the underlying brain signals change throughout the day in response to medication, daily activities and other factors. As a result, recordings collected during a single clinic visit may not fully capture the neural activity that best reflects a patient's symptoms in everyday life.

The purpose of this study is to determine whether incorporating long-term brain recordings collected during daily life improves adaptive DBS programming and clinical outcomes. Participants will first undergo in-clinic testing to identify brain signals associated with their symptoms. Brain activity and symptoms will then be monitored during everyday life using the sensing capabilities of the implanted DBS device. Participants with suitable brain signals will enter a randomized, blinded crossover study comparing three stimulation approaches: conventional continuous DBS, adaptive DBS programmed using the current clinic-based approach and adaptive DBS programmed using both clinic and at-home recordings.

The study will compare the effects of these approaches on motor fluctuations and quality of life. It will also determine how frequently different brain signals occur in people with Parkinson's disease and how well they reflect motor symptoms, providing information that may improve future adaptive DBS therapies.

Adaptive deep brain stimulation (aDBS) automatically adjusts stimulation based on brain activity recorded by an implanted deep brain stimulation (DBS) system. Current clinical programming of aDBS relies on recordings of brain activity collected during brief clinic visits. However, Parkinson's disease symptoms and the underlying brain activity fluctuate throughout the day in response to medication, daily activities and other factors. It is unknown whether recordings collected during routine clinic visits adequately capture the brain signals needed to optimize adaptive DBS for everyday life.

Commercially available sensing-enabled DBS systems now allow chronic recording of brain activity during everyday life. These recordings provide an opportunity to characterize patient-specific brain signals under real-world conditions and determine whether incorporating this information improves adaptive DBS programming and clinical outcomes.

This study addresses two primary questions:

1. Does more comprehensive in-clinic characterization of brain signals across medication states improve adaptive DBS programming compared with the current clinic-based approach?
2. Does incorporating chronic at-home recordings of brain activity further improve adaptive DBS programming and clinical outcomes?

The study consists of two sequential parts.

Part 1: Brain signal characterization and adaptive DBS programming

All enrolled participants will undergo comprehensive in-clinic testing across medication and stimulation states using a commercially available sensing-enabled DBS system. Brain activity will subsequently be recorded during everyday life using the device's chronic sensing capabilities together with participant-reported symptoms. These data will be used to identify patient-specific brain signals associated with medication state and motor symptoms and to develop individualized, data-driven adaptive DBS settings. Participants with brain signals that track their motor symptoms will be eligible for Part 2.

Part 2: Randomized crossover comparison of adaptive DBS programming strategies

Eligible participants will enter a randomized, blinded, within-subject crossover study comparing three stimulation approaches:

1. Conventional DBS with a fixed amplitude (cDBS)
2. Adaptive DBS programmed using the current clinic-based optimization procedure (aDBS-Standard)
3. Adaptive DBS programmed using an extended optimization procedure that combines comprehensive in-clinic characterization with chronic at-home recordings of brain activity (aDBS-Extended)

During the crossover phase, participants will wear a smartwatch to continuously monitor motor function and complete daily symptom and quality-of-life assessments using a smartphone application while continuing their usual daily activities. These measures will be used to compare the three stimulation approaches under real-world conditions.

This study will determine whether incorporating comprehensive in-clinic characterization and chronic at-home recordings of brain activity into adaptive DBS programming improves clinical outcomes compared with current programming methods. It will also characterize the prevalence and clinical relevance of brain signals used for adaptive DBS and provide information to guide future programming strategies for Parkinson's disease.

Inclusion Criteria:

• Subjects will be 18 and over
• Clinical diagnosis of idiopathic Parkinson's disease (PD), consistent with MDS diagnostic criteria
• Motor fluctuations in response to medication
• Bilateral subthalamic nucleus (STN) DBS using a commercial sensing-enabled device
• Stable cDBS settings for ≥3 months prior to enrollment
• Stable antiparkinsonian medication regimen for ≥4 weeks prior to enrollment
• Capacity to provide informed consent
• Ability and willingness to complete study visits and at-home monitoring
• For Part 2: Presence of an adequate STN neural signal (e.g., stable LFP feature suitable for biomarker extraction) during screening
• Ability to speak and understand English sufficiently to provide informed consent and complete study procedures and assessments without an interpreter.

Exclusion Criteria:

• Atypical or secondary parkinsonism (e.g., multiple system atrophy, progressive supranuclear palsy, vascular parkinsonism)
• Prior brain surgery other than STN DBS
• Clinically significant cognitive impairment or dementia, defined as MoCA < 24 or equivalent, or lacking capacity to provide informed consent
• Active psychiatric illness that could compromise safety or participation (e.g., uncontrolled depression, psychosis, severe anxiety disorder)
• History of suicidality or suicide attempt within the past year
• Clinically unstable medical conditions (e.g., uncontrolled hypertension, advanced cardiac or pulmonary disease) that would increase study risk
• Current substance abuse or dependence
• Ongoing participation in another interventional trial that could confound outcomes
• Pregnancy or plans to become pregnant during the study period
• Inability or unwillingness to comply with study procedures (e.g., at-home monitoring, study visits, data collection)