Non-invasive Brain Mapping for Parkinson's Disease

Overseen By Katy Cross, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, Los Angeles

Disqualifiers: Dementia, Hallucinations, Psychosis, MRI contraindications

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

90 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Movement task, DBS for Parkinson's Disease?

Research shows that deep brain stimulation (DBS) in the subthalamic nucleus (STN) can improve motor symptoms in Parkinson's disease by reducing abnormal brain activity and normalizing brain activation patterns during movement. Additionally, accurate placement of DBS electrodes, aided by advanced computer vision techniques, enhances treatment effectiveness by optimizing surgical targeting. ^{1 2 3 4 5}

Is non-invasive brain mapping for Parkinson's disease safe?

Research on deep brain stimulation (DBS), which is related to non-invasive brain mapping, shows that it is generally safe for humans. Studies involving MRI scans on patients with DBS devices found no short- or long-term adverse effects, and any side effects from DBS are linked to specific brain connections rather than the procedure itself. ^{6 7 8 9 10}

How does the treatment Movement task (DBS) for Parkinson's disease differ from other treatments?

The Movement task treatment, also known as deep brain stimulation (DBS), is unique because it involves implanting electrodes in the brain to send electrical impulses to specific areas, reducing abnormal brain activity associated with Parkinson's disease. Unlike medications, which are taken orally, DBS directly targets brain regions to improve motor symptoms and can be adjusted for optimal effectiveness. ^{2 3 11 12 13}

What is the purpose of this trial?

Several strategies or contexts help patients with Parkinson's disease to move more quickly or normally, however the brain mechanisms underlying these phenomena are poorly understood. The proposed studies use complimentary brain mapping techniques to understand the brain mechanisms supporting improved movements elicited by external cues. The central hypothesis is that distinct networks are involved in movement improvement depending on characteristics of the facilitating stimulus. Participants will perform movement tasks during recording of brain activity with EEG and MRI. The identified biomarkers may provide targets for future neuromodulation therapies to improve symptoms that are refractory to current treatments, such as freezing of gait.

Eligibility Criteria

This trial is for adults over 18 with Parkinson's disease, showing at least two main symptoms: tremor, stiffness or slow movement. Healthy adults without neurological diseases can also join. People with dementia, active hallucinations, psychosis or who cannot undergo MRI due to metal implants or claustrophobia are excluded.

Inclusion Criteria

I am older than 18 years.

I am a healthy adult without any brain or nerve diseases.

I have Parkinson's with at least 2 main symptoms or I am healthy with no brain disorders.

Exclusion Criteria

Contraindications to MRI (metal implant, claustrophobia)

You have a score lower than 19 on a test that checks for memory and thinking skills.

I am currently experiencing hallucinations or psychosis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Experimental Sessions

Participants perform movement tasks during EEG and MRI recording sessions

2 sessions, each lasting about 1.5 hours

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after experimental sessions

up to 4 weeks

Treatment Details

Interventions

• Movement task

Trial Overview The study investigates how certain stimuli facilitate movement in Parkinson's patients by using brain mapping techniques like EEG and MRI during movement tasks. The goal is to understand the brain networks that improve motion which could lead to new treatments.

Participant Groups

Group I: Parkinson disease patients Experimental Treatment 1 Intervention

Participants diagnosed with Parkinson's disease

Group II: Healthy adults Active Control 1 Intervention

Healthy adult age-matched controls

Movement task is already approved in United States for the following indications:

Approved in United States as DBS for:

• Parkinson's disease (tremor, advanced symptoms, earlier stages with motor symptoms not adequately controlled with medication)
• Essential tremor
• Multiple sclerosis

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Findings from Research

The study identified a specific 'sweet spot' in the subthalamic nucleus (STN) that is associated with significant motor improvement in Parkinson's disease patients, based on an analysis of 449 deep brain stimulation (DBS) settings across 21 patients.

Overlap of DBS stimulation with this sweet spot explained 37% of the variance in acute motor improvement, which is significantly higher than the 9% explained by general STN overlap, indicating that targeting this area could enhance the effectiveness of DBS programming.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probabilistic sweet spots predict motor outcome for deep brain stimulation in Parkinson disease. Dembek, TA., Roediger, J., Horn, A., et al.[2020]

A new deep learning-based computer vision method was successfully used to track and analyze motor behaviors in 5 patients undergoing deep brain stimulation (DBS) surgery for Parkinson's disease, achieving over 80% accuracy in automated assessments.

This innovative approach improves the accuracy and objectivity of motor testing during DBS procedures, potentially making neuro-motor mapping more accessible and effective, especially in resource-limited settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Automatic extraction of upper-limb kinematic activity using deep learning-based markerless tracking during deep brain stimulation implantation for Parkinson's disease: A proof of concept study. Baker, S., Tekriwal, A., Felsen, G., et al.[2023]

Deep brain stimulation (DBS) in patients with advanced Parkinson's disease significantly reduces abnormal brain activity in the motor system, which correlates with improvements in motor symptoms.

Functional brain imaging reveals that DBS not only affects the targeted area but also influences remote brain regions, indicating its complex role in modulating both motor and cognitive functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Functional imaging of deep brain stimulation in idiopathic Parkinson's disease]. Hilker, R.[2021]

In a study involving 6 patients with Parkinson's disease, therapeutic deep brain stimulation (DBS) of the subthalamic nucleus normalized brain activation patterns during movement, particularly increasing activity in areas like the supplementary motor area and cerebellum.

Effective DBS not only improved movement execution but also reduced compensatory overactivity in various brain regions, suggesting a more efficient motor control system in patients with Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Normalizing motor-related brain activity: subthalamic nucleus stimulation in Parkinson disease. Grafton, ST., Turner, RS., Desmurget, M., et al.[2021]

In a study of 57 Parkinson's disease patients who underwent bilateral STN-DBS, motor symptoms improved significantly by an average of 55.4% after 6 months, indicating the efficacy of this treatment.

The effectiveness of STN-DBS in improving motor symptoms is positively correlated with the proximity of the stimulation to the dorsolateral sensorimotor area of the STN, suggesting that precise targeting of this area enhances therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship between electrode position of deep brain stimulation and motor symptoms of Parkinson's disease. Zhang, F., Wang, F., Li, W., et al.[2021]

In a study of 102 participants with active deep brain stimulation (DBS) systems, no short- or long-term adverse events were reported during MRI scans at both 1.5 T and 3 T, indicating that DBS patients can safely undergo MRI procedures.

While DBS hardware caused some imaging artifacts, these only obscured a small portion of the brain (1.4% at 1.5 T and 2.1% at 3 T), primarily affecting areas near the electrode contacts, which suggests that MRI can still provide useful information in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional MRI Safety and Artifacts during Deep Brain Stimulation: Experience in 102 Patients. Boutet, A., Rashid, T., Hancu, I., et al.[2020]

In a study of 319 patients treated with deep brain stimulation (DBS) for various movement disorders over a 10-year period, the procedure demonstrated a favorable safety profile with rare intraoperative adverse events, such as vasovagal response (2.5%) and syncope (1.2%).

Long-term complications were also relatively low, with persistent issues like dysarthria and cognitive dysfunction occurring in about 4% of patients, indicating that DBS is a safe option for treating medically refractory movement disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term and long-term safety of deep brain stimulation in the treatment of movement disorders. Kenney, C., Simpson, R., Hunter, C., et al.[2022]

A survey of 40 out of 42 NPF Centers of Excellence found that 58% currently perform brain MRI on Parkinson's disease patients with DBS implants, indicating a growing acceptance of MRI use despite previous safety concerns.

Among 3304 patients who underwent brain MRI, only one case of implantable pulse generator (IPG) failure was reported, with no serious complications, suggesting a favorable risk/benefit ratio for MRI in DBS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of MRI in patients with implanted deep brain stimulation devices. Tagliati, M., Jankovic, J., Pagan, F., et al.[2015]

A study using the Deep Brain Stimulation Brain Tissue Network's database found no adverse clinical or pathological effects from performing 1.5 T MRI scans on patients with implanted DBS devices, suggesting that MRI is relatively safe for these patients.

Further examination of post-mortem brains with DBS leads exposed to prolonged 3T MRI also showed no evidence of heat-related damage, supporting the safety of higher field strength MRI in DBS patients under current guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of human brain tissue post-magnetic resonance imaging: information from the National Deep Brain Stimulation Brain Tissue Network (DBS-BTN). Ullman, M., Vedam-Mai, V., Krock, N., et al.[2011]

In a study of 21 Parkinson's disease patients with bilateral subthalamic deep brain stimulation (DBS), specific connectivity patterns of electrode contacts were linked to different stimulation-induced side effects, such as dysarthria and hyperkinesia.

The findings suggest that rather than just the location of the electrodes, the structural connectivity of the contacts plays a crucial role in determining side effects, indicating that a connectivity-based approach to target planning in DBS could enhance treatment outcomes and minimize adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Structural Connectivity Patterns of Side Effects Induced by Subthalamic Deep Brain Stimulation for Parkinson's Disease. Strotzer, QD., Kohl, Z., Anthofer, JM., et al.[2022]

In a study of 31 Parkinson's disease patients, researchers found that tremor and bradykinesia have nearly opposite neural signatures, which could help in monitoring disease progression and assessing treatment effectiveness.

Cortical activity provided better decoding of motor states than subcortical activity, suggesting that targeting specific brain regions, like the subthalamic nucleus, could enhance treatment strategies for managing Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent decoding of distinct neurophysiological fingerprints of tremor and bradykinesia in Parkinson's disease. Lauro, PM., Lee, S., Amaya, DE., et al.[2023]

In a study involving 11 Parkinson's disease patients, researchers found that using electrocorticography (ECoG) for brain signal decoding was more effective than subthalamic local field potentials (LFP) in predicting grip-force, which is important for movement control.

The study also revealed that the performance of ECoG-based decoding was negatively affected by the patients' motor impairments, suggesting that the underlying pathophysiology of Parkinson's disease influences how well the brain can encode movement, which is crucial for developing personalized brain-computer interfaces.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrocorticography is superior to subthalamic local field potentials for movement decoding in Parkinson's disease. Merk, T., Peterson, V., Lipski, WJ., et al.[2022]

Deep brain stimulation (DBS) of the subthalamic nucleus can help reduce symptoms of advanced Parkinson's disease, but the exact mechanism of how it works is still not fully understood.

A new MRI-based model has been developed to analyze the electric fields generated by DBS, showing that increasing the distance between electrodes can significantly reduce the stimulation effect, which is crucial for optimizing treatment settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A computational model for bipolar deep brain stimulation of the subthalamic nucleus. Iacono, MI., Neufeld, E., Bonmassar, G., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Probabilistic sweet spots predict motor outcome for deep brain stimulation in Parkinson disease. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Automatic extraction of upper-limb kinematic activity using deep learning-based markerless tracking during deep brain stimulation implantation for Parkinson's disease: A proof of concept study. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

[Functional imaging of deep brain stimulation in idiopathic Parkinson's disease]. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Normalizing motor-related brain activity: subthalamic nucleus stimulation in Parkinson disease. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Relationship between electrode position of deep brain stimulation and motor symptoms of Parkinson's disease. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Functional MRI Safety and Artifacts during Deep Brain Stimulation: Experience in 102 Patients. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Short-term and long-term safety of deep brain stimulation in the treatment of movement disorders. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Safety of MRI in patients with implanted deep brain stimulation devices. [2015]

9. United States pubmed.ncbi.nlm.nih.gov

A pilot study of human brain tissue post-magnetic resonance imaging: information from the National Deep Brain Stimulation Brain Tissue Network (DBS-BTN). [2011]

10. United States pubmed.ncbi.nlm.nih.gov

Structural Connectivity Patterns of Side Effects Induced by Subthalamic Deep Brain Stimulation for Parkinson's Disease. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Concurrent decoding of distinct neurophysiological fingerprints of tremor and bradykinesia in Parkinson's disease. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Electrocorticography is superior to subthalamic local field potentials for movement decoding in Parkinson's disease. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

A computational model for bipolar deep brain stimulation of the subthalamic nucleus. [2020]