Cortical Electrophysiology of Response Inhibition in Parkinson's Disease

NCT06234995 | Recruiting Phase 4 FDA Drug FDA Device

• 3 other identifiers: STUDY00007291P50NS1231032025P008808
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

Brief Summary

Patients with Parkinson's Disease will be studied before, during, and after a deep brain stimulation implantation procedure to see if the stimulation location and the size of the electrical field produced by subthalamic nucleus (STN) DBS determine the degree to which DBS engages circuits that involve prefrontal cortex executive functions, and therefore have a direct impact on the patient's ability to inhibit actions.

Conditions

Parkinson Disease

Keywords

Parkinson's Disease; Deep brain stimulation

Outcome Measures

Primary Outcomes (6)

• Response Time During Go/No-Go (GNG) Task for Participants in Aim 1

  The GNG task is a tool for measuring impulsiveness by asking participants to respond to a cue signal for pressing a button. There are Go trials, where the button should be pressed, and No-Go trials, where the button should not be pressed. A total of 240 trials will be administered (5 blocks of 30) after an initial practice block (12 trials). An additional 120 Go only trials will be administered prior to the Go/No-Go blocks and serve as a control without inhibitory demands. Participants with PD attend a single study visit, completing this task twice: once after not taking PD medications for 12 hours and again after levodopa dosage. Healthy controls complete the task twice during one study visit. Response time is measured in milliseconds (ms) during the GNG task.

  Day 1 (before and after levodopa dosage for persons with PD)

• Percent of Errors During Go/No-Go (GNG) Task for Participants in Aim 1

  The GNG task is a tool for measuring impulsiveness by asking participants to respond to a cue signal for pressing a button. There are Go trials, where the button should be pressed, and No-Go trials, where the button should not be pressed. A total of 240 trials will be administered (5 blocks of 30) after an initial practice block (12 trials). An additional 120 Go only trials will be administered prior to the Go/No-Go blocks and serve as a control without inhibitory demands. Participants with PD attend a single study visit, completing this task twice: once after not taking PD medications for 12 hours and again after levodopa dosage. Healthy controls complete the task twice during one study visit. Accuracy is measured as the percentage of errors during the GNG task.

  Day 1 (before and after levodopa dosage for persons with PD)

• Stopping Time During Modified Stop Signal (MSS) Task for Participants in Aim 1

  For the MSS task, a fixation cross indicates the start of a trial. After a variable delay (300-700 ms) this signal is replaced by a green Go signal circle, prompting the subject to start to make circling movements with a computer mouse at approximately one rotation per second using dominant hand. After 500 ms the green circle is replaced by a visual countdown to when a red Stop signal appears (planned stop). In 50% of the trials, the Stop signal appears unexpectedly during the countdown (unplanned stop). A total of 120 trials will be administered (10 blocks of 12). Participants with PD attend a single study visit, completing this task twice: once after not taking PD medications for 12 hours and again after levodopa dosage. Healthy controls complete the task twice during one study visit. Stopping time is measured in milliseconds.

  Day 1 (before and after levodopa dosage for persons with PD)

• Response Time During Go/No-Go (GNG) Task for Participants in Aim 3

  The GNG task is a tool for measuring impulsiveness by asking participants to respond to a cue signal for pressing a button. There are Go trials, where the button should be pressed, and No-Go trials, where the button should not be pressed. A total of 240 trials will be administered (5 blocks of 30) after an initial practice block (12 trials). An additional 120 Go only trials will be administered prior to the Go/No-Go blocks and serve as a control without inhibitory demands. Participants with PD attend two study visits, within a 4-week period, at 6 to 12 months after implantation of the DBS leads. Participants will not take PD medications for 12 hours prior to the study visit. During each study visit chronic DBS will be turned off and two stimulation settings will be tested at each study visit so that participants all four stimulation settings over the two study visits. Response time is measured in milliseconds (ms) during the GNG task.

  Up to 12 months post-implantation of DBS leads

• Percent of Errors During Go/No-Go (GNG) Task for Participants in Aim 3

  The GNG task is a tool for measuring impulsiveness by asking participants to respond to a cue signal for pressing a button. There are Go trials, where the button should be pressed, and No-Go trials, where the button should not be pressed. A total of 240 trials will be administered (5 blocks of 30) after an initial practice block (12 trials). An additional 120 Go only trials will be administered prior to the Go/No-Go blocks and serve as a control without inhibitory demands. Participants with PD attend two study visits, within a 4-week period, at 6 to 12 months after implantation of the DBS leads. Participants will not take PD medications for 12 hours prior to the study visit. During each study visit chronic DBS will be turned off and two stimulation settings will be tested at each study visit so that participants all four stimulation settings over the two study visits. Accuracy is measured as the percentage of errors during the GNG task.

  Up to 12 months post-implantation of DBS leads

• Stopping Time During Modified Stop Signal (MSS) Task for Participants in Aim 3

  For the MSS task, a fixation cross indicates the start of a trial. After a variable delay (300-700 ms) this signal is replaced by a green Go signal circle, prompting the subject to start to make circling movements with a computer mouse at approximately one rotation per second using dominant hand. After 500 ms the green circle is replaced by a visual countdown to when a red Stop signal appears (planned stop). In 50% of the trials, the Stop signal appears unexpectedly during the countdown (unplanned stop). A total of 120 trials will be administered. Participants with PD attend two study visits, within a 4-week period, at 6 to 12 months after implantation of the DBS leads. Participants will not take PD medications for 12 hours prior to the study visit. During each visit chronic DBS will be turned off and two stimulation settings will be tested so that participants all four stimulation settings over the two study visits. Stopping time is measured in milliseconds.

  Up to 12 months post-implantation of DBS leads

Secondary Outcomes (5)

• Electroencephalogram (EEG) Signals During GNG for Participants in Aim 1

  Day 1 (before and after levodopa dosage for persons with PD)

• Electroencephalogram (EEG) Signals During MSS for Participants in Aim 1

  Day 1 (before and after levodopa dosage for persons with PD)

• Electrocorticography (ECoG) Signals During GNG for Participants in Aim 2

  During surgical procedure to implant clinically-indicated DBS leads (approximately 15 minutes on the single day of surgery)

• Electroencephalogram (EEG) Signals During GNG for Participants in Aim 3

  Up to 12 months post-implantation of DBS leads

• Electroencephalogram (EEG) Signals During MSS for Participants in Aim 3

  Up to 12 months post-implantation of DBS leads

Study Arms (2)

Patients with Parkinson's Disease (PD)

EXPERIMENTAL

Patients with PD complete motor response inhibitions tasks under multiple conditions, depending on the study aim they are participating in. Those who are participants in Aim 1 of the study are able to also participate in Aims 2 and 3 if they are having a clinically indicated DBS leads implanted. Patients with PD participate in the study for approximately 18 months which includes one preoperative visit, intraoperative data collection and two post-operative visits. As part of the motor inhibition tasks, EEG signals are recorded. A cap similar to a swim cap is placed on the head of the subject, and gel is applied to the hair to get a good signal. Electrodes are attached to the cap for recording of brain signals. A few additional flat electrodes are placed on the skin to record hand muscle activity (for GNG task) and near the eyes to record eye movements. Accelerometer sensors are utilized to record arm movements (for MSS task).

Drug: Levodopa; Device: Clinical DBS Setting; Device: Sham DBS; Device: DBS Setting Maximizing Prefrontal Activation; Device: DBS Setting Minimizing Prefrontal Activation

Healthy Controls

NO INTERVENTION

Healthy participants complete motor response inhibition tasks during two study visits. Healthy controls participate for approximately one month, which includes two study visits. As part of the motor inhibition tasks, EEG signals are recorded. A cap similar to a swim cap is placed on the head of the subject, and gel is applied to the hair to get a good signal. Electrodes are attached to the cap for recording of brain signals. A few additional flat electrodes are placed on the skin to record hand muscle activity (for GNG task) and near the eyes to record eye movements. Accelerometer sensors are utilized to record arm movements (for MSS task).

Interventions

Levodopa DRUG

Participants will take levodopa in dosages prescribed by their care provider. Patients will be instructed to not take their regularly prescribed PD medications for 12 hours prior to the study assessment, as is typical for clinical evaluations in patients with PD. Participants will be tested in both levodopa-off (after 12 hours of not having medication) and levodopa-on states.

Also known as: L-Dopa

Patients with Parkinson's Disease (PD)

Clinical DBS Setting DEVICE

Deep brain stimulation performed with the patients' optimized clinical setting.

Patients with Parkinson's Disease (PD)

Sham DBS DEVICE

Deep brain stimulation performed with sham stimulation.

Patients with Parkinson's Disease (PD)

DBS Setting Maximizing Prefrontal Activation DEVICE

Deep brain stimulation performed to maximize the activation of the prefrontal cortico-STN projections.

Patients with Parkinson's Disease (PD)

DBS Setting Minimizing Prefrontal Activation DEVICE

Deep brain stimulation performed to minimize the activation of the prefrontal cortico-STN projections.

Patients with Parkinson's Disease (PD)

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• diagnosis of idiopathic Parkinson's disease (PD)
• Hoehn and Yahr (H\&Y) stage 2-4 (off medication)

You may not qualify if:

• severe tremor at rest or severe dyskinesia which would cause significant artifacts in electrophysiological signals
• inability to hold antiparkinsonian medications for research recordings
• dementia
• non-English speaker
• diagnosis of idiopathic PD
• there is a clinical indication for DBS surgery
• normal preoperative MRI
• ability to tolerate microelectrode-guided neurosurgery in an awake state
• presence of a coagulopathy
• uncontrolled hypertension
• heart disease
• other medical conditions considered to increase the patient's risk for surgical complications
• diagnosis of idiopathic PD
• functioning DBS system
• severe tremor at rest or severe dyskinesia which would cause significant artifacts in electrophysiological signals

Sponsors & Collaborators

• Emory University: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (2)

Emory University Hospital

Atlanta, Georgia, 30322, United States

RECRUITING

Emory Brain Health Center

Atlanta, Georgia, 30329, United States

RECRUITING

MeSH Terms

Conditions

Parkinson Disease

Interventions

Levodopa

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Tyrosine

Study Officials

• Svjetlana Miocinovic, MD, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jonna Seppa

CONTACT

404-727-1509; jonna.k.seppa@emory.edu

Svjetlana Miocinovic, MD, PhD

CONTACT

404-712-9065

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: A motor exam will be performed and video recorded for blinded analysis by a movement disorders neurologist.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Healthy controls and persons with PD will be compared in Aim 1. In Aim 3, participants with PD, who have had DBS leads implanted will complete study assessments under four different DBS stimulation settings.

Study Record Dates

• First Submitted: January 23, 2024
• First Posted: January 31, 2024
• Study Start: August 9, 2021
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: Data will be available for sharing immediately following publication and ending 5 years following article publication.
• Access Criteria: Data will be available for sharing with researchers who wish to access the data, for any purpose. Requests should be directed to the corresponding author listed in the published journal article.

Locations

US (2)