Parkinson DiseasePhase 4NCT06234995
Cortical Electrophysiology of Response Inhibition in Parkinson's Disease
A Phase 4 study testing Levodopa, Clinical DBS Setting and DBS Setting Maximizing Prefrontal Activation in people with Parkinson Disease, run by Emory University at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 45 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Parkinson Disease
- What is being tested?
- Levodopa, Clinical DBS Setting and DBS Setting Maximizing Prefrontal Activation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 2 sitesUnited States
- Study dates
- 9 Aug 2021to Sep 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- age 45-75
Who cannot join
- history of a neuropsychiatric disorder and/or treatment with psychotropic medications
- non-English speaker
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Svjetlana Miocinovic, MD, PhD contact
United States2 sites, 2 recruiting
- Recruiting
Emory University Hospital
Atlanta, Georgia, 30322
- Recruiting
Emory Brain Health Center
Atlanta, Georgia, 30329
About this study
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.
Read the detailed description
Patients with Parkinson's disease (PD) commonly develop difficulties with executive function due to neurodegeneration in neuronal networks that involve the prefrontal cortex and associative territories of the basal ganglia, even in early stages of the disease. Executive cognitive functions serve to direct behavior toward a goal and modify actions to accommodate changing demands. One of the key components of executive control is the ability to cancel or inhibit habitual responses. Motor response inhibition is critical in everyday life, for example, to stop crossing the street when a speeding car appears. In patients with PD, the failure of these inhibitory control mechanisms may manifest, for example, as an inability to stop festinating gait or as impulsively jumping out of a chair and losing balance. Beyond the failure of stopping or inhibiting motor responses, patients with PD are also prone to impulsivity and compulsions, leading to behaviors such as overeating or gambling. Approximately 15-20% of PD patients are diagnosed with impulse control disorders which can be exacerbated by dopaminergic medications. Furthermore, PD patients with deep brain stimulation (DBS) may develop additional impairments in executive function. Given the prevalence of executive dysfunction, the everyday-importance of this issue, and the connection with PD therapies, disease- or therapy-induced alterations in inhibitory control are an important area of research in PD.
The primary clinical objective for DBS therapy in PD has been to optimize motor function. The effect of stimulation on cognition and behavior, particularly in the subthalamic nucleus (STN), has been controversial. Behavioral side effects have been supported by reports of worsened cognition, increased impulsivity and even suicidal behavior. While large, randomized trials do not show significant detrimental changes in global cognition with DBS, meta-analyses and systematic reviews have shown adverse effects on executive functions, particularly response inhibition. Based on animal studies, the STN can be divided into a sensorimotor (dorsolateral), cognitive-associative (ventromedial) and limbic (medial) parts. Most DBS leads implanted into the STN contain four ring-shaped contacts, spaced over a total distance of 7.5-10.5mm. While surgeons generally target the dorsolateral sensorimotor region of the STN, the most ventral DBS contacts almost inevitably end up in the ventral associative or limbic regions of the nucleus. There are anecdotal observations of abrupt mood and behavioral changes (impulsivity, hypomania, depression) with STN DBS, perhaps due to spread of stimulation to the ventral STN regions. However, the effect of stimulation location on cognitive function is poorly understood and unaccounted for in clinical programming which may lead to suboptimal gains in quality of life.
Electrophysiology and imaging studies have demonstrated that the STN is a key node in the inhibitory network, although other basal ganglia nuclei are involved. The STN receives input from prefrontal cortical areas (via the prefrontal hyperdirect pathway) and is thought to provide a global inhibitory signal to the basal ganglia and thalamus to halt habitual responses and allow additional processing time in situations of conflict and uncertainty. STN DBS might (antidromically) disrupt the inhibitory signal from the cortex, leading to impulsive responses and inability to inhibit actions. However, it remains unclear whether stimulation in the STN worsens or improves motor response inhibition. It is also possible that some aspects of inhibitory control (proactive vs. reactive) can worsen during stimulation while others improve suggesting that the effects may be mediated by different pathways or mechanisms. Proactive inhibition refers to preparatory mechanisms that facilitate action inhibition (i.e. enables a person to act with restraint), while reactive inhibition is a sudden stopping process triggered by an external stimulus.
This study will address the following knowledge gaps:
- Which cortical mechanisms (on the level of population-based electrophysiologic activity) are engaged in different aspects of inhibitory control (proactive control vs reactive; discrete movements vs continuous) in PD patients compared to healthy controls?
- Does the effect of STN DBS on motor response inhibition depend on activation of the prefrontal hyperdirect pathway?
Successful completion of the proposed studies will provide substantial new knowledge about the frontal brain areas involved in inhibitory control, their topographic representation within the STN and means of cortico-subcortical communication. The results may inform future DBS targeting and programming strategies, aiming to avoid cognitive side effects of STN DBS. Recent engineering upgrades to clinical devices (e.g. segmented leads) allow more precise fine tuning of the stimulation field which can serve to design stimulation strategies that maximize motor benefit and minimize cognitive and behavioral side effects.
This study will enroll patients with Parkinson's Disease as well as health controls. Participation in this trial does not affect patient's clinical management. Patients' medication (levodopa) dosages and decision to undergo deep brain stimulation surgery are based on clinical needs.
There are 3 study aims:
Aim 1: To determine the effect of the PD disease process, levodopa treatment, and cognitive status on performance and cortical electrophysiology during motor response inhibition tasks. Participants with PD prior to surgery to implant the DBS leads and healthy controls are examined in Aim 1.
Aim 2: To characterize cortico-subthalamic connectivity during proactive motor response inhibition during surgery to implant clinically-indicated DBS leads in participants with PD.
Aim 3: To determine if activation of the prefrontal cortico-STN hyperdirect pathway impairs response inhibition in participants with PD from Aim 1 after implantation of DBS leads.
The experimental interventions considered in this study are: 1) medication state (PD patients are tested in levodopa-off and levodopa-on state), and 2) DBS stimulation settings (PD patients are tested under 4 stimulation settings: clinical, sham, maximizing prefrontal activation, and minimizing prefrontal activation). Healthy controls will attend two study visits, while patients with PD will be in the study for up to 18 months.
- Conditions
- Parkinson Disease
- Being tested
- Levodopa, Clinical DBS Setting, Sham DBS, DBS Setting Maximizing Prefrontal Activation, DBS Setting Minimizing Prefrontal Activation
- Keywords
- Parkinson's Disease, Deep brain stimulation
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevodopaDrug
Also called L-Dopa
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.
Clinical DBS SettingDevice
Deep brain stimulation performed with the patients' optimized clinical setting.
Sham DBSDevice
Deep brain stimulation performed with sham stimulation.
DBS Setting Maximizing Prefrontal ActivationDevice
Deep brain stimulation performed to maximize the activation of the prefrontal cortico-STN projections.
DBS Setting Minimizing Prefrontal ActivationDevice
Deep brain stimulation performed to minimize the activation of the prefrontal cortico-STN projections.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 12 months post-implantation of DBS leads
Secondary outcomes (5)
Electroencephalogram (EEG) Signals During GNG for Participants in Aim 1
Cortical EEG signals are acquired simultaneously during GNG task. Trigger pulses are sent from the task computer to the EEG system indicating the stimulus onsets and subject responses (button press or mouse movement). A photodiode attached to the screen will monitor the timing of stimulus presentation synchronized to EEG.
Measured: Day 1 (before and after levodopa dosage for persons with PD)
Electroencephalogram (EEG) Signals During MSS for Participants in Aim 1
Cortical EEG signals are acquired simultaneously during the MSS task. Trigger pulses will be sent from the task computer to the EEG system indicating the stimulus onsets and subject responses (button press or mouse movement). The mouse spatial coordinates and data from a wrist accelerometer are recorded during the MSS task. A photodiode attached to the screen will monitor the timing of stimulus presentation synchronized to EEG.
Measured: Day 1 (before and after levodopa dosage for persons with PD)
Electrocorticography (ECoG) Signals During GNG for Participants in Aim 2
ECoG signals are recorded during interoperative administration of the GNG task. 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 photodiode is affixed to the screen to synchronize the electrophysiological recordings with stimulus onsets and, like the response button readout, inputs directly into the recording system.
Measured: 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
Cortical EEG signals are acquired simultaneously during GNG task. Trigger pulses are sent from the task computer to the EEG system indicating the stimulus onsets and subject responses (button press or mouse movement). A photodiode attached to the screen will monitor the timing of stimulus presentation synchronized to EEG.
Measured: Up to 12 months post-implantation of DBS leads
Electroencephalogram (EEG) Signals During MSS for Participants in Aim 3
Cortical EEG signals are acquired simultaneously during the MSS task. Trigger pulses will be sent from the task computer to the EEG system indicating the stimulus onsets and subject responses (button press or mouse movement). The mouse spatial coordinates and data from a wrist accelerometer are recorded during the MSS task. A photodiode attached to the screen will monitor the timing of stimulus presentation synchronized to EEG.
Measured: Up to 12 months post-implantation of DBS leads
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2024
- Study start9 Aug 2021
- Primary completionSep 2027 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Svjetlana Miocinovic, Emory University
- Investigators
- Svjetlana Miocinovic, MD, PhD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06234995
- Sponsor's protocol ID
- STUDY00007291
- Other IDs
- P50NS123103, 2025P008808
- Status last verified
- Aug 2026
- First submitted
- 23 Jan 2024
- Last updated
- 3 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: Individual participant data that underlie the results reported from this study will be made available for sharing with other researchers, after de-identification.
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cortical Electrophysiology of Response Inhibition in Parkinson's Disease
- ClinicalTrials.gov ID
- NCT06234995
- Acronym / sponsor ID
- STUDY00007291
- Conditions
- Parkinson Disease
- Keywords
- Parkinson's Disease, Deep brain stimulation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 9 Aug 2021 (actual)
- Primary completion
- Sep 2027 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 31 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Patients with Parkinson's disease (PD) commonly develop difficulties with executive function due to neurodegeneration in neuronal networks that involve the prefrontal cortex and associative territories of the basal ganglia, even in early stages of the disease. Executive cognitive functions serve to direct behavior toward a goal and modify actions to accommodate changing demands. One of the key components of executive control is the ability to cancel or inhibit habitual responses. Motor response inhibition is critical in everyday life, for example, to stop crossing the street when a speeding car appears. In patients with PD, the failure of these inhibitory control mechanisms may manifest, for example, as an inability to stop festinating gait or as impulsively jumping out of a chair and losing balance. Beyond the failure of stopping or inhibiting motor responses, patients with PD are also prone to impulsivity and compulsions, leading to behaviors such as overeating or gambling. Approximately 15-20% of PD patients are diagnosed with impulse control disorders which can be exacerbated by dopaminergic medications. Furthermore, PD patients with deep brain stimulation (DBS) may develop additional impairments in executive function. Given the prevalence of executive dysfunction, the everyday-importance of this issue, and the connection with PD therapies, disease- or therapy-induced alterations in inhibitory control are an important area of research in PD.
The primary clinical objective for DBS therapy in PD has been to optimize motor function. The effect of stimulation on cognition and behavior, particularly in the subthalamic nucleus (STN), has been controversial. Behavioral side effects have been supported by reports of worsened cognition, increased impulsivity and even suicidal behavior. While large, randomized trials do not show significant detrimental changes in global cognition with DBS, meta-analyses and systematic reviews have shown adverse effects on executive functions, particularly response inhibition. Based on animal studies, the STN can be divided into a sensorimotor (dorsolateral), cognitive-associative (ventromedial) and limbic (medial) parts. Most DBS leads implanted into the STN contain four ring-shaped contacts, spaced over a total distance of 7.5-10.5mm. While surgeons generally target the dorsolateral sensorimotor region of the STN, the most ventral DBS contacts almost inevitably end up in the ventral associative or limbic regions of the nucleus. There are anecdotal observations of abrupt mood and behavioral changes (impulsivity, hypomania, depression) with STN DBS, perhaps due to spread of stimulation to the ventral STN regions. However, the effect of stimulation location on cognitive function is poorly understood and unaccounted for in clinical programming which may lead to suboptimal gains in quality of life.
Electrophysiology and imaging studies have demonstrated that the STN is a key node in the inhibitory network, although other basal ganglia nuclei are involved. The STN receives input from prefrontal cortical areas (via the prefrontal hyperdirect pathway) and is thought to provide a global inhibitory signal to the basal ganglia and thalamus to halt habitual responses and allow additional processing time in situations of conflict and uncertainty. STN DBS might (antidromically) disrupt the inhibitory signal from the cortex, leading to impulsive responses and inability to inhibit actions. However, it remains unclear whether stimulation in the STN worsens or improves motor response inhibition. It is also possible that some aspects of inhibitory control (proactive vs. reactive) can worsen during stimulation while others improve suggesting that the effects may be mediated by different pathways or mechanisms. Proactive inhibition refers to preparatory mechanisms that facilitate action inhibition (i.e. enables a person to act with restraint), while reactive inhibition is a sudden stopping process triggered by an external stimulus.
This study will address the following knowledge gaps:
- Which cortical mechanisms (on the level of population-based electrophysiologic activity) are engaged in different aspects of inhibitory control (proactive control vs reactive; discrete movements vs continuous) in PD patients compared to healthy controls?
- Does the effect of STN DBS on motor response inhibition depend on activation of the prefrontal hyperdirect pathway?
Successful completion of the proposed studies will provide substantial new knowledge about the frontal brain areas involved in inhibitory control, their topographic representation within the STN and means of cortico-subcortical communication. The results may inform future DBS targeting and programming strategies, aiming to avoid cognitive side effects of STN DBS. Recent engineering upgrades to clinical devices (e.g. segmented leads) allow more precise fine tuning of the stimulation field which can serve to design stimulation strategies that maximize motor benefit and minimize cognitive and behavioral side effects.
This study will enroll patients with Parkinson's Disease as well as health controls. Participation in this trial does not affect patient's clinical management. Patients' medication (levodopa) dosages and decision to undergo deep brain stimulation surgery are based on clinical needs.
There are 3 study aims:
Aim 1: To determine the effect of the PD disease process, levodopa treatment, and cognitive status on performance and cortical electrophysiology during motor response inhibition tasks. Participants with PD prior to surgery to implant the DBS leads and healthy controls are examined in Aim 1.
Aim 2: To characterize cortico-subthalamic connectivity during proactive motor response inhibition during surgery to implant clinically-indicated DBS leads in participants with PD.
Aim 3: To determine if activation of the prefrontal cortico-STN hyperdirect pathway impairs response inhibition in participants with PD from Aim 1 after implantation of DBS leads.
The experimental interventions considered in this study are: 1) medication state (PD patients are tested in levodopa-off and levodopa-on state), and 2) DBS stimulation settings (PD patients are tested under 4 stimulation settings: clinical, sham, maximizing prefrontal activation, and minimizing prefrontal activation). Healthy controls will attend two study visits, while patients with PD will be in the study for up to 18 months.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Patients with Parkinson's Disease (PD) | Experimental | Drug: Levodopa, Device: Clinical DBS Setting, Device: Sham DBS, Device: DBS Setting Maximizing Prefrontal Activation, Device: DBS Setting Minimizing Prefrontal ActivationPatients 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). |
| 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). |
Who may qualify
- Ages
- 45 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- age 45-75
Key exclusion criteria (2 listed)
- history of a neuropsychiatric disorder and/or treatment with psychotropic medications
- non-English speaker
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LevodopaAlso: L-DopaParticipants 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. | Drug | Patients with Parkinson's Disease (PD) |
| Clinical DBS SettingDeep brain stimulation performed with the patients' optimized clinical setting. | Device | Patients with Parkinson's Disease (PD) |
| Sham DBSDeep brain stimulation performed with sham stimulation. | Device | Patients with Parkinson's Disease (PD) |
| DBS Setting Maximizing Prefrontal ActivationDeep brain stimulation performed to maximize the activation of the prefrontal cortico-STN projections. | Device | Patients with Parkinson's Disease (PD) |
| DBS Setting Minimizing Prefrontal ActivationDeep brain stimulation performed to minimize the activation of the prefrontal cortico-STN projections. | Device | Patients with Parkinson's Disease (PD) |
Primary outcome
Response Time During Go/No-Go (GNG) Task for Participants in Aim 1
Time frame: Day 1 (before and after levodopa dosage for persons with PD)
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.
Percent of Errors During Go/No-Go (GNG) Task for Participants in Aim 1
Time frame: Day 1 (before and after levodopa dosage for persons with PD)
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.
Stopping Time During Modified Stop Signal (MSS) Task for Participants in Aim 1
Time frame: Day 1 (before and after levodopa dosage for persons with PD)
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.
Response Time During Go/No-Go (GNG) Task for Participants in Aim 3
Time frame: Up to 12 months post-implantation of DBS leads
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.
Percent of Errors During Go/No-Go (GNG) Task for Participants in Aim 3
Time frame: Up to 12 months post-implantation of DBS leads
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.
Stopping Time During Modified Stop Signal (MSS) Task for Participants in Aim 3
Time frame: Up to 12 months post-implantation of DBS leads
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.
5 secondary outcomes
Electroencephalogram (EEG) Signals During GNG for Participants in Aim 1
Time frame: Day 1 (before and after levodopa dosage for persons with PD)
Electroencephalogram (EEG) Signals During MSS for Participants in Aim 1
Time frame: Day 1 (before and after levodopa dosage for persons with PD)
Electrocorticography (ECoG) Signals During GNG for Participants in Aim 2
Time frame: 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
Time frame: Up to 12 months post-implantation of DBS leads
Electroencephalogram (EEG) Signals During MSS for Participants in Aim 3
Time frame: Up to 12 months post-implantation of DBS leads
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2026.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported from this study will be made available for sharing with other researchers, after de-identification.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Svjetlana Miocinovic, MD, PhD contact
Svjetlana Miocinovic, MD, PhD principal investigator
Emory University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Levodopa, Clinical DBS Setting and DBS Setting Maximizing Prefrontal Activation in people with Parkinson Disease, run by Emory University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jonna Seppa (404-727-1509, jonna.k.seppa@emory.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response Time During Go/No-Go (GNG) Task for Participants in Aim 1 (time frame: Day 1 (before and after levodopa dosage for persons with PD)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2026.