Parkinson DiseaseNCT04735458
Investigating Inhibitory Control Networks in Parkinson's Disease
A study testing Procedure/Surgery: Response Inhibition and Deep Brain Stimulation in Parkinson's disease in people with Parkinson Disease, run by University of Alabama at Birmingham at 1 site in United States.
Trial summary
The purpose of this study is to investigate the brain activity associated with non-motor symptoms of movement disorders, including Parkinson's disease and essential tremor. These movement disorders commonly have significant non-motor features also, including depression, cognitive impairment, decreased attention, and… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Parkinson Disease
- What is being tested?
- Procedure/Surgery: Response Inhibition and Deep Brain Stimulation in Parkinson's disease
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Apr 2021to 31 Mar 2028
- Phase
- Interventional
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Eligible for surgery based on multi-disciplinary consensus review
- Have a diagnosis of Parkinson's disease or Essential Tremor
- Have a diagnosis of medically-refractory movement disorder (Parkinson's disease, Essential Tremor, or dystonia)
- Willingness to participate in the paradigms described in the protocol
Who cannot join
- Inability to provide full and informed consent
- Age younger than 18
- Are not able to participate in study-related activities
- History of prior ischemic/hemorrhagic stroke, subdural hemorrhage, or seizure
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Nicole Bentley, MD, 205-975-0011, jbentley@uabmc.edu
About this study
The purpose of this study is to investigate the brain activity associated with non-motor symptoms of movement disorders, including Parkinson's disease and essential tremor. These movement disorders commonly have significant non-motor features also, including depression, cognitive impairment, decreased attention, and slower processing speeds. The investigators are interested in the brain activity associated with these symptoms, and perform recordings of the surface of the brain, in addition to the typical recordings the investigators perform, during routine deep brain stimulation (DBS) surgery.
Read the detailed description
Movement disorders are a prominent cause of disability worldwide. In the United States, it is estimated that more than 4 million people suffer from Parkinson's disease (PD), essential tremor (ET), and dystonia, some of the most prevalent of neurologic disorders. Of these, PD is the most common, and is primarily characterized by tremor, rigidity, and bradykinesia. However, many patients also have prominent non-motor features, including depression and cognitive impairment, with deficiencies in processing speed, memory, attention, and learning. One of the most debilitating cognitive deficiencies is in response inhibition (RI), or the inability to suppress a habitual action. PD patients have significant difficulty with RI, and report its substantial contribution in limiting their quality of life. While some studies show that dopamine can improve this aspect of cognitive function, many patients remain considerably impaired.
RI manifests clinically in many different and important ways, with reduced mental flexibility, task-switching, and concentration. RI may also contribute to motor impairment, with gait dysfunction, falls, and freezing of gait. Unfortunately, these features of PD and RI are less well-studied and lack effective treatment options, necessitating that new treatments be investigated. Deep brain stimulation (DBS), while a highly effective treatment for motor manifestations, is essentially ineffective for, and can even worsen cognition, with few studies currently investigating how different parameters may improve NMS. In an effort to begin addressing these debilitating features of PD, the investigators propose to study RI in patients with movement disorders, and to correlate movement and cognition with underlying neural electrophysiology before and during tasks of motion and response inhibition.
During routine DBS surgery, the stimulating electrode is implanted with the aid of intraoperative recordings in the awake state. These routine recordings enable neurologists and neurosurgeons to directly observe neuronal firing in the brain, identifying characteristic patterns to delineate anatomic structures. Once in place, the DBS electrode is tested using stimulation parameters known to be clinically efficacious for motor impairment. This allows acute, intraoperative testing for therapeutic benefit and side effects, and give information for how a patient will respond to the therapy once the cranial electrode is connected to the battery and turned on.
In addition to this routine recording and stimulation, this setting also provides a unique opportunity to study neural electrophysiology, with minimal increased risk. By measuring brain activity in the outer layers (cortex) as well as from the DBS electrode itself, while patients perform various tasks, it is possible to correlate behavioral function and neural activity. Our center, and several others, already have research paradigms in place to achieve these goals, by placing a subdural strip electrode over cortex prior to placing the DBS lead. These strip electrodes lie along the surface of the brain, and have historically been used for several decades to perform seizure mapping, typically as an array of electrodes placed via a burr hole. Their use has only more recently been implemented for investigation of neural circuits during DBS surgery, however, their safety in this specific setting is now well-established, and their temporary placement is currently being performed in similar studies at this institution. However, though previous studies have placed these strips over prefrontal areas, the vast majority of research in this area is focused on motor circuits, with placement over sensorimotor cortex. In order to study NMS, strips will be placed over prefrontal cortex, with recordings made during various motor and cognitive tasks and during different stimulation patterns.
- Conditions
- Parkinson Disease
- Being tested
- Procedure/Surgery: Response Inhibition and Deep Brain Stimulation in Parkinson's disease
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Procedure/Surgery: Response Inhibition and Deep Brain Stimulation in Parkinson's diseaseOther
After creation of the burr hole and prior to DBS electrode placement, 1-2 subdural strip electrodes will be placed anteriorly or posteriorly from the cranial opening. These electrodes are routinely placed using this technique for seizure mapping, with arrays of electrodes (up to 6) being placed around the perimeter of the opening.14 Subdural strips vary in length and contact size (e.g., the 6-contact Ad-Tech strip), and are currently placed predominantly for studies of sensorimotor function,13 including at our institution (IRB-140327003). Placement over prefrontal areas is performed at other institutions.11-13 The DBS surgery will then proceed according to routine practice, and following lead placement in the optimal desired location, the research task paradigm will begin.
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Parkinson's Disease Patients receiving DBS electrodes Receives: Other: Procedure/Surgery: Response Inhibition and Deep Brain Stimulation in Parkinson's disease |
| Control | No intervention | Control subjects will be non-Parkinson's Disease patients with essential tremor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Accuracy via Simon Task (% correct)
In the Simon task, participants are instructed to respond with a right or left button press (Right = Red, Left = Blue) according to how a word is printed on a screen ("RED" or "BLUE"), regardless of the color in which the word is printed.
This is a measurement of accuracy (% correct, ranging from 0-100, with higher scores indicating better performance)
Measured: Baseline
Response times via Simon Task (sec)
In the Simon task, participants are instructed to respond with a right or left button press according to the word "RIGHT" or "LEFT" that appears on a screen, regardless of where on the screen it actually appears.
This is a measurement response times (continuous measure, from 0-4000 milliseconds) between correct and incorrect responses.
Measured: Baseline
Simon Effect on Response times (sec)
Participants will perform the Simon task as described, and the Simon effect will be calculated as the difference in response times between congruent and incongruent trials
Measured: Baseline
Simon Effect on Accuracy (% correct)
Participants will perform the Simon task as described, and the Simon effect will be calculated as the difference in accuracy between congruent and incongruent trials
Measured: Baseline
United Parkinson's disease Rating Scale part 3: Motor Examination Score 0-108 (Higher score represents worse symptoms)
Participants will undergo motor evaluation using the validated United Parkinson's disease Rating Scale (UPDRS) part 3.
Measured: Baseline
Dementia Rating Scale Score 0-144 points (Higher score represents better symptoms)
Participants will undergo neuropsychological testing as part of routine care, including the Dementia Rating Scale
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2021
- Study start1 Apr 2021
- Primary completion31 Mar 2027 (estimated)
- Study completion31 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, J. Nicole Bentley, University of Alabama at Birmingham
- Investigators
- Nicole Bentley, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04735458
- Sponsor's protocol ID
- IRB300003605
- Other IDs
- 1K23NS117735-01A1
- Status last verified
- Nov 2025
- First submitted
- 28 Jan 2021
- Last updated
- 2 Dec 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Khan AU, Irwin Z, Mahavadi A, Roller A, Goodman AM, Guthrie BL, Visscher K, Knight RT, Walker HC, Bentley JN. Low-Frequency Oscillations in Mid-rostral Dorsolateral Prefrontal Cortex Support Response Inhibition. J Neurosci. 2024 Oct 2;44(40):e0122242024. doi: 10.1523/JNEUROSCI.0122-24.2024.
PubMed 39197939
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating Inhibitory Control Networks in Parkinson's Disease
- ClinicalTrials.gov ID
- NCT04735458
- Acronym / sponsor ID
- IRB300003605
- Conditions
- Parkinson Disease
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 1 Apr 2021 (actual)
- Primary completion
- 31 Mar 2027 (estimated)
- Study completion
- 31 Mar 2028 (estimated)
- First posted
- 3 Feb 2021 (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.
The purpose of this study is to investigate the brain activity associated with non-motor symptoms of movement disorders, including Parkinson's disease and essential tremor. These movement disorders commonly have significant non-motor features also, including depression, cognitive impairment, decreased attention, and slower processing speeds. The investigators are interested in the brain activity associated with these symptoms, and perform recordings of the surface of the brain, in addition to the typical recordings the investigators perform, during routine deep brain stimulation (DBS) surgery.
Detailed description
Movement disorders are a prominent cause of disability worldwide. In the United States, it is estimated that more than 4 million people suffer from Parkinson's disease (PD), essential tremor (ET), and dystonia, some of the most prevalent of neurologic disorders. Of these, PD is the most common, and is primarily characterized by tremor, rigidity, and bradykinesia. However, many patients also have prominent non-motor features, including depression and cognitive impairment, with deficiencies in processing speed, memory, attention, and learning. One of the most debilitating cognitive deficiencies is in response inhibition (RI), or the inability to suppress a habitual action. PD patients have significant difficulty with RI, and report its substantial contribution in limiting their quality of life. While some studies show that dopamine can improve this aspect of cognitive function, many patients remain considerably impaired.
RI manifests clinically in many different and important ways, with reduced mental flexibility, task-switching, and concentration. RI may also contribute to motor impairment, with gait dysfunction, falls, and freezing of gait. Unfortunately, these features of PD and RI are less well-studied and lack effective treatment options, necessitating that new treatments be investigated. Deep brain stimulation (DBS), while a highly effective treatment for motor manifestations, is essentially ineffective for, and can even worsen cognition, with few studies currently investigating how different parameters may improve NMS. In an effort to begin addressing these debilitating features of PD, the investigators propose to study RI in patients with movement disorders, and to correlate movement and cognition with underlying neural electrophysiology before and during tasks of motion and response inhibition.
During routine DBS surgery, the stimulating electrode is implanted with the aid of intraoperative recordings in the awake state. These routine recordings enable neurologists and neurosurgeons to directly observe neuronal firing in the brain, identifying characteristic patterns to delineate anatomic structures. Once in place, the DBS electrode is tested using stimulation parameters known to be clinically efficacious for motor impairment. This allows acute, intraoperative testing for therapeutic benefit and side effects, and give information for how a patient will respond to the therapy once the cranial electrode is connected to the battery and turned on.
In addition to this routine recording and stimulation, this setting also provides a unique opportunity to study neural electrophysiology, with minimal increased risk. By measuring brain activity in the outer layers (cortex) as well as from the DBS electrode itself, while patients perform various tasks, it is possible to correlate behavioral function and neural activity. Our center, and several others, already have research paradigms in place to achieve these goals, by placing a subdural strip electrode over cortex prior to placing the DBS lead. These strip electrodes lie along the surface of the brain, and have historically been used for several decades to perform seizure mapping, typically as an array of electrodes placed via a burr hole. Their use has only more recently been implemented for investigation of neural circuits during DBS surgery, however, their safety in this specific setting is now well-established, and their temporary placement is currently being performed in similar studies at this institution. However, though previous studies have placed these strips over prefrontal areas, the vast majority of research in this area is focused on motor circuits, with placement over sensorimotor cortex. In order to study NMS, strips will be placed over prefrontal cortex, with recordings made during various motor and cognitive tasks and during different stimulation patterns.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Other: Procedure/Surgery: Response Inhibition and Deep Brain Stimulation in Parkinson's diseaseParkinson's Disease Patients receiving DBS electrodes |
| Control | No intervention | –Control subjects will be non-Parkinson's Disease patients with essential tremor |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Eligible for surgery based on multi-disciplinary consensus review
- Have a diagnosis of Parkinson's disease or Essential Tremor
- Have a diagnosis of medically-refractory movement disorder (Parkinson's disease, Essential Tremor, or dystonia)
- Willingness to participate in the paradigms described in the protocol
Key exclusion criteria (4 listed)
- Inability to provide full and informed consent
- Age younger than 18
- Are not able to participate in study-related activities
- History of prior ischemic/hemorrhagic stroke, subdural hemorrhage, or seizure
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 |
|---|---|---|
| Procedure/Surgery: Response Inhibition and Deep Brain Stimulation in Parkinson's diseaseAfter creation of the burr hole and prior to DBS electrode placement, 1-2 subdural strip electrodes will be placed anteriorly or posteriorly from the cranial opening. These electrodes are routinely placed using this technique for seizure mapping, with arrays of electrodes (up to 6) being placed around the perimeter of the opening.14 Subdural strips vary in length and contact size (e.g., the 6-contact Ad-Tech strip), and are currently placed predominantly for studies of sensorimotor function,13 including at our institution (IRB-140327003). Placement over prefrontal areas is performed at other institutions.11-13 The DBS surgery will then proceed according to routine practice, and following lead placement in the optimal desired location, the research task paradigm will begin. | Other | Treatment |
Primary outcome
Accuracy via Simon Task (% correct)
Time frame: Baseline
In the Simon task, participants are instructed to respond with a right or left button press (Right = Red, Left = Blue) according to how a word is printed on a screen ("RED" or "BLUE"), regardless of the color in which the word is printed. This is a measurement of accuracy (% correct, ranging from 0-100, with higher scores indicating better performance)
Response times via Simon Task (sec)
Time frame: Baseline
In the Simon task, participants are instructed to respond with a right or left button press according to the word "RIGHT" or "LEFT" that appears on a screen, regardless of where on the screen it actually appears. This is a measurement response times (continuous measure, from 0-4000 milliseconds) between correct and incorrect responses.
Simon Effect on Response times (sec)
Time frame: Baseline
Participants will perform the Simon task as described, and the Simon effect will be calculated as the difference in response times between congruent and incongruent trials
Simon Effect on Accuracy (% correct)
Time frame: Baseline
Participants will perform the Simon task as described, and the Simon effect will be calculated as the difference in accuracy between congruent and incongruent trials
United Parkinson's disease Rating Scale part 3: Motor Examination Score 0-108 (Higher score represents worse symptoms)
Time frame: Baseline
Participants will undergo motor evaluation using the validated United Parkinson's disease Rating Scale (UPDRS) part 3.
Dementia Rating Scale Score 0-144 points (Higher score represents better symptoms)
Time frame: Baseline
Participants will undergo neuropsychological testing as part of routine care, including the Dementia Rating Scale
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 2 Dec 2025.
- Derived from this study: PubMed 39197939Khan AU, Irwin Z, Mahavadi A, Roller A, Goodman AM, Guthrie BL, Visscher K, Knight RT, Walker HC, Bentley JN. Low-Frequency Oscillations in Mid-rostral Dorsolateral Prefrontal Cortex Support Response Inhibition. J Neurosci. 2024 Oct 2;44(40):e0122242024. doi: 10.1523/JNEUROSCI.0122-24.2024.
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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.
Nicole Bentley, MD principal investigator
University of Alabama at Birmingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Procedure/Surgery: Response Inhibition and Deep Brain Stimulation in Parkinson's disease in people with Parkinson Disease, run by University of Alabama at Birmingham at 1 site 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 4 inclusion and 4 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 2 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
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 Nicole Bentley, MD (205-975-0011, jbentley@uabmc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Accuracy via Simon Task (% correct) (time frame: Baseline). 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?
On the ClinicalTrials.gov record for NCT04735458, which also lists 1 linked publication.
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 2 Dec 2025.