Sensory Filtering in the Human Basal Ganglia as a Mechanism of Parkinson's Disease

• ClinicalTrials.gov Identifier: NCT05482126
• Recruitment Status: Recruiting
• First Posted: August 1, 2022
• Last Update Posted: April 25, 2024
• Sponsor: University of Alabama at Birmingham
• Collaborator: National Institute of Neurological Disorders and Stroke (NINDS)
• Information provided by (Responsible Party): Zachary Irwin, University of Alabama at Birmingham

Tracking Information

• First Submitted Date: July 26, 2022
• First Posted Date: August 1, 2022
• Last Update Posted Date: April 25, 2024
• Actual Study Start Date: June 8, 2022
• Estimated Primary Completion Date: January 1, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 1, 2022)

• Kinematic response to stimulus (intraoperative) [ Time Frame: Intraoperative ]
  Arm movements (hand position, velocity) recorded following stimulus onset, measured by joystick outputs.
• Kinematic response to stimulus (postoperative) [ Time Frame: 1 month post-op ]
  Arm movements (hand position, velocity) recorded following stimulus onset, measured by joystick outputs.
• Latency of response to stimulus (intraoperative) [ Time Frame: Intraoperative ]
  Time from stimulus onset to start of motor response, measured by electromyography (EMG)
• Latency of response to stimulus (postoperative) [ Time Frame: 1 month post-op ]
  Time from stimulus onset to start of motor response, measured by electromyography (EMG)
• Neural response to stimulus [ Time Frame: Intraoperative ]
  Brain activity recorded following stimulus onset, measured by local field potentials recorded from the electrocorticography (ECoG) and DBS electrodes.

Original Primary Outcome Measures (submitted: July 27, 2022)

• Kinematics [ Time Frame: Intraoperative ]
  Joint position and joint angles (degrees, radians), grip force, tremor/movement amplitudes (mVolts) and frequencies (Hz) from EMG, motion capture, dynamometer, joystick, and accelerometry may be captured during each of the intraoperative stimulation conditions.
• Task Performance - Accuracy [ Time Frame: Intraoperative ]
  Tasks will be administered via a tablet PC or mounted monitor, and the subject may hold a response box, joystick, or dynamometer to record responses. During task periods, sensory stimuli will be delivered to the participant, who may be asked to perform a motor behavior in response. Stimuli will consist of audiovisual cues presented on a computer screen, vibration applied to specific parts of the body via a tactor attached with a Velcro strap, or mild electrical pulses delivered through the skin of specific parts of the body via the attached EMG electrodes. Motor responses will consist of simple movements such as finger-tapping or hand-opening, or use of a joystick or dynamometer to move a computer cursor on the screen. Participants may be asked to respond only to a particular sensory stimulus and ignore others. Sensory stimuli and motor behaviors may be delivered or performed without the other.
• Task Performance - Reaction Times (msec) [ Time Frame: Intraoperative ]
  Tasks will be administered via a tablet PC or mounted monitor, and the subject may hold a response box, joystick, or dynamometer to record responses. During task periods, sensory stimuli will be delivered to the participant, who may be asked to perform a motor behavior in response. Stimuli will consist of audiovisual cues presented on a computer screen, vibration applied to specific parts of the body via a tactor attached with a Velcro strap, or mild electrical pulses delivered through the skin of specific parts of the body via the attached EMG electrodes. Motor responses will consist of simple movements such as finger-tapping or hand-opening, or use of a joystick or dynamometer to move a computer cursor on the screen. Participants may be asked to respond only to a particular sensory stimulus and ignore others. Sensory stimuli and motor behaviors may be delivered or performed without the other.
• Task Performance - Accuracy-Response Time Plots [ Time Frame: Intraoperative ]
  Tasks will be administered via a tablet PC or mounted monitor, and the subject may hold a response box, joystick, or dynamometer to record responses. During task periods, sensory stimuli will be delivered to the participant, who may be asked to perform a motor behavior in response. Stimuli will consist of audiovisual cues presented on a computer screen, vibration applied to specific parts of the body via a tactor attached with a Velcro strap, or mild electrical pulses delivered through the skin of specific parts of the body via the attached EMG electrodes. Motor responses will consist of simple movements such as finger-tapping or hand-opening, or use of a joystick or dynamometer to move a computer cursor on the screen. Participants may be asked to respond only to a particular sensory stimulus and ignore others. Sensory stimuli and motor behaviors may be delivered or performed without the other.
• Task Performance - Accuracy - Month 1 [ Time Frame: 1 month postop ]
  Tasks will be administered via a tablet PC or mounted monitor, and the subject may hold a response box, joystick, or dynamometer to record responses. During task periods, sensory stimuli will be delivered to the participant, who may be asked to perform a motor behavior in response. Stimuli will consist of audiovisual cues presented on a computer screen, vibration applied to specific parts of the body via a tactor attached with a Velcro strap, or mild electrical pulses delivered through the skin of specific parts of the body via the attached EMG electrodes. Motor responses will consist of simple movements such as finger-tapping or hand-opening, or use of a joystick or dynamometer to move a computer cursor on the screen. Participants may be asked to respond only to a particular sensory stimulus and ignore others. Sensory stimuli and motor behaviors may be delivered or performed without the other.
• Task Performance - Reaction Times (msec) - Month 1 [ Time Frame: 1 month postop ]
  Tasks will be administered via a tablet PC or mounted monitor, and the subject may hold a response box, joystick, or dynamometer to record responses. During task periods, sensory stimuli will be delivered to the participant, who may be asked to perform a motor behavior in response. Stimuli will consist of audiovisual cues presented on a computer screen, vibration applied to specific parts of the body via a tactor attached with a Velcro strap, or mild electrical pulses delivered through the skin of specific parts of the body via the attached EMG electrodes. Motor responses will consist of simple movements such as finger-tapping or hand-opening, or use of a joystick or dynamometer to move a computer cursor on the screen. Participants may be asked to respond only to a particular sensory stimulus and ignore others. Sensory stimuli and motor behaviors may be delivered or performed without the other.
• Task Performance - Accuracy-Response Time Plots - Month 1 [ Time Frame: 1 month postop ]
  Tasks will be administered via a tablet PC or mounted monitor, and the subject may hold a response box, joystick, or dynamometer to record responses. During task periods, sensory stimuli will be delivered to the participant, who may be asked to perform a motor behavior in response. Stimuli will consist of audiovisual cues presented on a computer screen, vibration applied to specific parts of the body via a tactor attached with a Velcro strap, or mild electrical pulses delivered through the skin of specific parts of the body via the attached EMG electrodes. Motor responses will consist of simple movements such as finger-tapping or hand-opening, or use of a joystick or dynamometer to move a computer cursor on the screen. Participants may be asked to respond only to a particular sensory stimulus and ignore others. Sensory stimuli and motor behaviors may be delivered or performed without the other.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Sensory Filtering in the Human Basal Ganglia as a Mechanism of Parkinson's Disease
• Official Title: Sensory Filtering in the Human Basal Ganglia as a Mechanism of Parkinson's Disease
• Brief Summary: The investigators are investigating the brain activity associated with sensory information in movement disorders in order to improve treatment of these symptoms beyond what is currently available.

Detailed Description

The purpose of this study is to investigate the functional role of the human basal ganglia in the sensorimotor system. In particular, the investigators are interested in the possibility that the basal ganglia participate in "filtering out" sensory stimuli that are irrelevant to the current behavioral goal. Additionally, the investigators are interested in how this type of sensorimotor processing in these brain areas is related to the severity of movement disorders such as Parkinson's disease and essential tremor.

To do this, the investigators will study both healthy individuals and Parkinson's disease patients undergoing routine deep brain stimulation (DBS) surgery. During the surgery, investigators will place the DBS electrode as routinely performed and additionally place an extra, temporary "strip" electrode along the surface of the brain. Participants will then perform a short behavioral task testing sensorimotor function while investigators record the neural signals from these electrodes. The task will involve the delivery of sensory stimuli (visual, vibrotactile, electrical, and/or proprioceptive), to which the participant will be asked to perform a certain motor response. In order to fully measure the variables of interest, investigators will also attach small stickers (electrodes) to the skin of areas involved in movements for measuring muscle activity (such as the face and limbs), and may attach small, noninvasive devices around the wrist, finger, or arm (e.g., accelerometers) that measure position. The investigators may also apply EEG electrodes to the scalp to measure global brain activity or place a microphone in front of the subject to record speech.

In addition to recording this baseline brain activity, the investigators will evaluate whether deep brain stimulation and dopaminergic medication alters the recorded activity and task performance. Typical deep brain stimulation involves administering specific parameters of high-frequency electrical pulses to achieve clinical benefit. Routine operations involve testing these parameters in the OR in awake patients. For this study, investigators will administer either this high-frequency stimulation or various other patterns of stimulation (e.g., low-frequency, burst stimulation) and measure the changes in behavior and brain activity. As a method of validation, the investigators will also deliver paired pulses of stimulation that enable analysis of stimulation-evoked activity.

Finally, the investigators will correlate recorded brain activity with measures of participants' individual disease severity.

• Study Type: Observational
• Study Design: Observational Model: Case-Control; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Patients with Parkinson's disease (PD) who have been approved for deep brain stimulation surgery (DBS) as part of their routine clinical care, as well as healthy controls with no known movement disorder diagnoses
• Condition: Parkinson Disease

Intervention

• Diagnostic Test: Intraoperative Behavioral Testing
  During DBS surgery, tasks will be administered via a tablet PC or mounted monitor, and the subject may hold a response box, joystick, or dynamometer to record responses. During task periods, sensory stimuli will be delivered to the participant, who may be asked to perform a motor behavior in response. Stimuli will consist of audiovisual cues presented on a computer screen, vibration applied to specific parts of the body via a tactor, mild electrical pulses delivered through the skin of specific parts of the body via the attached EMG electrodes, and/or a movement of the arm or joint. Motor responses will consist of simple movements such as finger-tapping or hand-opening, or use of a joystick or dynamometer to move a computer cursor on the screen. Participants may be asked to respond only to a particular sensory stimulus and ignore others, in order to modulate the relevance of each stimulus to the task.
• Diagnostic Test: Behavioral Testing
  In the lab, tasks will be administered via a tablet PC or mounted monitor, and the subject may hold a response box, joystick, or dynamometer to record responses. During task periods, sensory stimuli will be delivered to the participant, who may be asked to perform a motor behavior in response. Stimuli will consist of audiovisual cues presented on a computer screen, vibration applied to specific parts of the body via a tactor, mild electrical pulses delivered through the skin of specific parts of the body via the attached EMG electrodes, and/or a movement of the arm or joint. Motor responses will consist of simple movements such as finger-tapping or hand-opening, or use of a joystick or dynamometer to move a computer cursor on the screen. Participants may be asked to respond only to a particular sensory stimulus and ignore others, in order to modulate the relevance of each stimulus to the task.

Study Groups/Cohorts

• Deep Brain Stimulation Surgery Patients
  The investigators will seek to enroll people with Parkinson's disease (PD) who have been approved for deep brain stimulation surgery (DBS) as part of their routine clinical
  Interventions:

  • Diagnostic Test: Intraoperative Behavioral Testing
  • Diagnostic Test: Behavioral Testing
• Healthy controls
  The investigators will seek to enroll a cohort of age- and sex-matched healthy individuals to act as a control group. This group will NOT undergo DBS surgery
  Intervention: Diagnostic Test: Behavioral Testing

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 27, 2022): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 30, 2026
• Estimated Primary Completion Date: January 1, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria (PD participants):

1. Age >18 years
2. Clinically definite, advanced idiopathic PD based on consensus criteria.
3. Normal, or essentially normal, preoperative brain MRI.
4. Patient is available for follow-up visits over the length of the study
5. Patient has elected to undergo DBS surgery as part of routine care, and subthalamic nucleus (STN) is determined as the appropriate surgical target

Inclusion criteria (control participants):

1. Age >18 years.
2. No diagnosis of PD, other movement disorder, or other significant neurological disease.

Exclusion criteria (PD participants):

1. Age <18 years.
2. Medical contraindications such as current uncontrolled hypertension, heart disease, coagulopathy, or other conditions that might increase the risk of surgery
3. Diagnosis or suspicion of atypical Parkinsonism (PSP, MSA, CBD) or drug-induced Parkinsonism, or significant neurological disease other than PD.
4. Diagnosis of psychogenic movement disorder based on consensus criteria
5. Prior DBS surgery or ablation
6. Clinical dementia and/or Dementia Rating Scale (DRS) score of <5th percentile adjusted for age and education level, based upon routine pre-op NP testing.
7. Unable to withhold dopaminergic medications for at least 12 hours prior to scheduled visit

Exclusion criteria (control participants):

1. Age <18 years.
2. Previous diagnosis of PD, other movement disorder, or other significant neurological disease.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 89 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Zachary Irwin, PhD; (205) 934-6704; zirwin@uabmc.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05482126
• Other Study ID Numbers: IRB-300008936; R01NS124563 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Zachary Irwin, University of Alabama at Birmingham
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Alabama at Birmingham
• Original Study Sponsor: Same as current
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

• Principal Investigator: Zachary Irwin, PhD; The University of Alabama at Birmingham

• PRS Account: University of Alabama at Birmingham
• Verification Date: April 2024