Neural Dynamics and Connectivity in Response Inhibition and Traumatic Brain Injury

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Collaborators:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01194661
First received: September 2, 2010
Last updated: May 21, 2014
Last verified: March 2014
  Purpose

Background:

- Previous research has shown that certain parts of the brain are involved in voluntarily stopping an ongoing motor response (movement); however, it is not known whether this same network is also involved in suppressing an urge to act. Traumatic brain injury (TBI) can significantly impair the brain's ability to voluntarily stop or inhibit certain actions. Using brain imaging (functional magnetic resonance imaging, or fMRI) and brain stimulation (transcranial magnetic stimulation, or TMS) to investigate how people perform activities that involve moving and suppressing movements, researchers hope to better understand how these brain areas might be affected in people who have had TBI.

Objectives:

  • To determine the parts of the brain involved in suppressing an urge to act.
  • To determine the extent to which traumatic brain injury affecting certain parts of the brain is involved in problems with suppressing an urge to move and stopping movement.

Eligibility:

- Individuals 18 to 40 years of age who have had mild or moderate TBI, or are healthy volunteers.

Design:

  • This research study includes a screening visit and two study visits, each of which will last at least 2 hours.
  • Participants will be screened with a physical examination and medical history. Women who can become pregnant will have a urine pregnancy test before being allowed to participate in the study.
  • At the first study visit, participants will complete one of the following experiment tests in an MRI scanner.
  • Experiment 1: Participants will be shown arrows or images on a computer screen, and will press a button or not press a button depending on the image shown. Participants will practice the experiment tasks before performing them during MRI scans.
  • Experiment 2: Participants will be shown arrows or images on a computer screen, and will press a button or not press a button depending on the image shown. Participants will also have TMS while at rest, and will perform the experiment tasks during the MRI scan.
  • At the second study visit, participants will have an fMRI scan where they will be asked to do simple response tasks with a computer outside the MRI scanner.

Background:

- Previous research has shown that certain parts of the brain are involved in voluntarily stopping an ongoing motor response (movement); however, it is not known whether this same network is also involved in suppressing an urge to act. Traumatic brain injury (TBI) can significantly impair the brain's ability to voluntarily stop or inhibit certain actions. Using brain imaging (functional magnetic resonance imaging, or fMRI) and brain stimulation (transcranial magnetic stimulation, or TMS) to investigate how people perform activities that involve moving and suppressing movements, researchers hope to better understand how these brain areas might be affected in people who have had TBI.

Objectives:

  • To determine the parts of the brain involved in suppressing an urge to act.
  • To determine the extent to which traumatic brain injury affecting certain parts of the brain is involved in problems with suppressing an urge to move and stopping movement.

Eligibility:

- Individuals 18 to 40 years of age who have had mild or moderate TBI, or are healthy volunteers.

Design:

  • This research study includes a screening visit and two study visits, each of which will last at least 2 hours.
  • Participants will be screened with a physical examination and medical history. Women who can become pregnant will have a urine pregnancy test before being allowed to participate in the study.
  • At the first study visit, participants will complete one of the following experiment tests in an MRI scanner.
  • Experiment 1: Participants will be shown arrows or images on a computer screen, and will press a button or not press a button depending on the image shown. Participants will practice the experiment tasks before performing them during MRI scans.
  • Experiment 2: Participants will be shown arrows or images on a computer screen, and will press a button or not press a button depending on the image shown. Participants will also have TMS while at rest, and will perform the experiment tasks during the MRI scan.
  • At the second study visit, participants will have an fMRI scan where they will be asked to do simple response tasks with a computer outside the MRI scanner.

Condition
Traumatic Brain Injury
Stroke
Headache
PTSD

Study Type: Observational
Official Title: Neural Dynamics and Connectivity in Response Inhibition and Traumatic Brain Injury

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • 2) TMS effects on behavioral performance
  • Task-dependent and independent fMRI BOLD signal
  • Task - dependent and independent fMRI BOLD signal
  • TMS effects on behavioral performance

Secondary Outcome Measures:
  • Behavioral performance data (reaction time and accuracy)
  • White matter fiber integrity in TBI patients estimated by the degree of fractional anisotropy (FA) from diffusion tensor imaging (DTI) signals.

Estimated Enrollment: 285
Study Start Date: August 2010
Detailed Description:

Objectives

Voluntarily stopping an on-going motor response has been shown to engage a specific prefrontal-basal-ganglia (PBG) neural network. However, it is not known whether the PBG network is also crucial for other types of response inhibition such as suppressing an urge to act (i.e., habitual impulse), a common impairment after traumatic brain injury (TBI). The objectives of this protocol are: 1) to determine whether the PBG network is engaged in suppressing habitual impulses and, 2) to determine the extent to which the (PBG) neural network can account for the deficiency in response inhibition after mild to moderate traumatic brain injury (TBI). The proposed studies will involve performance of simple behavioral tasks, functional magnetic resonance imaging (fMRI), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and diffusion tensor imaging (DTI). tDCS will be applied separately from fMRI scans. TMS will be applied separately or concurrently during fMRI scans.

Study Population

One hundred and ninety healthy adult volunteers and 95 patients with mild to moderate TBI will be recruited under the protocol. Eighty of the healthy volunteers and 80 of the patients will be recruited under the project funded by the Center for Neuroscience and Rehabilitative Medicine (CNRM) at the Uniformed Services University of the Health Sciences (USUHS).

Design

There are five experiments. Experiment 1 includes healthy adult volunteers and mild to moderate TBI patients to determine whether the PBG inhibitory network is engaged in the suppression of an undesirable habitual impulse. Subjects will perform simple motor response tasks during fMRI scans. Experiment 2 will use fMRI with behavioral tasks and apply single-pulse TMS during fMRI scans when subjects are at rest to examine whether changes in the active and resting neural connectivity within the PBG network are associated with deficiency in response inhibition after mild to moderate TBI. Experiment 3 will involve only healthy volunteers to determine the effect of disruption of critical links/brain regions within the PBG network on response inhibition. Inhibitory rTMS (i.e., 1Hz repetitive TMS with stimulation intensity at 80% of a subject s own resting motor threshold [rMT]) will be applied in separate groups of subjects immediately before the behavioral tasks. Experiments 4-5 will use similar response tasks as in Experiment 1 but with patients who have had blast induced concussion(s). tDCS will be applied in Experiment 5 to examine the extent to which tDCS may change connectivity and improve rapid response inhibition. Additional behavioral measures, DTI, and high-resolution structural MRI images will be acquired in a separate session for all subjects.

Outcome Measures

Major outcome measures will include: 1) Task and TMS induced fMRI BOLD signal change and, 2) Behavioral performance data (reaction time and accuracy). Secondary measures: White matter fiber integrity and fiber tracking based on diffusion tensor imaging data.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

    1. Age 18 to 40
    2. Able to give consent
    3. Normal clinical examination for healthy subjects
    4. Must be able to follow instructions and perform required tasks, and TBI patients must have the Mini-mental state examination (MMSE) score of 25 or above.
    5. Clearly right dominant handedness as assessed by Handedness scales

MILD TBI:

Traumatically induced physiological disruption of brain function, as manifested by at least on the following:

  1. Any loss of consciousness
  2. Any loss of memory for events immediately before or after the accident (except for short-lasting benzodiazepines for sleep.
  3. Focal neurological deficit(s) that may or may not be transient
  4. Any alteration in metal state at the time of the accident (e.g. feeling dazed, disoriented or confused) and focal neurological deficit (s) that may or may not be transient, but where the severity of the injury does not exceed the following:

    • Loss of consciousness (LOC) of approximately 30 min
    • After 30 min, an initial Glasgow Coma Scale (GCS) sore of 13 - 15 (or clinically diagnosed concussion) and
    • Post-traumatic amnesia (PTA) not greater than 24 hour

Moderate TBI:

Those meeting the same criteria as mild TBI plus any one of the following:

  1. GCS of 9-12 (if available) or results of a clinical evaluation as moderate TBI
  2. Mental status change or LOC 30 min to 24 hour
  3. PTA 1-7 days

EXCLUSION CRITERIA:

  1. Being diagnosed as an alcoholic or with drug addiction.
  2. Chronic use of medications acting primarily on the central nervous system (e.g., carbamazepine, phenytoin, citalopram, and fluoxetine) except for short-lasting benzodiazepines for sleep
  3. Pregnancy
  4. Medical or technical contraindications to MRI procedures or devices producing artifacts that impair MRI signal (e.g., dental braces, pacemakers, implanted medication pumps, cochlear devices, neural stimulators, certain metals in the cranium, surgical clips, and other metal/magnetic implants, claustrophobia)
  5. History of epilepsy (to avoid brain abnormalities other than mild to moderate TBI)
  6. Less than three months post-TBI and with post traumatic stress disorder (PTSD) Check List (PCL) score of greater than or equal to 50
  7. Penetrating head wound
  8. For healthy volunteer, history of brain injury and/or structural MRI abnormality.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01194661

Contacts
Contact: Rita Volochayev, C.R.N.P. (301) 402-0546 volochar@mail.nih.gov
Contact: Leonardo G Cohen, M.D. (301) 496-9782 cohenl1@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Leonardo G Cohen, M.D. National Institute of Neurological Disorders and Stroke (NINDS)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT01194661     History of Changes
Other Study ID Numbers: 100185, 10-N-0185
Study First Received: September 2, 2010
Last Updated: May 21, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Inhibitory Control
Executive Function
fMRI
TMS
TBI
Traumatic Brain Injury
Healthy Volunteer
HV

Additional relevant MeSH terms:
Headache
Stroke
Brain Injuries
Wounds and Injuries
Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Craniocerebral Trauma
Trauma, Nervous System

ClinicalTrials.gov processed this record on July 20, 2014