Neural Dynamics and Connectivity in Response Inhibition and Traumatic Brain Injury
Condition: Traumatic Brain Injury; Stroke; Headache; PTSD
MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Headache; Wounds and Injuries
Study type: Observational

Summary: 
      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.
    

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.
    

Observational model: Cohort
Time perspective: Other
Keywords: Inhibitory Control; Executive Function; fMRI; TMS; TBI; Traumatic Brain Injury; Healthy Volunteer; HV