Neural Dynamics and Connectivity in Response Inhibition and Traumatic Brain Injury
Neural Dynamics and Connectivity in Response Inhibition and Traumatic Brain Injury
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.
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.
-  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 such as
 those for seizures (e.g., carbamazepine, phenytoin) except for short-lasting
 benzodiazepines for sleep and antidepressants (e.g., SSRIs and SNRIs).

 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 severe post traumatic stress disorder (PTSD)
 or PTSD Check List (PCL) score > 60

 7. Penetrating head wound

 8. For healthy volunteer, history of brain injury and/or structural MRI abnormality.

 9. Staff from our section