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