Neural Dynamics and Connectivity in Response Inhibition and Traumatic Brain Injury

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.