| Traumatic brain injury (TBI) is the most common cause of disability among young adults, and a single traumatic event may have lifelong implications. This dissertation begins by providing a background on the current understanding of the systemic and cellular level understanding of the TBI disease state. Next, three scientific studies are presented. Each assesses a different aspect of longitudinal TBI-induced brain change by following a cohort of TBI patients for a four year period post-injury. The first study uses diffusion tensor imaging to assess how white matter damage progresses, and whether white matter change has neuropsychological correlates. Results indicate that while some brain regions, such as the corpus callosum, show continued longitudinal degeneration for several years following an injury, other regions exhibit longitudinal improvements. Specifically, bilateral regions of the superior longitudinal fasiculus demonstrate significant increases in white matter integrity in patients, something never previously observed in human patients. The second study uses tensor based morphometry to identify regional patterns of volumetric contraction following TBI. Results indicate that TBI patients exhibit volume loss throughout the brain (both in gray and white matter) during the first year post-injury, and pervasive continued volume loss focused in brain white matter between the second and fourth years post-injury. The final study uses functional MRI to observe patient BOLD response to a memory encoding task. Results indicate that patient exhibit much greater variability in their patterns of activation than controls. Furthermore, patients with low levels of cognitive reserve tend to hypo-activate, while patients with more severe injuries tend to hyper-activate to the task. Four years post injury, all patients ages 28 and under demonstrated normalized patterns of activation while none of the patients ages 29 and over exhibited normalized BOLD responses. Taken together, these studies indicate that TBI should be treated not as an isolated incident, but as the initiation of a disease state. The final chapter discusses how these three studies relate to one another, what their clinical implications may be, and what future directions may be best for continued study of the TBI disease state. |
