The Neurocognitive Sequelae of Chronic Traumatic Brain Injury and the Utility of Treatment with Methylphenidate

Traumatic Brain Injury (TBI) is a serious world-wide public health concern with a pressing need for adequate, effective long-term treatment. Cognitive deficits are a common complaint after TBI and persistent disabilities endure well into the chronic phases of the injury. Few recognised standard treatments exist for treating cognitive deficits associated with TBI. Advances in Magnetic Resonance Imaging (MRI) technology using structural, functional, and diffusion imaging have shown utility in revealing subtle neurobiological abnormalities in patients with TBI which were previously undetectable with routine brain imaging. These have been employed here to study the behavioural, cognitive, and functional consequences of TBI alongside the neurobiological correlates of improved cognition with pharmacological treatment i.e., Methylphenidate (MPh). This work aims to further our understanding of the detrimental functional consequences of TBI and inform targeted neurorehabilitation options. In the first experimental chapter, I use task-based functional MRI data acquired during a Tower of London (TOL) task that gauges working memory, visuospatial planning, and executive function i.e., executive planning. I explore the detrimental effects of TBI and the usefulness of MPh treatment on behavioural performance, activity, regional connectivity, and MPh-driven behavioural-neurofunctional relationships. I found that patients with TBI have deficits in accuracy and reaction time, together with differences in activity and connectivity, and some of these deficits are ameliorated with a single dose of MPh. These were in the insula, striatum, thalamus, parietal, and cerebellar regions. Moreover, differences in connectivity between the cerebellum, thalamus, and parietal cortex indicate MPh-driven behavioural improvements. In the second experimental chapter, I use task-based functional MRI data collected during a Rapid Visual Information Processing (RVIP) task that evaluates attention, and more specifically, one particular domain, namely ...