Neural correlates of post-traumatic brain injury (TBI) attention deficits in children

Traumatic brain injury (TBI) in children is a major public health concern worldwide. Attention deficits are among the most common neurocognitive and behavioral consequences in children post-TBI which have significant negative impacts on their educational and social outcomes and compromise the quality of their lives. However, there is a paucity of evidence to guide the optimal treatment strategies of attention deficit related symptoms in children post-TBI due to the lack of understanding regarding its neurobiological substrate. Thus, it is critical to understand the neural mechanisms associated with TBI-induced attention deficits in children so that more refined and tailored strategies can be developed for diagnoses and long-term treatments and interventions. This dissertation is the first study to investigate neurobiological substrates associated with post-TBI attention deficits in children using both anatomical and functional neuroimaging data. The goals of this project are to discover the quantitatively measurable markers utilizing diffusion tensor imaging (DTI), structural magnetic resonance imaging (MRI), and functional MRI (fMRI) techniques, and to further identify the most robust neuroimaging features in predicting severe post-TBI attention deficits in children, by utilizing machine learning and deep learning techniques. A total of 53 children with TBI and 55 controls from age 9 to 17 are recruited. The results show that the systems-level topological properties in left frontal regions, parietal regions, and medial occipitotemporal regions in structural and functional brain network are significantly associated with inattentive and/or hyperactive/impulsive symptoms in children post-TBI. Semi-supervised deep learning modeling further confirms the significant contributions of these brain features in the prediction of elevated attention deficits in children post-TBI. The findings of this project provide valuable foundations for future research on developing neural markers for TBI-induced attention deficits in children, which may significantly assist the development of more effective and individualized diagnostic and treatment strategies

Exploring memory impairment and post-traumatic amnesia following traumatic brain injury

Memory disturbances are among the most common and significant consequences of traumatic brain injury (TBI). The severity of these deficits can vary widely across the trajectory of recovery from TBI and can be highly heterogenous across individuals. In the acute stages memory disturbance can occur in the form of post-traumatic amnesia (PTA), but deficits are also present into the chronic stages of recovery. I present four studies that aim to understand the characteristics and underlying mechanisms of memory impairment following TBI. I investigated the cognitive profile of acute TBI patients with and without PTA. I found PTA patients show a transient deficit in working memory binding. I then assessed electrophysiological abnormalities to test the hypothesis that the binding deficit is underpinned by pathological low frequency slow-wave activity. PTA patients showed a significantly higher delta to alpha power ratio that correlated with binding impairment. To understand how this disruption to cortical communication impacts upon large-scale networks I performed a dynamic functional connectivity analysis on the resting state fMRI of acute TBI patients. I found four independent brain states that showed striking anti-correlation between core cognitive control networks. Patients in a more profound period of PTA spent more time in fewer states than those with less cognitive impairment. These findings suggest that PTA is likely underpinned by disruption to communication required for integration of features in working memory. Finally, I examined enduring memory failures in chronic TBI patients and found that patients with episodic memory impairment showed differential activation of key networks required for memory and attention. Memory impairment related to the white matter integrity directly underpinning the task-derived encoding networks. These findings suggest that in chronic TBI memory impairment may be associated with failed control of attentional resources.Open Acces