abstract: Development of post-traumatic epilepsy (PTE) after traumatic brain injury (TBI) is a major health concern (5% - 50% of TBI cases). A significant problem in TBI management is the inability to predict which patients will develop PTE. Such prediction, followed by timely treatment, could be highly beneficial to TBI patients. Six male Sprague-Dawley rats were subjected to a controlled cortical impact (CCI). A 6mm piston was pneumatically driven 3mm into the right parietal cortex with velocity of 5.5m/s. The rats were subsequently implanted with 6 intracranial electroencephalographic (EEG) electrodes. Long-term (14-week) continuous EEG recordings were conducted. Using linear (coherence) and non-linear (Lyapunov exponents) measures of EEG dynamics in conjunction with measures of network connectivity, we studied the evolution over time of the functional connectivity between brain sites in order to identify early precursors of development of epilepsy. Four of the six TBI rats developed PTE 6 to 10 weeks after the initial insult to the brain. Analysis of the continuous EEG from these rats showed a gradual increase of the connectivity between critical brain sites in terms of their EEG dynamics, starting at least 2 weeks prior to their first spontaneous seizure. In contrast, for the rats that did not develop epilepsy, connectivity levels did not change, or decreased during the whole course of the experiment across pairs of brain sites. Consistent behavior of functional connectivity changes between brain sites and the "focus" (site of impact) over time was demonstrated for coherence in three out of the four epileptic and in both non-epileptic rats, while for STLmax in all four epileptic and in both non-epileptic rats. This study provided us with the opportunity to quantitatively investigate several aspects of epileptogenesis following traumatic brain injury. Our results strongly support a network pathology that worsens with time. It is conceivable that the observed changes in spatiotemporal dynamics after an initial brain insult, and long before the development of epilepsy, could constitute a basis for predictors of epileptogenesis in TBI patients. / Dissertation/Thesis / M.S. Bioengineering 2012

Intracranial monitoring after severe traumatic brain injury offers the possibility for early detection and amelioration of physiological insults. In this thesis, I explore cerebral insults due raised intracranial pressure, decreased cerebral perfusion pressure and impaired cerebral pressure reactivity after traumatic brain injury. In chapter 2, the importance of intracranial pressure, cerebral perfusion pressure and pressure reactivity in regulating the cerebral circulation is elucidated along with a summary of the existing evidence supporting intracranial monitoring in traumatic brain injury. In chapter 4, intracranial pressure, cerebral perfusion pressure, and pressure reactivity insults are demonstrated to be common, prognostically important, and responsive to long-term changes in management policies. Further, while these insults often occur independently, coexisting insults portend worse prognosis. In chapter 5, I examine possible imaging antecedents of raised intracranial pressure and demonstrate that initial subarachnoid haemorrhage is associated with the subsequent development of elevated intracranial pressure. In addition, elevated glucose during the intensive care stay is associated with worse pressure reactivity. Cortical blood flow and brain tissue oxygenation are demonstrated to be sensitive to increases in intracranial pressure in chapter 6. In chapter 7, a method is proposed to estimate the cerebral perfusion pressure limits of reactivity in real-time, which may allow for more nuanced intensive care treatment. Finally, I explore a recently developed visualisation technique for intracranial physiological insults and apply it to the cerebral perfusion pressure limits of reactivity. Taken together, this thesis outlines the scope, risk factors and consequences of intracranial insults after severe traumatic brain injury. Novel signal processing applications are presented that may serve to facilitate a physiological, personalised and precision approach to patient therapy.

Objective: Research has demonstrated deficits in socio-emotional processing following childhood traumatic brain injury (TBI; Tonks et al., 2009a). However, it is not known whether a link exists between socio-emotional processing, TBI and offending. Drawing on Ochsner’s (2008) socio-emotional processing model, the current study aimed to investigate facial emotion recognition accuracy and bias in young offenders with TBI. Setting: Research was conducted across three youth offender services. Participants: Thirty seven participants completed the study. Thirteen participants reported a high dosage of TBI. Design: The study had a cross sectional within and between subjects design. Main Measures: Penton-Voak and Munafo’s (2012) emotional recognition task was completed. Results: The results indicated that young offenders with a TBI were not significantly worse at facial emotion recognition compared to those with no TBI. Both groups showed a bias towards positive emotions. No between group differences were found for emotion bias. Conclusion: The findings did not support the use of Ochsner’s (2008) socio-emotional processing model for this population. Due to the small sample size, inadequate power and lack of non-offender control groups, it is not possible to draw any firm conclusions from the results of this study. Future research should aim to investigate whether there are any links between TBI, socio-emotional processing and offending.

xiii, 79 p. : ill. A print copy of this thesis is available through the UO Libraries. Search the library catalog for the location and call number. / Traumatic brain injury has reached epidemic levels, and yet there are still large questions that need to be addressed regarding the underlying pathology and the related behavioral deficits. Adequately measuring the neurological sequelae associated with TBI in vivo requires the use of sophisticated imaging procedures, while quantifying behavioral deficits requires precise, sensitive testing procedures. The current analysis examined three potential biomarkers of TBI using MRI technology, as well as examining both fine motor and psychological function on a cohort of TBI participants at least 12 months post-injury. Ten participants with a history of traumatic brain injury and ten matched controls were recruited for the present analysis. All participants completed a series of four MRI scans, as well as a simple motor task and a cognitive test battery. Between group analysis revealed that the two groups could be differentiated based on two MRI measures (BOLD and FA), and on three behavioral measures (Fitts motor task, self-reported symptoms, and impulse control). A within group correlation analysis of the TBI participants did not reveal any significant relationship between the MRI data and behavioral deficits. A group-wide regression analysis, however, revealed that MRI markers of cortical damage significantly predicted deterioration in the Fitts motor task performance. The results of the current study suggest that the long-term effects of TBI are not confined to executive function, and that one's performance of a fine motor task has diagnostic potential. / Adviser: Paul van Donkelaar

xii, 98 p. : ill. (some col.) / The short and long term pathophysiology of traumatic brain injury (TBI) has not been fully elucidated. Individuals recently suffering a mild TBI (mTBI) or having a history of TBI frequently suffer deficits in their ability to maintain and allocate attention within and between tasks. This dissertation examines the influence of mild and chronic TBI on performance of task switching. We employed spatial and numerical task switching paradigms to assess the behavioral deficits in mTBI, and we used an internally generated switching and an externally cued switching task along with functional Magnetic Resonance Imaging (fMRI) to assess the long term deficits in executive function resulting from chronic TBI. In the first experiment, individuals with mTBI were identified and tested within the first 48 hours of injury and then at a set interval 5, 14, and 28 days post injury. In the second investigation, individuals with chronic TBI were tested at least 12 months after their most recent injury. Healthy gender, age, and education matched controls were also tested in both studies. This research demonstrated that mTBI subjects display deficits in switching behavior within 48 hours of injury that failed to resolve a month post-injury; however, these costs did not generalize across the switching task types. Chronic TBI subjects performed internally generated and externally cued switching paradigms with a degree of success equivalent to that of healthy controls but displayed larger amounts of activation and recruited more areas of the brain at lower levels of difficulty and did not increase recruitment in a stepwise fashion at higher levels of difficulty. Mild TBI causes significant deficits in task switching, but there is specificity in these deficits. Chronic TBI patients performed at a level equivalent to that of controls but displayed different patterns and degree of activation. Taken together, these findings indicate that there may be a specific time frame during which task switching shows behavioral deficits, after which the subject may compensate for these deficits to produce normalized performance. / Committee in Charge: Dr. Paul van Donkelaar, Chair; Dr. Li-Shan Chou; Dr. Ulrich Mayr; Dr. Marjorie Woollacott

Transition from elementary to middle or junior high schools has been associated with slowed reading and mathematics achievement for students in general education as well as students with disabilities. Little is known about how this transition affects students with autism spectrum disorder (ASD), traumatic brain injury (TBI), or emotional/behavioral disturbance (EBD). Reading and math scores from state achievement tests used for federal accountability reporting were analyzed from 125,646 Oregon students between 2006 and 2013. About half were female, about half qualified for free or reduced price lunch, and about 34% identified as an ethnic or racial minority. Piecewise longitudinal growth models were analyzed using hierarchical linear and nonlinear modeling, separately for reading and math achievement. Scores for all students, on average, rose slightly faster before transition than after transition. Students who experienced a school transition in Grade 6 were more negatively impacted than those who transitioned in Grade 7, while students who stayed in the same school from Grade 3 to 8 experienced the least impact. Initial scores in reading and math for students with ASD were lower than students without disabilities; students with EBD were lower still, and students with TBI had the lowest. Before transition, students with ASD and EBD accelerated faster in reading than students without disabilities whereas in math, students with ASD or EBD showed improved scores immediately after transition. Students with EBD maintained post-transition trajectories similar to students without disabilities. Students with EBD had the most pronounced deceleration in reading scores after the transition whereas students with TBI had the most deceleration in math.

abstract: Traumatic brain injury (TBI) most frequently occurs in pediatric patients and remains a leading cause of childhood death and disability. Mild TBI (mTBI) accounts for 70-90% of all TBI cases, yet its neuropathophysiology is still poorly understood. While a single mTBI injury can lead to persistent deficits, repeat injuries increase the severity and duration of both acute symptoms and long term deficits. In this study, to model pediatric repetitive mTBI (rmTBI) we subjected unrestrained juvenile animals (post-natal day 20) to repeat weight drop impact. Animals were anesthetized and subjected to sham or rmTBI once per day for 5 days. At 14 days post injury (PID), magnetic resonance imaging (MRI) revealed that rmTBI animals displayed marked cortical atrophy and ventriculomegaly. Specifically, the thickness of the cortex was reduced up to 46% beneath and the ventricles increased up to 970% beneath the impact zone. Immunostaining with the neuron specific marker NeuN revealed an overall loss of neurons within the motor cortex but no change in neuronal density. Examination of intrinsic and synaptic properties of layer II/III pyramidal neurons revealed no significant difference between sham and rmTBI animals at rest or under convulsant challenge with the potassium channel blocker, 4-Aminophyridine. Overall, our findings indicate that the neuropathological changes reported after pediatric rmTBI can be effectively modeled by repeat weight drop in juvenile animals. Developing a better understanding of how rmTBI alters the pediatric brain may help improve patient care and direct "return to game" decision making in adolescents. / Dissertation/Thesis / Masters Thesis Biology 2014

abstract: Modern medical conditions, including cancer, traumatic brain injury, and cardiovascular disease, have elicited the need for cell therapies. The ability to non-invasively track cells in vivo in order to evaluate these therapies and explore cell dynamics is necessary. Magnetic Resonance Imaging provides a platform to track cells as a non-invasive modality with superior resolution and soft tissue contrast. A new methodology for cellular labeling and imaging uses Nile Red doped hexamethyldisiloxane (HMDSO) nanoemulsions as dual modality (Magnetic Resonance Imaging/Fluorescence), dual-functional (oximetry/ detection) nanoprobes. While Gadolinium chelates and super paramagnetic iron oxide-based particles have historically provided contrast enhancement in MRI, newer agents offer additional advantages. A technique using 1H MRI in conjunction with an oxygen reporter molecule is one tool capable of providing these benefits, and can be used in neural progenitor cell and cancer cell studies. Proton Imaging of Siloxanes to Map Tissue Oxygenation Levels (PISTOL) provides the ability to track the polydimethylsiloxane (PDMS) labeled cells utilizing the duality of the nanoemulsions. 1H MRI based labeling of neural stem cells and cancer cells was successfully demonstrated. Additionally, fluorescence labeling of the nanoprobes provided validation of the MRI data and could prove useful for quick in vivo verification and ex vivo validation for future studies. / Dissertation/Thesis / Masters Thesis Bioengineering 2014

abstract: According to sources of the Centers for Disease Control and Prevention, approximately 1.7 million traumatic brain injury (TBI) cases occur annually in the United States. TBI results in 50 thousand deaths, nearly 300 thousand hospitalizations and 2.2 million emergency room visits causing a $76 billion economic burden in direct and indirect costs. Furthermore, it is estimated that over 5 million TBI survivors in the US are struggling with long-term disabilities. And yet, a point-of-care TBI diagnostic has not replaced the non-quantitative cognitive and physiological methods used today. Presently, pupil dilation and the Glasgow Coma Scale (GCS) are clinically used to diagnose TBI. However, GSC presents difficulties in detecting subtle patient changes, oftentimes leaving mild TBI undiagnosed. Given the long-term deficits associated with TBIs, a quantitative method that enables capturing of subtle and changing TBI pathologies is of great interest to the field. The goal of this research is to work towards a test strip and meter point-of-care technology (similar to the glucose meter) that will quantify several TBI biomarkers in a drop of whole blood simultaneously. It is generally understood that measuring only one blood biomarker may not accurately diagnose TBI, thus this work lays the foundation to develop a multi-analyte approach to detect four promising TBI biomarkers: glial fibrillary acidic protein (GFAP), neuron specific enolase (NSE), S-100β protein, and tumor necrosis factor-α (TNF-α). To achieve this, each biomarker was individually assessed and modeled using sensitive and label-free electrochemical impedance techniques first in purified, then in blood solutions using standard electrochemical electrodes. Next, the biomarkers were individually characterized using novel mesoporous carbon electrode materials to facilitate detection in blood solutions and compared to the commercial standard Nafion coating. Finally, the feasibility of measuring these biomarkers in the same sample simultaneously was explored in purified and blood solutions. This work shows that a handheld TBI blood diagnostic is feasible if the electronics can be miniaturized and large quantity production of these sensors can be achieved. / Dissertation/Thesis / Doctoral Dissertation Biomedical Engineering 2017

abstract: Military veterans have a significantly higher incidence of mild traumatic brain injury (mTBI), depression, and Post-traumatic stress disorder (PTSD) compared to civilians. Military veterans also represent a rapidly growing subgroup of college students, due in part to the robust and financially incentivizing educational benefits under the Post-9/11 GI Bill. The overlapping cognitively impacting symptoms of service-related conditions combined with the underreporting of mTBI and psychiatric-related conditions, make accurate assessment of cognitive performance in military veterans challenging. Recent research findings provide conflicting information on cognitive performance patterns in military veterans. The purpose of this study was to determine whether service-related conditions and self-assessments predict performance on complex working memory and executive function tasks for military veteran college students. Sixty-one military veteran college students attending classes at Arizona State University campuses completed clinical neuropsychological tasks and experimental working memory and executive function tasks. The results revealed that a history of mTBI significantly predicted poorer performance in the areas of verbal working memory and decision-making. Depression significantly predicted poorer performance in executive function related to serial updating. In contrast, the commonly used clinical neuropsychological tasks were not sensitive service-related conditions including mTBI, PTSD, and depression. The differing performance patterns observed between the clinical tasks and the more complex experimental tasks support that researchers and clinicians should use tests that sufficiently tax verbal working memory and executive function when evaluating the subtle, higher-order cognitive deficits associated with mTBI and depression. / Dissertation/Thesis / Doctoral Dissertation Speech and Hearing Science 2017