Brain injury has a tremendous effect on the United States. The medical system has a continuum of care available but many of these services are extremely expensive. Despite the effectiveness of residential post-acute brain injury rehabilitation (PABIR) resistance to provide adequate funding remains because of a dearth of randomized controlled trial (RCT) studies demonstrating effectiveness. Some research suggests observational trials are typically more representative of community samples and yield conclusions similar to RCT studies. This study uses a large multi-state naturalistic community-based sample of individuals who received residential PABIR. The purposes of this study were to (1) use logistic regression to identify a model that considered the relationships among the predictor variables to explain treatment outcome for individuals receiving residential PABIR and (2) better understand how self-awareness influences treatment outcome. The final model contained five independent variables (substance use at time of admit, functioning level at time of admit, change in awareness between discharge and admit, admit before or after 6 months post-injury (TPI), and length of stay (LOS) in the program less than or greater than 2 months). The model was statistically significant, ÷2 (5, N=434) = 194.751, p < .001, accounting for 36.2% (Cox & Snell R square) to 61.3% (Nagelkerke R square) of the variance in success rate, and correctly classified 89.4% of cases. Four of the five predictor variables (current substance use, change in awareness, LOS 2 months and TPI 6 months) made statistically significant contributions to the model. The strongest predictor of successful treatment outcome was change in awareness recording an odds ratio of 29.9 indicating that individuals who improved in self-awareness by at least one level were nearly 30 times more likely to be in the successful outcome group, controlling for other factors in the model. Participants were also more likely to be in the successful outcome group if they admitted within 6-months post-injury (5.5x) and stayed longer than 2-months (4.4x). Findings also suggest that active substance use at time of admission did not prevent people from being successful. Importance and implications of these findings are discussed.

It has been postulated that there could be a connection between traumatic brain injury (TBI) and motor neuron disease (MND), including amyotrophic lateral sclerosis (ALS). As chronic traumatic encephalopathy (CTE) is caused by repeated TBI and is a newly examined disease, there has been little evaluation of the potential relationship between CTE and ALS. It was proposed that CTE is a risk factor for not only MND, but also ALS. There is significant evidence that even a single TBI is a risk factor for Parkinson's disease (PD), thought to be invoked by the inflammatory process that the brain undergoes following a TBI. General rigorous physical activity with trauma to the trunk or extremities does not appear to be a risk factor for ALS. However, physical activity with associated head traumas, especially repeated head traumas, does seem to increase the likelihood of developing ALS. The biological mechanism for this is suspected to be increase in free radicals during exercise in individuals who are predisposed to decreased antioxidant function. Additionally, individuals who have suffered repeated head trauma, even amongst the general population in a non-athletic setting, has been shown to drastically increase the individual's chance of developing ALS. CTE, which is most common in athletes, is speculated to be caused by TAR DNA-binding protein 43 (TDP-43), tau neurofibrillary tangle (NFT), and beta-amyloid (A-Beta) protein inclusions in brain tissue following a multitude of TBI during high level sport activity. There are individuals who suffer initially CTE, followed by ALS, indicating CTE is clearly a risk factor for ALS. Anatomically, the TDP-43, NTF, and A-Beta; inclusions are present in the brain tissue of both individuals with CTE alone as well as the individuals with CTE and ALS. The anatomic difference between these two pathologies is the inclusion of these three proteins in the spinal cord of ALS patients as well. Unfortunately, there are indications that previous studies of professional athletes and their development of ALS have presented with significant issues including confounding factors of the subpopulation and sample sizing. Additionally, the anatomical cause of TBI leading to ALS is still unknown. Further evaluation on the relationship between head injury and ALS must be dedicated to investigating the mechanism involved in developed PD versus ALS following TBI. The biologic sequence following TBI that leads to ALS must be examined and compared to individuals whom develop ALS but did not suffer TBI. Moreover, an assessment must be made to determine what causes some individuals to develop protein inclusions solely in the brain tissue, leading to CTE, and some individuals to have an advancement of the protein inclusions into the spinal cord, leading additionally to CTE followed by ALS.

The understanding and treatment of brain disorders as well as the development of intelligent machines is hampered by the lack of knowledge of how the brain fundamentally functions. Over the past century, we have learned much about how individual neurons and neural networks behave, however new tools are critically needed to interrogate how neural networks give rise to complex brain processes and disease conditions. Recent innovations in molecular techniques, such as optogenetics, have enabled neuroscientists unprecedented precision to excite, inhibit and record defined neurons. The impressive sensitivity of currently available optogenetic sensors and actuators has now enabled the possibility of analyzing a large number of individual neurons in the brains of behaving animals. To promote the use of these optogenetic tools, this thesis integrates cutting edge optogenetic molecular sensors which is ultrasensitive for imaging neuronal activity with custom wide field optical microscope to analyze a large number of individual neurons in living brains. Wide-field microscopy provides a large field of view and better spatial resolution approaching the Abbe diffraction limit of fluorescent microscope. To demonstrate the advantages of this optical platform, we imaged a deep brain structure, the Hippocampus, and tracked hundreds of neurons over time while mouse was performing a memory task to investigate how those individual neurons related to behavior. In addition, we tested our optical platform in investigating transient neural network changes upon mechanical perturbation related to blast injuries. In this experiment, all blasted mice show a consistent change in neural network. A small portion of neurons showed a sustained calcium increase for an extended period of time, whereas the majority lost their activities. Finally, using optogenetic silencer to control selective motor cortex neurons, we examined their contributions to the network pathology of basal ganglia related to Parkinson’s disease. We found that inhibition of motor cortex does not alter exaggerated beta oscillations in the striatum that are associated with parkinsonianism. Together, these results demonstrate the potential of developing integrated optogenetic system to advance our understanding of the principles underlying neural network computation, which would have broad applications from advancing artificial intelligence to disease diagnosis and treatment.

Chronic Traumatic Encephalopathy (CTE) has been linked to contact sports, most notably boxing and American football, due to their propensity for repetitive head impacts. Concerns in the community for the safety of athletes in all contact sports has driven a significant amount of research into concussions, their long term effects, and strategies for treatment and prevention. Knowledge of long term brain health in response to neurotrauma is limited, a gap especially noticeable in the literature on non-catastrophic brain injuries sustained as a child. Concussion is a common injury that is often self-resolving with no lasting neurologic or cognitive deficits. Although repetitive brain trauma is hypothesized to be necessary and sufficient to lead to CTE, no human or animal models have definitively demonstrated the pathophysiologic connection or confirmed the mechanism of symptoms. The research to date has been case based, lacking prospective cohorts, with data complicated by convenience sampling. These factors limit the generalizability of conclusions. CTE is neuropathologically defined with variable symptoms; however, it is only diagnosable at postmortem autopsy making the etiology and prevalence difficult to understand. As more research is published to understand if there is an association between a neurocognitive degenerative disease and contact sports, the concentration is on professional athletes. Yet professional athletes do not represent the overwhelming majority of all contact sport participants. The proposed study will compare adults who participated in youth football, but not beyond the high school level, to a control group of adults who did not play contact sports. Evaluating their cognitive function with an online assessment, the Behavior Rating Inventory of Executive Function – Adult Version (BRIEF-A), data will be analyzed for signs of clinical cognitive impairment. The objective is to measure adults who represent the high percentage of youth football players who do not continue to the advanced levels. Data obtained from this study will help communities make informed decisions, and create the foundation for future studies on long term benefits and risks of contact sports for children.

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.

xv, 162 p. ; ill. (some col.) A print copy of this thesis is available through the UO Libraries. Search the library catalog for the location and call number. / Each year, over 65,000 brain injury survivors are discharged home from hospitals with ongoing rehabilitation needs due to acquired impairments, such as dysphagia. Emerging empirical evidence supports the benefits of intensive swallowing exercise programs when dysphagia results from muscle weakness. However, many of these survivors cannot complete intensive home exercise programs due to co-occurring cognitive impairments in memory or initiation. This project investigated the potential benefits of a new experimental assistive technology device, the Television Assisted Prompting (TAP) system to increase completion of home swallowing exercises. The TAP system was designed as a treatment package to provide both automated prompts and multimedia motivational instructional exercise videos via a person's home television. Three participants were recruited, all of whom had survived a hemispheric stroke and presented with neurogenic dysphagia and co-occurring cognitive impairments. Two home program delivery conditions were alternately presented on randomized days in a single-case experimental alternating treatment design: TAP delivery (e.g., TV prompting with motivational videos) or typical practice (TYP) delivery (e.g., care provider prompting as needed to follow assigned written home programs). The same exercises were presented in each condition. Measures included feasibility (e.g., reliability of the TAP system), efficacy (e.g., number of exercises completed per session), and satisfaction. Results revealed that two of three participants showed dramatic benefits from the TAP system. Participant 1 was 17 times more likely to complete exercises when prompted by the TAP system; participant 2 was six times more likely. Participant 3 completed exercises with equal likelihood on TAP or TYP days. All three participants reported preference for TAP system delivery and requested to increase the frequency of TAP delivery to every day. Care providers unanimously reported preference for the TAP system to prompt patients and reduce their burden of care. The TAP system malfunctioned during 21.70% (23/106) of scheduled sessions; two participants needed clarifications, instruction to use the system, or customized modifications in order to interact independently with the device. Recommendations for system improvements and applications to the field of assistive technology are provided. / Adviser: McKay Moore Sohlberg

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

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.