Military personnel often experience mild traumatic brain injury (mTBI) from exposure to improvised explosive devices (IEDs). Soldiers typically endure blast trauma from the IED pressure wave as well as blunt trauma from ensuing head impacts. Researchers have not reached a consensus on whether the biomechanical response from blunt or blast trauma plays a more dominant role in mTBI because the specific biomechanical sources of injury are often undetermined. Consequently, the goal of this dissertation was to conduct three separate studies in order to characterize the mechanical behavior of the brain after exposure to mTBI conditions. For Study 1, mild blunt and blast trauma were induced in Sprague-Dawley rats using a custom-built device. In-house diffusion tensor imaging (DTI) software was used to make 3-D reconstructions of white matter fiber tracts before and after injury (1, 4, and 7 days). Axonal integrity was characterized by examining the fiber count, fiber length, and fractional anisotropy (FA). In-house image analysis software also quantified the microstructural variations in Hematoxylin and Eosin (H&E) stained brain sections, where significant differences in parameters such as the area fraction (AF) and nearest neighbor distance (NND) correlated to voids that formed after water diffused extracellularly from axons. Study 2 employed a computational approach involving the development of a finite element (FE) model for the rat head followed by the simulation of blunt and blast trauma, respectively. FE parameters such as von Mises stress, pressure, and maximum principal strain were analyzed at various locations including the skull, cerebral cortex, corpus callosum, and hypothalamus to compare injury cases. Study 3 involved interruption mechanical testing of porcine brain, a suitable animal surrogate of human brain. Compression, tension, and shear experiments were performed at a strain rate of 0.1 s-1 to examine the differential mechanical response. Microstructural changes in H&E stained brain sections were analyzed with in-house image analysis software to quantify differences among stress states at strains of 0.15, 0.30, and 0.40. Studies 1 and 2 confirmed that the brain behaves differently in response to blunt and blast trauma, respectively, while Study 3 further demonstrated the stress state dependent behavior of brain tissue.

Individuals with Traumatic Brain Injury (TBI) exhibit impaired performance on social cognition and theory of mind (ToM) measures, like the Video Social Inference Test (VSIT). The frontal lobe, being the primary region involved in higher level cognitive functions mediates the neural mechanisms involved in social cognition and ToM abilities, according to studies on brain and behaviour. The goal of this study was to examine if individuals with TBI who did not damage their frontal lobe would perform differently on the VSIT than individuals with TBI who did. This study was a secondary analysis of documented imaging data and VSIT scores obtained from 51 adults with moderate-to-severe TBI (23 females). A comparison was made between scores obtained on the VSIT between participants with and without frontal lobe lesions. The results indicated that there was no significant difference between the two groups, in other words, site of lesion in participants with TBI did not predict performance on the VSIT. The results suggest that while the VSIT may yield critical information about social cognition, it is not sensitive to individual site of lesion. There is evidence that aspects of social cognition are impaired in this clinical population, however, most research in this area is obstructed by the complex nature of TBI neuropathology in addition to small heterogenous samples involved in studies. Further research in this area is required in order to reveal and enhance our understanding of social cognition deficits following TBI. Keywords: social cognition, traumatic brain injury, theory of mind, frontal lobe lesions, video social inference test / Thesis / Master of Science (MSc)

<p>Traumatic brain injury (TBI) is characterized by a violent or sudden blow to the head that causes tearing or bruising of the brain tissue and its supporting blood vessels. Determination of the mechanical properties of gray and white matter is critical for the creation of computational models of healthy and TBI-damaged brain tissues. Current in vivo methods to characterize brain tissue, such as 3D amplified MRI (aMRI) and magnetic resonance elastography (MRE), are highly vulnerable to motion artifacts and have limited techniques to exert mechanical loads on the brain. Therefore, in vitro testing was employed to estimate the chemical composition of gray and white matter using Fourier Transform Infrared (FTIR) spectroscopy and the stress responses of the brain tissues to high compressive deformations via unconfined compression. Attenuated total reflectance (ATR) was run in conjunction with FTIR spectroscopy to eliminate the need for sample preparation. Unconfined compression of gray and white matter samples was performed to 70% of the total sample height at a constant strain rate of 0.35/s. Results showed significant increases in the absorbances of white matter (<em>p</em> < 0.05) in the characteristic lipid and carbohydrate regions of the FTIR spectra when compared to gray matter. Within the initial 10% toe-region of the stress-strain curve, white matter is observed to absorb significantly greater compressive loads (<em>p </em>< 0.05) than gray matter. These results indicate an incomplete characterization of brain tissue; therefore, additional in vitro and in vivo methods are still necessary, separately or in combination, to accurately characterize brain tissue mechanics in TBI and non-TBI patients.</p>

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24512号 / 医博第4954号 / 新制||医||1064(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 花川 隆, 教授 古川 壽亮, 教授 中本 裕士 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Historical redlining, a discriminatory practice of the 1930s, present-day social vulnerability (SVI), and sports and recreational injury (SRI) hospitalizations are interconnected topics that highlight the intersection of race, class, and health in the United States but the relationships have not been studied to date. Thus, the overall aim of this dissertation is to examine the effects of historical redlining and present-day social vulnerability on SRI hospitalizations in the United States. The first study systematically reviewed studies that examined the relationships between neighborhood characteristics and SRI using multilevel modeling approach. Studies reviewed show that certain neighborhood factors, such as living in urban communities, were associated with increased risk of SRI. The second study examined the association between historical redlining and present-day neighborhood SVI in the United States. Results show that formerly redlined areas have higher SVI presently. The third study examined the association between historical redlining and present-day SRI hospitalization in the United States. Results show that redlining was not associated with increased odds of SRI hospitalizations, but was associated with longer length of hospital stay (LOS) among Black and Hispanic patients, and higher total hospital charges among Hispanic patients. The fourth study examined the association between individual and neighborhood social vulnerability and sports and recreation-related traumatic brain injury (SR-TBI) hospitalizations among pediatric patients in the United States. Results show that Native American children had higher odds of hospitalization for SR-TBI, longer LOS, but lower odds of discharge to post-acute care compared to White children. Older age was associated with higher odds of hospitalization and longer LOS while male sex was associated with shorter LOS for SR-TBI in children. Compared to children with private insurance, children with public insurance had longer LOS while uninsured children had shorter LOS. Also, hospitalization in neighborhood with higher overall SVI was associated with longer LOS. This study advances our knowledge on the impact of structural racism on present-day SRI outcomes and will inform policy makers to prioritize health equity by addressing the underlying social determinants of health and the root causes of disparities in SRI outcomes. / Doctor of Philosophy / Every year, around 9 million people get hurt while playing sports or participating in recreational activities in the United States. Out of these, more than a third go to the emergency department for treatment, and several thousands need to stay in the hospital because their injuries are more serious. Even though only a small number of sports and recreational injuries (SRI) require hospitalization compared to those treated in the emergency department or outpatient clinics, these injuries tend to be more severe. They can cause significant harm to a person's physical, mental, and emotional well-being, and they also put a lot of pressure on the healthcare system and society as a whole. This dissertation assessed how historical discrimination against certain neighborhoods, called redlining, and present-day social vulnerability affect sports and recreational injury hospitalizations in the United States. This research found that the neighborhood where people live or are hospitalized matter for how often they are hospitalized for SRI, their length of stay in hospital, the amount of money they pay while in hospital, and how often they receive follow-up care after leaving hospital. While historical redlining was not directly linked to higher odds of hospitalization, it was associated with longer hospital stays for Black and Hispanic patients and higher costs for Hispanic patients. This research also found that children from socially vulnerable backgrounds were more likely to be hospitalized for sports-related traumatic brain injuries (SR-TBI) and stay in hospital longer, but were less like to receive follow-up care after leaving hospital. For instance, children from Native American backgrounds were three times more likely to be hospitalized for SR-TBI and stayed in the hospital 27% longer, but were 99.9% less likely to receive follow-up care after leaving hospital compared to White children. Also, children with public health insurance tended to have longer stays in hospital for SR-TBI compared to those with private health insurance. This research highlights how structural discrimination can impact health outcomes, and suggests that policymakers should address the root causes of health disparities in order to promote health equity.

There is an established bidirectional relation between substance use and traumatic brain injuries (TBIs). Despite the high rate of prescribing opioids for pain management following a TBI and the epidemic of opioid use disorder (OUD) in the United States, scarce research has specifically analyzed the association between TBI and OUD. In a series of three interrelated manuscripts, the present study will first examine the prevalence and features of TBIs among persons seeking treatment for OUD. Next, the present study will evaluate the association between TBI and indicators of risky health behaviors and OUD severity, including the risk of overdose and polysubstance use. The predictive ability of symptoms of posttraumatic stress disorder, anxiety, impulsivity, depression, and chronic pain on odds of having had a TBI will also be calculated. Last, a systematic review will be conducted to provide comprehensive guidelines for effective methods of tailoring OUD treatment to mitigate the effects of TBI on treatment outcomes. Altogether, the findings will aid in the understanding of the development of TBI for persons with OUD, provide insight into common clinical complexities for patients with OUD and TBI, and offer guidance on how best to tailor interventions to increase substance use treatment efficacy for persons with TBI.

Indiana University-Purdue University Indianapolis (IUPUI)

Background: People who have experienced a moderate or severe traumatic brain injury (TBI) will most likely live with motor and cognitive deficits including balance and poor mobility. These deficits may lead to limitations in activity participation, life satisfaction, and may increase the risk of falls. Improving access to rehabilitation care in the chronic phase of recovery is essential to prevent ongoing health issues. However, geographical restrictions, cost of transportation, or recently the COVID-19 pandemic restrictions may limit access to rehabilitation services. Telerehabilitation could serve as an alternative method to provide rehabilitation care while increasing access. Objectives: The overall objective of this dissertation was to understand the implementation of high-intensity telerehabilitation exercise programs for people living with a moderate or severe TBI and their family partners. This was accomplished by 1) determining the feasibility of using telerehabilitation, 2) investigating the effectiveness of high-intensity home-based telerehabilitation exercise programs on physical activity, functional mobility and dynamic balance, 3) understanding the perspectives and lived experiences of completing a telerehabilitation program, and 4) exploring how interpersonal behaviours can influence practice and be perceived in a telerehabilitation setting. Methodology: Influenced by a people-centered approach and explained by the Self-Determination Theory, this dissertation followed a mixed-method alternating single-subject design methodology. Five dyads composed of five persons living with a moderate or severe TBI and their family partners completed two high-intensity telerehabilitation programs remotely supervised, daily and weekly. The feasibility and effectiveness of the telerehabilitation programs were measured from a quantitative and qualitative perspective to replicate the clinical realities and understand all perspectives. Results: In this dissertation, the feasibility of using telerehabilitation with this population was highlighted by reporting high adherence, high usability, active engagement and safety. The effectiveness on physical activity levels, functional mobility, dynamic balance and concerns with falling was also demonstrated with no differences between the daily and weekly remote supervision schedule. The dyads described being highly satisfied, engaged, and enjoyed the remotely supervised exercise programs. The individuals with the TBI perceived more supportive behaviours than thwarting behaviours from the physiotherapist. Conclusion: This dissertation advances knowledge on telerehabilitation implementation for people living with cognitive and motor deficits following a TBI. High-intensity home-based telerehabilitation programs were shown to be feasible and effective. I introduced the importance of assessing needs-supportive and needs-thwarting interpersonal behaviours in the telerehabilitation context. Integrating these novel telerehabilitation concepts within emerging telerehabilitation models of care could significantly impact long-lasting positive health outcomes for individuals living with a moderate or severe TBI.

No description available.

A mild traumatic brain injury (mTBI), commonly referred to as a concussion, is when the brain experiences an abrupt acceleration and/or deceleration that sends shock waves through the brain tissue, upsetting its structure and function. A mTBI is a heterogeneous condition with acute and chronic outcomes for patients. The chronic form of mTBI can lead to a wide range of neurological, behavioral, and cognitive symptoms. Critically, this injury is not defined by a simple process or pathophysiological event but rather biomechanical and neurological brain damage that can trigger highly complex physiological cascades. These further lead to a wide range of cellular, molecular, and functional changes that alter genes and associated metabolites. These changes, if specifically characterized, could be used to predict a patient’s outcome and recovery timeline. Recently, genetic studies showed that specific genotypes could increase an individual’s risk of more severe injury and impaired recovery following mTBI. Consequently, an improved understanding of gene alteration and genetic changes is necessary to develop personalized diagnostic approaches which can guide the design of novel treatments. The current study proposes utilizing bioinformatic tools, biological networks, and databases to identify potential genes and microRNAs associated with the mTBI in order to aid the early diagnosis of mTBI and track recovery for individual patients. With bioinformatic techniques, we were able to identify and compare genetic and epigenetic data associated with mTBI, as well as understand the various aspects of molecular changes after brain injury. Ultimately, we analyzed and cataloged the biological pathways and networks associated with this injury. A critical search of online bioinformatics databases was performed to determine interactions between mTBI-related genes, and relevant molecular processes. The major finding was that APOE, S100B, GFAP, BDNF, AQP4, COMT, MBP, UCHL1, DRD2, ASIC1, and CACNA1A genes were significantly associated with mTBI outcome. Those genes are primarily involved in different neurological tasks and neurological pathways such as neuron projection regeneration, regulation of neuronal synaptic plasticity, cognition, memory function, neuronal cell death and the dopaminergic pathway. This study predicted specific miRNAs linked to mTBI outcomes and candidate genes (hsa-miR-204-5p, hsa-miR-16-5p, hsa-miR-10a-5p, has-miR-218-5p, has-miR-34a-5p), and RNA-seq analysis on the GSE123336 data revealed that one miRNA found (hsa-miR-10a-5p) matched our predictions related to mTBI outcomes. Pathway analysis revealed that the predicted miRNA targets were mainly engaged in nervous system signaling, neuron projection and cell differentiation. These findings may contribute to developing diagnostic procedures and treatments for mTBI patients who are still experiencing symptoms, but validation of these genetic markers for mTBI assessment requires patient participation and correlation with advanced personalized MRI methods that show concussion related changes. / Thesis / Master of Applied Science (MASc) / Traumatic brain injury (TBI) is a highly prevalent neurological injury affecting millions of individuals globally. Mild TBI (mTBI), sometimes called concussion, makes up over 85% of TBI cases. A mTBI is a heterogeneous condition with acute and chronic outcomes for patients and involves complex cascades of cellular and molecular events that can lead to functional changes in genes and associated metabolites. In recent genetic studies, it has been shown that certain genotypes are associated with a higher risk of experiencing a more serious injury and a slower recovery after mTBI. These genes can be utilized as crucial biomarkers to predict how long it will take for a person to recover from a concussion. The purpose of this study was to find potential biomarkers that could help in the early detection of mTBI and the monitoring of individual patients’ recovery. It was hypothesized that genes and miRNAs (and their associated proteins) involved in neuronal body, axonal and myelin integrity and regeneration would be identified as important markers of severity.