Traumatic brain injury (TBI) affects 1.4 million people a year in the United States alone and despite the fact that 96% of people survive a TBI, the health and socioeconomic consequences can be grave, partially due to the fact that very few clinical treatments are available to reduce the damage and subsequent dysfunction following TBI. To better understand the various mechanical, electrical, and chemical events during neural injury, and to elucidate specific cellular events and mechanisms that result in cell dysfunction and death, new high-throughput models are needed to recreate the environmental conditions during injury. This thesis project focuses on the creation of a novel and clinically relevant single-cell injury model of traumatic brain injury (TBI). The implementation of the model requires the development of a novel injury device that allows specialized micro-interfacing functionality with neural micro environments, which includes the induction of prescribed strains and strain rates onto neural tissue, such as groups of cells, individual cells, and cell processes. The device consists of a high-resolution micro-electro-mechanical-system (MEMS) microtweezer microactuator tool that is introducible into both biological and aqueous environments and can be proximally positioned to specific targets in neural tissue and neural culture systems. This microtweezer, which is constructed using traditional photolithography and micromachining processes, is controllable by a custom developed software-automated controller that incorporates a high precision linear actuator and utilizes a luer-based microtool docking interface. The injury studies will include examination of intracellular calcium concentration over the injury time course to evaluate neuronal plasma membrane permeability, which is a significant contributor to secondary injury cascades following initial mechanical insult. Mechanical strain and strain rate input tolerance criteria will also be used to determined thresholds for cellular dysfunction and death.

Falls among the elderly population continue to be a growing concern in the healthcare industry and are marked by staggeringly high social and economic costs. The incidence of falls is known to increase with age, and currently the elderly population is growing at an astounding rate as baby-boomers are now entering this age group. Also, recovery following fall-related injuries decreases with increased age. These confounding factors currently make falls a very important area of research. Of the injuries typically seen in falls among the elderly, head injuries are one of the most debilitating. Death due to head trauma among the elderly is gaining national attention; head trauma is now considered the number one cause of death among elders who fall1. Among other technologies, medical helmets are often employed to protect against such injuries, but patient compliance with these helmets remains an issue. Current helmets use foams and cotton as padding, contributing to clumsy designs. Dilatent and honeycomb materials may be the future of this industry as their low weight and high efficacy per thickness make them ideal materials for thinner, lighter, less cumbersome head protection devices. This study outlines various modes of head injury and then highlights several head protection measures. The newer materials are tested using various methods to determine the most promising candidates for prototype designs. Next, three prototypes are assembled from the newer materials and compared directly based on the protection measures established. Finally, the top-performing prototype is compared against two existing medical helmets in a similar fashion. The results show that the best prototype significantly outperforms one of the existing medical helmets, and shows slight improvement over the other. These results establish the promise of these newer materials in the application of head protection devices.

The purpose of the present study was to explore the ways that spouses of persons with ABI experience a process of change in roles, routine, and overall lifestyle and the subsequent implications for their support needs. The present study used a qualitative narrative inquiry methodology to examine the process of the experiences of this population of spouses. In-depth semi-structured interviews were conducted with 15 spouses, each of whom was engaged in a heterosexual relationship. There were 10 female and five male participants whose ages ranged from 40 to 61. Twelve of the participants were formally married, and three were in a common law relationship. In the interviews, the participants were asked about the changes in their lives after the onset of their spouses’ brain injuries. The data analysis was informed by narrative inquiry with attention paid to the structure of the participants’ stories. A three phase trajectory of caregiving emerged from the analysis which provided details regarding the process of change in the spousal caregiving role and how various role transitions within this role were intertwined with stressors and other feelings. The research highlighted three phases of caregiving including an Embryonic, Immersed and Modified Caregiver phase. The findings were theoretically important for identifying: how these spouses situate themselves within role transitions; coping strategies; various support needs; and future directions for research in this area.

The purpose of the present study was to explore the ways that spouses of persons with ABI experience a process of change in roles, routine, and overall lifestyle and the subsequent implications for their support needs. The present study used a qualitative narrative inquiry methodology to examine the process of the experiences of this population of spouses. In-depth semi-structured interviews were conducted with 15 spouses, each of whom was engaged in a heterosexual relationship. There were 10 female and five male participants whose ages ranged from 40 to 61. Twelve of the participants were formally married, and three were in a common law relationship. In the interviews, the participants were asked about the changes in their lives after the onset of their spouses’ brain injuries. The data analysis was informed by narrative inquiry with attention paid to the structure of the participants’ stories. A three phase trajectory of caregiving emerged from the analysis which provided details regarding the process of change in the spousal caregiving role and how various role transitions within this role were intertwined with stressors and other feelings. The research highlighted three phases of caregiving including an Embryonic, Immersed and Modified Caregiver phase. The findings were theoretically important for identifying: how these spouses situate themselves within role transitions; coping strategies; various support needs; and future directions for research in this area.

Introduction: Mild traumatic brain injury (mTBI) accounts for the vast majority of all paediatric TBI cases. It is an important public health concern, yet the long-term psychiatric and behavioural outcomes remain imperfectly understood. Aim. This study aims to examine the association between paediatric mTBI and psychiatric and offending outcomes in adulthood, while considering the impact of sex, age at injury and duration since injury on outcome. Participants: Participants with mTBI (n=57) were compared to those with moderate/severe TBI (n=62) and to orthopaedic injury controls (n=42). All participants were injured at age 17 or younger and were 18 years or older at the time of assessment. Outcome measures: Based on the DSM-IV-TR criteria, structured interviews were used to assess participants’ experience of symptoms consistent with major depressive disorder, anxiety disorders (including generalised anxiety disorder, panic attacks and panic disorder, agoraphobia, social phobia, post-traumatic stress disorder, and specific phobia), and substance abuse and/or dependence. Participants’ were asked to report on their lifetime involvement with offending, arrests, and diversions and/or convictions. Results: At age 18-31, participants with a paediatric mTBI were significantly more likely than orthopaedic injury controls to endorse symptoms consistent with major depressive disorder by 3.17 times, anxiety disorders by 5.81 times, and internalising disorders in general by 5.80 times and the risk in the mTBI group was greater than that for those with moderate/severe TBI. Females with mTBI were significantly more likely than males, by five times, to endorse an internalising disorder. Paediatric mTBI was not significantly associated with externalising problems when compared with controls; however, males with mTBI were 6.57 times more likely to endorse externalising behaviours than females. Conclusions: Paediatric mTBI is a risk factor for internalising disorders in adulthood, particularly for females. Such findings have implications for assessment and treatment of problems associated with paediatric mTBI.

Functional magnetic resonance imaging (fMRI) is a relatively new tool that has been used to examine patterns of neural activation within those with traumatic brain injuries (TBI). A review of relevant literature is presented, including alterations in activity within the frontal and parietal regions that are thought to be compensatory in nature. In addition, possible explanations for discrepancies within this research are discussed. The current study expands upon previous work by incorporating a delayed-match-to-sample (DMS) task within an event-related paradigm and neuropsychological testing to compare 12 individuals with a history of TBI to 12 control participants with orthopedic injuries (OI). Participants in the TBI group were high functioning and in the chronic stage of recovery. Neuropsychological testing revealed statistically significant group differences in measures of working memory, processing speed, memory, and executive functioning. However, groups were comparable in accuracy on the DMS task. Percent signal changes in fMRI data revealed statistically significantly increased activation within the right dorsolateral prefrontal cortex (BA 46) for the TBI group compared to controls. Additional alterations in activation were found between groups within the inferior temporal (BA 37) and parietal (BA 7) regions. Regression analyses showed no relationship between neuropsychological testing and percent signal change within BA 46, but predictive relationships between testing and BA 37 and BA 7. Logistic regression analyses suggest that fMRI data did not add any incremental predictive value beyond neuropsychological testing alone when attempting to predict group (TBI vs. OI) membership.

Historically, there has been limited empirical study of children whose parents have suffered an acquired brain injury. This is despite the fact that both clinical opinion and qualitative study suggest that these children may represent a population at risk for a variety of emotional and behavioral problems. The current study set out to evaluate the overall psychosocial functioning of a small subset of children whose parents had suffered an acquired brain injury (TBI, stroke) and who were in the more chronic phase of recovery (average time post-injury = 3.3 years). Factors that have been proposed to impact child psychosocial functioning in this population were assessed including the neurobehavioral profile of the parent with an injury, parental depression, and the child’s report of the parental relationship. In all, ten children (average age = 13 years) from seven families with parental ABI were evaluated both on a comprehensive measure of child psychosocial functioning (BASC-2) and a series of qualitative measures. As compared to a normative sample, results of quantitative analyses suggest a group of children not experiencing general clinical distress. In fact, statistical analyses suggest resiliency in the current sample as compared to normative data. At the individual level, two of the children in the sample evidenced behavior that warrants further clinical evaluation, though this finding may be on par with the base rates of clinical distress seen in the general population. Qualitative analyses provide a richer understanding of the experiences of these children and their families and suggest avenues for further empirical evaluation. Results are presented in the context of other studies to date. Recommendations for clinicians and researchers based on current findings are provided. / Graduate / 0622 / rlillie@uvic.ca

Psychosocial factors represent complex and enduring challenges for people with a traumatic brain injury (TBI), their families and health and rehabilitation systems, particularly in relation to social isolation, change/loss of role and identity issues. Traditional rehabilitation approaches to psychosocial issues target cognitive rehabilitation and psychological adjustment of the individual with a TBI, which reflect the medical model of health. However, the International Classification of Functioning, Disability and Health (ICF) ushers a new era in TBI research and practice, which advances the conceptualisation of disability, to include the impact of environmental factors. The ICF identifies the Internet as one such environmental factor, which has the potential to facilitate or impede social participation of people with a disability. Empirical studies suggest the potential of the Internet to empower people with disabilities, via opportunities for social connection; social support; social role participation and identity experimentation. However, research has focused on people with sensory, physical, and mental health issues, with little known of the potential of the Internet for people with a TBI. This area of deficit warrants investigation, in view of the potential of the Internet to address many dimensions of psychosocial concern following TBI. This study explores the role of the Internet in the lives of people with a TBI, with a focus on the potential of the Internet to influence psychosocial recovery. Psychosocial recovery is conceptualised as the reconstruction of a positive identity, as found in subjective accounts of people with a TBI (Lewington, 1996), and strongly supported in the mental health consumer literature. Using a social constructionist approach, this study explores how people with a TBI use the Internet and how they make meaning of their Internet experience. This approach acknowledges the socially situated nature of Internet use and validates the subjective accounts of people with a TBI, whose perspectives are underrepresented in the rehabilitation literature. This study also trials the method of email-facilitated qualitative interviewing, to address face-to-face interviewing barriers, relating to cognitive-linguistic impairments (Lloyd, Gatherer, & Kalsy, 2006; Paterson & Scott-Findley, 2002). Thus, the Internet is the focus of the enquiry and the mediator of the method. The findings highlight the positive potential of the Internet to facilitate social participation for people with a TBI. Participants reported that features such as asynchronicity, reduced cues and anonymity made the Internet an accessible and usable technology, for social connection; social support; social role participation and identity reconstruction. A major theme emerging from the data was control of self, which this study conceptually linked to identity reconstruction and psychosocial recovery. Findings allayed concerns regarding the negative potential of the Internet to increase social isolation of vulnerable people, as participants regarded face-to-face relationships as more fulfilling than online friendships, supporting classic communication theories (Rice, 1987; Rice & Love, 1987), which propose that the Internet is a less personal medium than face-to-face communication, due to the feature of reduced cues. The findings of the method indicated that email facilitated qualitative interviewing addressed face-to-face interviewing barriers related to cognitive linguistic impairments; mobility factors; chronic health issues and environmental stimuli. Most participants indicated that asynchronicity, reduced cues, and anonymity facilitated control of communication, cognition and identity, thus enabling interview participation. The method had also advantages for the researcher, including time for reflection and the ability to yield richer data than in face-to-face contexts. However, the method was resource intensive, requiring information technology proficiency, familiarly with the impact of cognitive-linguistic impairments in online contexts and counselling experience. In addition, ethical guidelines required the involvement of a support person for the emotional protection of participants. This study makes two contributions to knowledge. One contribution relates to the potential of the Internet as an ICF environmental factor to address long-term psychosocial concerns, in addition to positively influencing psychosocial recovery from TBI, as reported by participants. This study contributes to a new era of research, which considers the impact of environmental factors on the experience of TBI, as framed by the ICF. The second contribution relates to the method of email facilitated qualitative interviewing, which advances knowledge of interviewing barriers for people with a TBI and addresses calls for innovative methods with this population. The findings of the method bring into question long held assumptions about the capacity of people with a TBI to participate in research and have implications for research design in qualitative and quantitative methodologies.

Total body irradiation is the irradiation of the entire patient as a conditioning for bone marrow transplants. The conditioning process involves destroying the bone marrow allowing for repopulation of the donor bone marrow cells, suppression of the immune system to allow stop graft rejection, and to eliminate the cancer cell population within the patient. Studies have been done demonstrating the importance of TBI conditioning for BMT5. A range of TBI treatment techniques exist, this department uses a bi-lateral technique which requires bolus packed around the patient to simplify the geometry of the treatment. This investigation will focus on one technique which involves using a translating bed. This technique effectively scans a radiation beam over the patient as the bed moves through the beam. Other investigations on translating beds concentrated on varying the scan speed to achieve a dose uniformity to within ±5%. The recommendations quote a dose uniformity of +5% and -10% as acceptable⁹. The dose uniformity in these investigations was along the midline in the longitudinal direction only. This investigation varied field size to achieve dose uniformity to within ±2.5% along the midline of an anthropomorphic phantom. The goal was to determine if a dynamic multi-leaf collimator could be used to give a uniform in the transverse direction as well as the longitudinal direction. An advantage of utilizing the DMLC for this treatment is the ability to shield organs at risk, i.e. lungs and kidneys, without requiring resources to produce shielding blocks14. Gafchromic-EBT film18 was used as a dosimeter but gave unreliable results due to the lack of film scanning equipment with an appropriate sensitivity for reading the dose to the film. Scans were simulated using Xio treatment planning software. The results from the simulations gave a more reliable indication of the absorbed dose to the midline of the phantom. The disadvantage of this varying field size technique was the time and complexity involved in creating a treatment plan. Within the Xio software exists a limit on the number of beams allowed to be applied in a single plan. There is a maximum of 99 beams allowed which is not enough for complete coverage of a patient. A way around this is to increase the field sizes and decrease the scan speed. This option was not investigated. The advantage of this technique was the increased dose uniformity (±2.5%) in comparison to the varying scan speed techniques (±5%). This technique also allows the patient to be unencumbered during the treatment making the process more comfortable for them.

This study examined the efficacy of continuous nicotinamide (NAM) administration on recovery of function in rats following traumatic brain injury (TBI). TBI was induced via controlled cortical impact (CCI) bilaterally in the prefrontal cortex (+1.5, 0.0 relative to bregma) or sham surgeries were performed. Rats were then treated with either NAM (150 mg/kg/day) or vehicle (saline). Rats were tested behaviorally on the bilateral tactile adhesive removal task, locomotor placing task, novel exploratory behavior and the Morris water maze (MWM). Rats were also assessed histologically by looking at lesion size, GFAP expression (as a measure of active astroctyes) and MMP-9 expression (as a measure of inflammatory response) at time points of 24 and 48 hours and 30 days. The behavioral assessments showed significant improvements in the NAM-treated animals on the bilateral tactile adhesive removal, locomotor placing and MWM. The histological assessments showed significant lesion reduction at 30 days in the NAM-treated group. There were no differences between NAM-treated and vehicle groups on either GFAP or MMP-9 expression. These results indicate that NAM treatment after TBI can significantly improve recovery of function in rats.