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<p> Traumatic Brain Injury (TBI) is one of the most prevalent causes of injury in young adults,  and is a leading cause of hospitalization, disability, and even death. Although severe TBI can lead  to serious acute injury (such as brain hemorrhaging and skull fractures) and chronic disability, the vast majority (~80%) of TBIs are mild in nature, and do not present with such drastic symptoms.  As such, these mild TBIs may go undiagnosed or underreported. Without overt, acute symptoms,  mild TBIs may be particularly insidious as they are shown to correlate with increased risk of  chronic social and cognitive processing impairments, as well as the risk of developing  neurodegenerative diseases later in life. Additionally, many people who suffer TBIs, whether on  the sports field, field of battle, or even in everyday life, often are at increased risk of additional  TBIs, which likely increase the risk of life-long post injury complications. Given these risk factors,  there is a clear need to understand how mild TBIs affect the brain both acutely and chronically and  develop tactics to properly diagnose and treat mild injuries early.  In this dissertation, we argue for the potential use of Auditory Evoked Potentials (AEPs), a  clinically used noninvasive set of tests, as an effective route for improved diagnostics of mild TBIs.  To achieve this, we must first understand the relationship between underlying anatomical changes  and chronic deficits in mild injury. In blast induced TBIs, some of the most common sequalae,  both acutely and chronically, are auditory in nature. Temporary changes in hearing thresholds or  tinnitus are very common, but chronic impairments in more complex auditory processing tasks,  such as hearing speech-in-noise, are often reported as well. Although acute changes are likely due  to damage to the peripheral auditory system, there is mounting evidence suggesting damage to central auditory regions may play a clear role in chronic processing changes, however, this is still  poorly understood. Recent studies of concussions in sports medicine have found that impact  induced TBIs may produce long-term, but not acute, deficits in subtle auditory processing function  as well. Given its potential for ubiquitous damage following TBIs of multiple forms, understanding  the post-injury central auditory system can act as a window into the time-course and severity of  secondary biochemical changes and chronic processing issues seen following mild TBI.  Here we use a well-established rat blast TBI model to examine the acute and chronic time  course of auditory processing changes, as well as biochemical and anatomical changes. We show  a clear biphasic response of acute and chronic changes in auditory processing. Changes in  oxidative stress, inflammation, and inhibition/excitation show similar patterns within key regions  of the central auditory system (CAS), suggesting a link between AEP results and underlying  chronic damage. Our second objective was to design a more clinically relevant and consistent  animal model of free-range of motion impact induced TBI. Once developed, we examined similar  AEP and immunohistochemical tests to determine the degree of similarity of CAS changes in a  second form of TBI. Interesting, while AEP results suggest some long-term changes in auditory  processing, these were not identical to blast changes. Finally, we utilized a computational model  for axonal node damage to assess one method of potential damage resulting from the oxidative  stress changes post injury and provides a framework for future modeling techniques for improved  diagnosis and treatment. These results together suggest that AEPs have the potential to improve  diagnostics and monitoring tools in mild TBIs, regardless of injury type.  </p>

Studies have shown elementary teachers may not be well prepared to use technology in their classrooms. This study examines one elementary teacher’s feelings of technology self-efficacy (TSE), needs and pedagogical strategies when using the interactive whiteboard (IWB) to teach elementary science. It employed a single case study design, where the researcher and participant worked together during supportive professional development (PD) sessions. Data sources are twelve PD sessions, the Computer Technology Integration Survey (adapted for IWB use in the classroom), and two interviews, three in-class observations of IWB science lessons, and three lesson debriefs. Descriptive and thematic analysis show the participant’s TSE was positively influenced by the PD. Five factors were determined to influence TSE: the participant’s level of interest, attitude, experience with technology, student assistance, and familiarity with the setting. Teacher, contextual and IWB- level needs were explained. Pedagogical strategies for technology use based on interactive IWB features are also discussed. Findings could contribute to current trends in teacher PD, continuing education, and preservice teaching programs related to science teaching. / Plusieurs enseignants ne sont pas bien préparés pour utiliser la technologie en classe. En particulier, le tableau blanc interactif (TBI) n’est pas utilisé de façon optimale par les enseignants lorsqu’ils enseignent les sciences et la technologie à l’élémentaire. Cette thèse présente l’étude de cas unique d’une enseignante de l’élémentaire ayant cheminé dans un processus de développement professionnel (DP) pour l’aider à intégrer le TBI en sciences et technologie. Douze sessions de DP, un questionnaire sur l’efficacité avec le TBI (CTIS adapté), deux entrevues, trois sessions d’observation en classe et trois discussions sur les leçons constituent les sources de données. La participante est devenue plus confiante pour utiliser le TBI suite au DP. Elle a rehaussé son sentiment d’autoefficacité et accru son intérêt et sa connaissance du TBI. Elle a acquis des compétences techniques et une connaissance des contenus d’enseignement adaptés au TBI, bien que plusieurs besoins perdurent. Certaines stratégies pédagogiques avec le TBI expérimentées en classe par l’enseignante sont discutées. Cette thèse peut contribuer à fournir des pistes pour aider les enseignants au primaire à mieux intégrer le TBI en sciences et technologie, que ce soit lors de leur formation initiale à l’enseignement ou en cours d’emploi.

Thesis (MA)-- Stellenbosch University, 2014. / ENGLISH ABSTRACT: Family caregivers play a large role in the lives of traumatic brain injury (TBI) survivors. This study explored the experiences of family members who care for TBI survivors in the Western Cape. Emphasis was placed on the challenges and resources that were associated with the caregiving role. A qualitative exploratory research design was implemented, whereby thematic analysis was utilised to examine the semi-structured interviews that were conducted with 12 female family caregivers of TBI survivors. Several challenges emerged, namely trauma, consequences of a TBI, responsibilities, lack of support, unawareness, financial burden, emotional challenges and coping. Several resources were also identified, namely the road to recovery, social support, financial resource and coping. These findings suggest that although caregivers who care for a family member who sustained a TBI face several challenges through the caregiving task, these individuals have a number of resources that help them to cope. Interventions that focus on psycho-education have been identified as an important need amongst the participants of this study. In addition, the need for support groups were highlighted as an important way in which many of the challenges that these caregivers experience could be addressed. Caregivers also expressed a need for more active involvement of health care professionals with regard to the provision of guidance, empathy and information. It seems as if the caregivers view the relationship between themselves and the health care professionals involved in the treatment of their family member who sustained a TBI as very important. It was however evident from the findings of this study that the caregivers are generally not satisfied with the quality of the interaction between the health care professionals and themselves. This study’s findings serve as a basis for future research studies on the experiences of family caregivers of TBI survivors in the Western Cape. / AFRIKAANSE OPSOMMING: Gesinsversorgers speel ’n groot rol in die lewens van oorlewendes van traumatiese breinbeserings (TBB). Hierdie studie het die ervaringe van gesinsversorgers van TBB-oorlewendes in die Wes-Kaap verken. Die fokus is op die uitdagings en hulpbronne wat geassosieer word met die versorgingsrol. ’n Kwalitatiewe ontwerp is geïmplementeer, waarby tematiese analise gebruik is om die semigestruktureerde onderhoude van 12 vroulike gesinsversorgers van TBB-oorlewendes te bestudeer. Verskeie uitdagings het na vore gekom, naamlik trauma, gevolge van TBB, verantwoordelikhede, gebrek aan ondersteuning, onbewustheid, finansiële las, emosionele uitdagings en hantering. Die hulpbronne wat geïdentifiseer is, het die pad na herstel, sosiale ondersteuning, finansiële hulpbron en hantering ingesluit. Intervensies wat fokus op psigo-opvoeding is geïndentifiseer as ’n belangrike behoefte onder die deelnemers aan die studie. Hierbenewens is ook ’n behoefte aan ondersteuningsgroepe uitgelig as ’n belangrike wyse om die vele uitdagings wat hierdie versorgers ervaar aan te pak. Die versorgers het ook ’n behoefte ervaar aan meer aktiewe betrokkenheid van gesondheidskundiges ten opsigte van die voorsiening van leiding, empatie en inligting. Dit blyk dat versorgers die verhouding tussen hulself en die gesondheidskundiges betrokke by hul gesinslid met die TBB as belangrik beskou. Desnietemin blyk dit duidelik uit die bevindinge van hierdie studie dat versorgers oor die algemeen nie tevrede is met die kwaliteit van die interaksie tussen die gesondheidskundiges en hulself nie. Die bevindinge van hierdie studie dien as basis vir toekomstige navorsing oor die ervaringe van gesinsversorgers van TBB-oorlewendes in the Wes-Kaap.

L'être humain utilise trois systèmes sensoriels distincts pour réguler le maintien de la station debout: la somesthésie, le système vestibulaire, et le système visuel. Le rôle de la vision dans la régulation posturale demeure peu connu, notamment sa variabilité en fonction de l'âge, du type développemental, et des atteintes neurologiques. Dans notre travail, la régulation posturale induite visuellement a été évaluée chez des participants au développement et vieillissement normaux âgés de 5-85 ans, chez des individus autistes (développement atypique) âgés de 12-33 ans, ainsi que chez des enfants entre 9-18 ans ayant subi un TCC léger. À cet effet, la réactivité posturale des participants en réponse à un tunnel virtuel entièrement immersif, se mouvant à trois niveaux de vélocité, a été mesurée; des conditions contrôles, où le tunnel était statique ou absent, ont été incluses. Les résultats montrent que la réactivité (i.e. instabilité) posturale induite visuellement est plus élevée chez les jeunes enfants; ensuite, elle s'atténue pour rejoindre des valeurs adultes vers 16-19 ans et augmente de façon linéaire en fonction de l'âge après 45 ans jusqu'à redevenir élevée vers 60 ans. De plus, à la plus haute vélocité du tunnel, les plus jeunes participants autistes ont manifesté significativement moins de réactivité posturale comparativement à leurs contrôles; cette différence n'était pas présente chez des participants plus âgés (16-33 ans). Enfin, les enfants ayant subi un TCC léger, et qui étaient initialement modérément symptomatiques, ont montré un niveau plus élevé d'instabilité posturale induite visuellement que les contrôles, et ce jusqu'à 12 semaines post-trauma malgré le fait que la majorité d'entre eux (89%) n'étaient plus symptomatiques à ce stade. En somme, cela suggère la présence d'une importante période de transition dans la maturation des systèmes sous-tendant l'intégration sensorimotrice impliquée dans le contrôle postural vers l'âge de 16 ans, et d'autres changements sensorimoteurs vers l'âge de 60 ans; cette sur-dépendance visuelle pour la régulation posturale chez les enfants et les aînés pourrait guider l'aménagement d'espaces et l'élaboration d'activités ajustés à l'âge des individus. De plus, le fait que l'hypo-réactivité posturale aux informations visuelles chez les autistes dépende des caractéristiques de l'environnement visuel et de l'âge chronologique, affine notre compréhension des anomalies sensorielles propres à l'autisme. Par ailleurs, le fait que les enfants ayant subi un TCC léger montrent des anomalies posturales jusqu'à 3 mois post-trauma, malgré une diminution significative des symptômes rapportés, pourrait être relié à une altération du traitement de l'information visuelle dynamique et pourrait avoir des implications quant à la gestion clinique des patients aux prises avec un TCC léger, puisque la résolution des symptômes est actuellement le principal critère utilisé pour la prise de décision quant au retour aux activités. Enfin, les résultats obtenus chez une population à développement atypique (autisme) et une population avec atteinte neurologique dite transitoire (TCC léger), contribuent non seulement à une meilleure compréhension des mécanismes d'intégration sensorimotrice sous-tendant le contrôle postural mais pourraient aussi servir comme marqueurs sensibles et spécifiques de dysfonction chez ces populations. Mots-clés : posture, équilibre, vision, développement/vieillissement sensorimoteur, autisme, TCC léger symptomatique, réalité virtuelle. / Maintaining upright stance is essential for the accomplishment of several goal-directed behaviors, such as walking. Humans use three distinct sensory systems to regulate their posture: the somatosensory, the vestibular and the visual systems. The role of vision in postural regulation remains poorly understood, notably its variability across the life-span, developmental type and neurological insult. Hence, visually-driven postural regulation was examined in typically developing and aging participants (5-85 years-old), as well as in atypically developing individuals with autism (12-33 years-old) and in children having sustained mTBI (9-18 years-old). In order to do so, participants' postural reactivity was assessed in response to a fully immersive virtual tunnel moving at 3 different velocities; control conditions were also included wherein the tunnel was either static or absent. Results show that visually-induced postural reactivity was strongest in young children, then attenuated to become adult-like between 16-19 years of age, and started increasing again linearly with age after 45 years until becoming strong again around 60 years. Moreover, at the highest tunnel velocity, younger autistic participants showed significantly less postural reactivity compared to age-matched controls and young adults (16-33 years-old). Finally, children having sustained mTBI, who were initially moderately symptomatic, exhibited increased visually-induced instability compared to their matched controls up to 12 weeks post-injury, although most of them (89%) were no longer highly symptomatic. Altogether, this suggests the presence of an important transition period for the maturation of the systems underlying sensorimotor integration in postural control at around 16 years of age, and further sensorimotor changes after 60 years of age; this over-reliance on vision for postural regulation in childhood and late adulthood could guide the design of age-appropriate facilities/ activities. Furthermore, the fact that postural hypo-reactivity to visual information present in autism is contingent on both the visual environment and on chronological age, enhances our understanding of autism-specific sensory anomalies. Additionally, the fact that children with mTBI show balance anomalies up to 3 months post-injury, even when they are no longer highly symptomatic may be related to altered processing of dynamic visual information and could have implications for the clinical management of mTBI patients, since symptoms resolution is commonly used as a criterion for return to activities. Finally, results stemming from populations with atypical development (autism) and with so-called transient neurological insult (mild TBI) not only contribute to enhance our understanding of sensorimotor integration mechanisms underlying postural control, but could also consist of sensitive and specific markers of dysfunction in these populations. Keywords : posture, balance, vision, sensorimotor development/ aging, autism, symptomatic mTBI, virtual reality.

Background: The hippocampus and corpus callosum have been shown to be vulnerable in head injury. Various neuroimaging modalities and quantitative measurement techniques have been employed to investigate pathological changes in these structures. Cognitive and behavioural deficiencies have also been well documented in head injury. Aims: The aim of this research project was to investigate structural changes in the hippocampus and corpus callosum. Two different quantitative methods were used to measure physical changes and neuropsychological assessment was performed to determine cognitive and behavioural deficit. It was also intended to investigate the relationship between structural change and neuropsychology at 1 and 6 months post injury. Method: Forty-seven patients with head injury (ranging from mild to severe) had undergone a battery of neuropsychological tests and an MRI scan at 1 and 6 months post injury. T1-weighted MRI scans were obtained and analysis of hippocampus and corpus callosum was performed using region-of-interest techniques and voxel-based morphometry which also included comparison to 18 healthy volunteers. The patients completed neuropsychological assessment at 1 and 6 months post injury and data obtained was analysed with respect to each assessment and with structural data to determine cognitive decline and correlation with neuroanatomy. Results: Voxel-based morphometry illustrated reduced whole scan signal differences between patients and controls and changes in patients between 1 and 6 months post injury. Reduced grey matter concentration was also found using voxel-based morphometry and segmented images between patients and controls. A number of neuropsychological aspects were related to injury severity and correlations with neuroanatomy were present. Voxel-based morphometry provided a greater number of associations than region-of-interest analysis. No longitudinal changes were found in the hippocampus or corpus callosum using region-of-interest methodology or voxel-based morphometry. Conclusions: Decreased grey matter concentration identified with voxel-based morphometry illustrated that structural deficit was present in the head injured patients and does not change between 1 and 6 months. Voxel-based morphometry appears more sensitive for detecting structural changes after head injury than region- of-interest methods. Although the majority of patients had suffered mild head injury, cognitive and neurobehavioural deficits were evidenced by a substantial number of patients reporting increased anxiety and depression levels. Also, the findings of relationships between reduced grey matter concentration and cognitive test scores are indicative of the effects of diffuse brain damage in the patient group.

L'être humain utilise trois systèmes sensoriels distincts pour réguler le maintien de la station debout: la somesthésie, le système vestibulaire, et le système visuel. Le rôle de la vision dans la régulation posturale demeure peu connu, notamment sa variabilité en fonction de l'âge, du type développemental, et des atteintes neurologiques. Dans notre travail, la régulation posturale induite visuellement a été évaluée chez des participants au développement et vieillissement normaux âgés de 5-85 ans, chez des individus autistes (développement atypique) âgés de 12-33 ans, ainsi que chez des enfants entre 9-18 ans ayant subi un TCC léger. À cet effet, la réactivité posturale des participants en réponse à un tunnel virtuel entièrement immersif, se mouvant à trois niveaux de vélocité, a été mesurée; des conditions contrôles, où le tunnel était statique ou absent, ont été incluses. Les résultats montrent que la réactivité (i.e. instabilité) posturale induite visuellement est plus élevée chez les jeunes enfants; ensuite, elle s'atténue pour rejoindre des valeurs adultes vers 16-19 ans et augmente de façon linéaire en fonction de l'âge après 45 ans jusqu'à redevenir élevée vers 60 ans. De plus, à la plus haute vélocité du tunnel, les plus jeunes participants autistes ont manifesté significativement moins de réactivité posturale comparativement à leurs contrôles; cette différence n'était pas présente chez des participants plus âgés (16-33 ans). Enfin, les enfants ayant subi un TCC léger, et qui étaient initialement modérément symptomatiques, ont montré un niveau plus élevé d'instabilité posturale induite visuellement que les contrôles, et ce jusqu'à 12 semaines post-trauma malgré le fait que la majorité d'entre eux (89%) n'étaient plus symptomatiques à ce stade. En somme, cela suggère la présence d'une importante période de transition dans la maturation des systèmes sous-tendant l'intégration sensorimotrice impliquée dans le contrôle postural vers l'âge de 16 ans, et d'autres changements sensorimoteurs vers l'âge de 60 ans; cette sur-dépendance visuelle pour la régulation posturale chez les enfants et les aînés pourrait guider l'aménagement d'espaces et l'élaboration d'activités ajustés à l'âge des individus. De plus, le fait que l'hypo-réactivité posturale aux informations visuelles chez les autistes dépende des caractéristiques de l'environnement visuel et de l'âge chronologique, affine notre compréhension des anomalies sensorielles propres à l'autisme. Par ailleurs, le fait que les enfants ayant subi un TCC léger montrent des anomalies posturales jusqu'à 3 mois post-trauma, malgré une diminution significative des symptômes rapportés, pourrait être relié à une altération du traitement de l'information visuelle dynamique et pourrait avoir des implications quant à la gestion clinique des patients aux prises avec un TCC léger, puisque la résolution des symptômes est actuellement le principal critère utilisé pour la prise de décision quant au retour aux activités. Enfin, les résultats obtenus chez une population à développement atypique (autisme) et une population avec atteinte neurologique dite transitoire (TCC léger), contribuent non seulement à une meilleure compréhension des mécanismes d'intégration sensorimotrice sous-tendant le contrôle postural mais pourraient aussi servir comme marqueurs sensibles et spécifiques de dysfonction chez ces populations. Mots-clés : posture, équilibre, vision, développement/vieillissement sensorimoteur, autisme, TCC léger symptomatique, réalité virtuelle. / Maintaining upright stance is essential for the accomplishment of several goal-directed behaviors, such as walking. Humans use three distinct sensory systems to regulate their posture: the somatosensory, the vestibular and the visual systems. The role of vision in postural regulation remains poorly understood, notably its variability across the life-span, developmental type and neurological insult. Hence, visually-driven postural regulation was examined in typically developing and aging participants (5-85 years-old), as well as in atypically developing individuals with autism (12-33 years-old) and in children having sustained mTBI (9-18 years-old). In order to do so, participants' postural reactivity was assessed in response to a fully immersive virtual tunnel moving at 3 different velocities; control conditions were also included wherein the tunnel was either static or absent. Results show that visually-induced postural reactivity was strongest in young children, then attenuated to become adult-like between 16-19 years of age, and started increasing again linearly with age after 45 years until becoming strong again around 60 years. Moreover, at the highest tunnel velocity, younger autistic participants showed significantly less postural reactivity compared to age-matched controls and young adults (16-33 years-old). Finally, children having sustained mTBI, who were initially moderately symptomatic, exhibited increased visually-induced instability compared to their matched controls up to 12 weeks post-injury, although most of them (89%) were no longer highly symptomatic. Altogether, this suggests the presence of an important transition period for the maturation of the systems underlying sensorimotor integration in postural control at around 16 years of age, and further sensorimotor changes after 60 years of age; this over-reliance on vision for postural regulation in childhood and late adulthood could guide the design of age-appropriate facilities/ activities. Furthermore, the fact that postural hypo-reactivity to visual information present in autism is contingent on both the visual environment and on chronological age, enhances our understanding of autism-specific sensory anomalies. Additionally, the fact that children with mTBI show balance anomalies up to 3 months post-injury, even when they are no longer highly symptomatic may be related to altered processing of dynamic visual information and could have implications for the clinical management of mTBI patients, since symptoms resolution is commonly used as a criterion for return to activities. Finally, results stemming from populations with atypical development (autism) and with so-called transient neurological insult (mild TBI) not only contribute to enhance our understanding of sensorimotor integration mechanisms underlying postural control, but could also consist of sensitive and specific markers of dysfunction in these populations. Keywords : posture, balance, vision, sensorimotor development/ aging, autism, symptomatic mTBI, virtual reality.

Adenosine Triphosphate (ATP) can be released as a signal between cells in an autocrine and paracrine manner that binds purinergic receptors. Highly conserved, purinergic receptors expressed on the cell surface of neurons and astrocytes are capable of being activated across eight orders of magnitude from hundreds of nanomolar ATP to millimolar. Genetically encoded fluorescent protein biosensors have been used to detect ATP outside the cell, but a high affinity extracellular ATP sensor is required to study the ATP signaling dynamics from nanomolar to micromolar magnitudes. Previously, our lab developed a first generation sensor of extracellular ATP called ECATS1 (Conley et al.). To develop an improved sensor, we caried out site-directed mutagenesis of the sensor's ATP binding site and identified a mutant that exhibited a 4-fold increase in ATP binding affinity in solution. We then optimized the membrane-tethering of the sensor to achieve the 4-fold increase in extracellular ATP binding affinity when measured on live cell.s This second-generation sensor was dubbed ECATS2. As a proof-of-concept application, we sought to detect ATP release from cells using <i>in vitro</i> models of edema. We subjected HEK293A cells to hypo-osmotic shock (HOS), revealing ATP release at micromolar levels. Then we tested HOS in cultured cortical astrocytes, also revealing micromolar ATP release. However, when we tested neuron-astrocyte co-cultures, we no longer observed ATP release in response to HOS. Interestingly, this implies that co-culture either entirely prevented ATP release from astrocytes or dampened it into the nanomolar range below the limit of ECATS2 detection. Thus, we have validated the development of a higher affinity, second-generation sensor and used it to discover that ATP release from astrocytes after HOS can be affected by the presence of neurons. <br>