Traumatic brain injury (TBI) is a serious health concern, causing cognitive, motor, and sensory deficits, including olfactory dysfunction. This dissertation explores the effects of TBI on synaptic plasticity within the olfactory system, seeking to define mechanisms guiding postinjury sensory reinnervation. Physical forces induced by TBI can axotomize olfactory receptor neurons (ORNs), which innervate olfactory bulb (OB). These axons regenerate OB projections after injury, a process involving growth through a complex extracellular matrix (ECM). As such, we investigated a potential molecular mechanism capable of modifying local OB ECM to support postinjury synaptogenesis. Since matrix metalloproteinases (MMPs) and their ECM substrates are recognized for TBI therapeutic potential, we explored the role of MMP9 and its substrate osteopontin (OPN) in promoting ORN reinnervation of the OB after mild fluid percussion injury (FPI). First, we confirmed that FPI deafferented the mouse OB. In Chapter 2, we showed concurrent activation of neuroglia, elevated spectrin proteolysis and reduction in ORN-specific olfactory marker protein (OMP). As OMP normalized during regeneration, growth associated protein-43kD (GAP-43) peaked, marking OB entry of ORN growth cones. Ultrastructural analysis revealed ongoing ORN axon shrinkage and degeneration, glial phagocytosis of cellular debris, and a reorganization of synaptic structure. To explore ECM role in mediating postinjury OB reinnervation, we defined the time course of MMP9 activity and several downstream targets. Chapter 3 reports biphasic MMP9 activity increase during acute/subacute degeneration, accompanied by robust generation of 48kD OPN cell signaling peptide. OPN receptor CD44 also increased during the acute/subacute interval, suggesting potential interaction of the two proteins. Finally, we utilized MMP9 knockout (MMP9KO) mice to confirm MMP9 role in OB synaptogenesis. In Chapter 4, MMP9KO reversed FPI-induced lysis of 49kD OPN and altered postinjury expression of ORN axon degeneration marker OMP. Additional ultrastructural analysis verified delayed recovery of OB synaptic features within the injured MMP9KO. Overall, we demonstrated that mild FPI elicits ORN axotomy to induce OB reactive synaptogenesis, and that MMP9 supports reinnervation by processing OPN for activation of local glia, cells which reorganize the ECM for synapse regeneration.

It is estimated that there are 12.5 million people in England living with neurological disorders (Neurological Alliance, 2014). People with neurological disorders as a result of acquired brain injury (ABI) are living with short and long-term disabilities. These include cognitive impairment, and physical and emotional distress. One of the most common complaints by individuals who have ABI is attention impairment. Attention difficulties can have serious ramifications for daily functioning. Although studies have explored the effects of evidence-based interventions such as mindfulness-based therapy on attention abilities, and have found that it improves individuals' attention skills (Moore et al, 2012), thus far research has been conducted mainly with non-clinical populations. This study set out to investigate whether a mindfulness-based intervention could prove beneficial for people with neurological disorders, particularly whether it could positively impact on attention impairment. The study employed a one group pre-test post-test design. The intervention was adapted from the MBSR programme developed by Kabat-Zinn. Twenty-two participants with ABI were recruited. The Conners Continuous Performance Test 3rd Edition (CPT-3), Mindful Attention Awareness Scale (MAAS), Attention Process Training-II Attention Questionnaire (APT-II AQ) and Clinical Outcome in Routine Evaluation-Outcome Measure (CORE-OM) were utilised to measure outcomes. The results revealed that there was a clinical improvement in self reported measures of mindfulness (MAAS) (Cohen d=0.28), attention (APT-II AQ) (Cohen d=0.33), and psychological distress (CORE-OM) (Cohen d=0.72). This was not observed using the neuropsychological test of attention (CPT-3) for overall group scores, but further evaluation showed some individuals' scores improved. The study is promising as it indicates that mindfulness based treatment can be effective with attentional problems as well as in reducing psychological distress for individuals with ABI. This could be valuable in terms of providing treatment for this client group and adds to the expanding research base on mindfulness-based intervention with this population.

Recently, the literature concerned with the possibilities and limitations of working memory training has been growing rapidly. Nonetheless, there are still no clear answers about the principles of its effectiveness or transfer effect. The main questions we ask are about effectiveness of cognitive training in patients after stroke or TBI. To our knowledge this group hasn't been studied in this context yet. To do this, we compare two types of cognitive training - extensively studied N-back training (n=11) and still more popular group cognitive therapy (n=9) with a placebo control group (n=5) who recieves "training" in a simple computer game. The placebo control group then continues in N-back training. Our hypothesis is that after 3 weeks the two trainings should lead to significantly higher gains in cognitive tests scores than the placebo condition. Also, we expected N-back to be more effective than group cognitive training in domains more closely related to executive control. We tested attention, fluid intelligence, short-term and working memory. We also recorded participants well-being. Following training, there were no significant differences between N-back and group training. N-back group scored significantly higer on Trail Making Test A than control group (p=0,026). Although our study doesn't...

National concern over traumatic brain injury (TBI) is growing rapidly. Recent focus is on mild TBI (mTBI), which is the most prevalent injury level in both civilian and military demographics. A preeminent sequelae of mTBI is cognitive network disruption. Advanced neuroimaging of mTBI victims supports this premise, revealing alterations in activation and structure-function of excitatory and inhibitory neuronal systems, which are essential for network processing. However, clinical neuroimaging cannot resolve the cellular and molecular substrates underlying such changes. Therefore, to understand the full scope of mTBI-induced alterations it is necessary to study cortical networks on the microscopic level, where neurons form local networks that are the fundamental computational modules supporting cognition. Recently, in a well-controlled animal model of mTBI, we demonstrated in the excitatory pyramidal neuron system, isolated diffuse axonal injury (DAI), in concert with electrophysiological abnormalities in nearby intact (non-DAI) neurons. These findings were consistent with altered axon initial segment (AIS) intrinsic activity functionally associated with structural plasticity, and/or disturbances in extrinsic systems related to parvalbumin (PV)-expressing interneurons that form GABAergic synapses along the pyramidal neuron perisomatic/AIS domains. The AIS and perisomatic GABAergic synapses are domains critical for regulating neuronal activity and E-I balance. In this dissertation, we focus on the neocortical excitatory pyramidal neuron/inhibitory PV+ interneuron local network following mTBI. Our central hypothesis is that mTBI disrupts neuronal network structure and function causing imbalance of excitatory and inhibitory systems. To address this hypothesis we exploited transgenic and cre/lox mouse models of mTBI, employing approaches that couple state-of-the-art bioimaging with electrophysiology to determine the structural- functional alterations of excitatory and inhibitory systems in the neocortex.

Deficits in executive function are commonly reported following Traumatic Brain Injury (TBI) and are important for establishing functional impairments. Understanding the nature of executive dysfunction following TBI is often complicated by secondary factors that can impact measured ability. This study sought to clarify the persistent effects of TBI on executive function, as measured by the Wisconsin Card Sorting Test (WCST), while accounting for effort given during testing, as measured by the Portland Digit Recognition Test. Results suggested a dose-response relationship between TBI severity and subsequent WCST deficits. Mild TBI patients who provided good effort during testing showed no observable differences from locally matched controls on WCST performance. Effort during testing was found to have a larger overall effect on WCST performance than moderate-to-severe TBI or dementia. The present study highlights the need to account for secondary factors, such as effort during testing, to accurately measure cognitive dysfunction following compensable injuries.

A significant subset of mild traumatic brain injury (mild TBI) and chronic pain (CP) patients report, and sometimes show objective evidence of, persisting cognitive problems. Despite differences in injury mechanisms, there is considerable overlap in the types of persisting cognitive symptoms that are reported by the two populations. Psychogenic, rather than physiogenic, factors are thought to play an important role in the maintenance of these persisting symptoms. The current investigation examined the contributions somatization, depression, and anxiety had on an objective measure of “working attention.” In order to best elucidate the influences these psychological factors had on attentional performance, only individuals who passed well-validated and popular indicators of cognitive and self-report validity were included in the study. Two hundred and forty-nine individuals (n = 116 TBI; n = 133 CP) met the inclusionary criteria for the study. Psychological factors were assessed using Scales 1 (Hypochondriasis), 2 (Depression), 3 (Hysteria), and 7 (Psychasthenia) of the Minnesota Multiphasic Personality Inventory-II. “Working attention” was measured using the demographically-adjusted T-scores for the Working Memory and Processing Speed Indexes of the Wechsler Adult Intelligence Scale- 3. Results indicated that a high rate of psychological complications was observed in the mild TBI and CP groups but not the moderate-severe traumatic brain injury (M/S TBI) comparison group. Analysis indicated that psychological elevations were not significantly related to spontaneously-reported symptoms or working attention deficits for the mild TBI group but were for the CP and M/S TBI groups. The current results are important for understanding the psychological complications that may occur in individuals exhibiting persisting cognitive problems in these clinical populations.

Objective: Children and adolescents with a history of traumatic brain injury (TBI) are at increased risk for developing social incompetence and impairment in broad psychosocial functioning. The aim of this study was to examine the relationship between history of TBI, social competence, and broad psychosocial functioning using meta-analytic methods. Methods: Studies relating to social outcome following pediatric TBI were searched for using scientific, academic databases. Sixteen studies (N=2,005) met inclusion criteria, and relevant data relating to social functioning was extracted. Meta-analytic methods were used in order to obtain Hedges's g effect size data for mild, moderate, and severe TBI groups. Meta-regressions were also used to examine the effect of potential moderating variables, including Glasgow Coma Scale (GCS), socioeconomic status (SES), gender, control group (typically developing (TD) or orthopedic injury (OI)), and time/age related variables. Finally, publication bias was calculated using funnel plots and Rosenthal's fail-safe N. Results: A dose-response effect was observed with mild (Hedges's g = -0.387), and moderate (Hedges's g = -0.459) groups demonstrating smaller effects when compared to the severe group (-0.814) on measures of broad psychosocial function. A dose-response effect was also observed on measures of social competence, with mild (Hedges's g = -0.098) and moderate (Hedges's g = -0.450) TBI groups demonstrating smaller effect sizes when compared to the severe TBI group (Hedges's g = -0.832). The GCS was a significant predictor of both broad psychosocial functioning (B = 0.065, p < 0.001) and social competence (B = 0.079, p < 0.001), such that more severe injuries predicted poorer social outcomes. Gender was a significant predictor of effect size (B = 0.018, p = 0.05), such that higher proportions of females was associated with smaller effect sizes. Finally, the type of control group used in these studies was also a significant predictor of effect size (B = 0.369, p = 0.03), such that studies that used TD produced larger effect sizes when compared to studies that used OI. Overall, there was little evidence for publication bias. Conclusions: Children and adolescents with a history of TBI demonstrated significant differences from their peers in social competence and broad psychosocial functioning following TBI. The severity of the injury is important in understanding and predicting social outcomes following pediatric TBI. Implications of these findings are discussed.

The incidence of mild blast traumatic brain injuryhas risen due tothe increased use of improvised explosive devices (IEDs) in militaryconflicts. Mild blast TBI (mbTBI) is especially relevant due to its lack of acutely observable symptoms, and to its association with long-term neurodegenerative and neuropsychiatric disorders. Predominantly, TBI patients often suffer from chronic stress, neuropathic pain and headaches, which greatly compromise the health and quality of life of these individuals. Treatments for neuropathic pain have been empirically found and produce little effect in lessening neuropathic pain, likely due to the lack of targeted therapies. This highlights the need for better understanding of the molecular mechanisms underlying neuropathicpain, TBI and chronic stress that could lead to mechanistic therapeutic targets. Oxidative stress is an important mechanism of the pathophysiology of neuropathic pain, TBI and chronic stress. We hypothesize that acrolein, an endogenously formed neurotoxin, is able to stay active in the body for up to 10 days, is involved in the pathophysiology of neuropathic pain in TBI and chronic stress. This study aims to correlate acrolein elevation in the body with neuropathic pain, deepen the understanding of underlying mechanisms of pain in TBI and chronic stress, and mitigate this pain with acrolein scavenging. The ultimate goal of this research is to provide therapies for TBI and chronic stress patients that can eliminate pain and significantly improve their healthand quality of life

Thesis advisor: Belle Liang / Traumatic brain injury (TBI) survivors often experience isolation from their primary support network following their injury (Marsh, Kersel, Havill, & Sleigh, 1998). Computer-mediated support groups (CMSGs) offer a virtual platform for individuals with complex medical concerns to exchange emotional and informational support (Braithwaite, Waldron, & Finn, 1999). To date, no research has examined the use of CMSGs, such as TBI-related Facebook support groups, for TBI survivors. There is also limited research investigating how emotional and informational support provided and received (i.e., supportive exchanges) relate to well-being and online relational health (Liang et al., 2002). This study examined the relationship between four supportive exchanges and well-being and relational health for TBI survivors using TBI-related Facebook support groups, as well as whether a gender norm—emotional control—and network preference moderated these relationships. Participants included 191 TBI survivors recruited across 14 TBI-related Facebook support groups. Multiple regression analyses tested whether four supportive exchanges directly predicted well-being and relational health after controlling for age and extraversion. Results revealed that supportive exchanges did not predict well-being. However, emotional support provided, emotional support received, and informational support received all predicted higher levels of online relational health. Informational support provided predicted lower levels of online relational health. Additional multiple regression analyses tested whether emotional control and four aspects of network preference moderated the relationship between supportive exchanges and well-being and relational health. Although higher levels of emotional control directly predicted lower levels of relational health, and a preference for weak-tie support networks (e.g., online acquaintances) predicted lower levels of well-being, the moderating effects were generally not significant. The findings underscore the importance of supportive exchanges in developing online relational health for TBI survivors using Facebook support groups. It also suggests that this relationship was not dependent on emotional control and network preference. Future research should investigate other factors affecting supportive online communication for TBI survivors and when they may benefit most from online support. / Thesis (PhD) — Boston College, 2018. / Submitted to: Boston College. Lynch School of Education. / Discipline: Counseling, Developmental and Educational Psychology.

Syfte:Syftet med litteraturstudien var att undersöka hur en smartphone kan användas inom rehabilitering efter FHS, i vilken utsträckning smartphonen används. Vilka effekter smartphonen kan ge på i det dagliga livet samt betydelsen en smartphone kan utgöra. Metod:För att besvara syftet så utfördes en litteraturstudie som innefattar kvalitativ och kvantitativ forskning baserad på åtta studier.  Resultat:Smartphonen har många fördelar som ett kompensatoriskt hjälpmedel samt är betydelsefull för personerna i det dagliga livet på många sätt. Signifikanta effekter kunde uppmätas som ledde till att fler aktiviteter både påbörjas och avslutades i rätt tid, därmed så hanteras många av grundproblemen med förvärvad hjärnskada (FHS), såsom svårigheter med minne, planering, initiering och organisering. Smartphonen föredrogs också av användarna framför andra hjälpmedel.  Slutsats:Studien visar att de finns stora fördelar med att implementera smartphonen som en del av rehabiliteringen av förvärvad hjärnskada. Vidare visar studien att smartphonen är den del av människors liv oavsett med eller utan FHS.  Det finns behov av vidare forskning inom ämnet då det finns få studier som belyser smartphonens som kompensatoriskt hjälpmedel i dagsläget. / Aim: The aim of this literature study was to describe how the smartphone is used as a compensatory aid in rehabilitation and the importance it can have for people with acquired brain injury. Method: To answer the purpose, a literature study was carried out which included qualitative and quantitative research based on eight studies. Result: The smartphone has many advantages as a compensatory aid and it shows important for people with acquired brain injury in their daily life in many ways. Significant effects could be measured which led to more activities being initiated and completed at the right time, thus many of the basic problems with acquired brain injury are addressed, such as problems with memory, planning, initiation and organization. The smartphone was also preferred by the users in front of other devices. Conclusion: The study shows great advantages in implementing the smartphone as part of the rehabilitation of acquired brain injury. Furthermore, the study shows that the smartphone is the part of people's lives regardless of if they suffer from acquired brain damage or not. There is a need for further research within the subject since there are few studies that shed light on smartphone's as compensatory aid at present.