Traumatic Brain Injury (TBI) is linked to a diverse range of diffuse pathological damage for which there is a severe lack of therapeutic options. A major limitation to drug development is the inability to identify causal mechanisms that link head trauma to the multitude of secondary injury cascades that underlie neuropathology. To elucidate these relationships, it is important to consider how physical forces are transmitted through the brain across multiple spatial scales ranging from the whole head to the sub-cellular level. In doing so, the mechanical behavior of the brain is typically characterized solely by its material properties and biological structure. Alternatively, forces transmitted through distinct cellular and extracellular structures have been shown to influence physiological processes in multiple cell types through the transduction of mechanical forces into cellular chemical responses. As an essential component of various biological processes, these mechanotransduction events are regulated by mechanical cues directed through extracellular matrix (ECM) and cell adhesion molecules (CAM) to mechanosensitive intra-cellular structures such as focal adhesions (FAs). Using a series of in vitro models, we have implicated FAs in the cellular mechanism of traumatic axonal injury by showing that forces directed through these structures potentiate injury levels and, moreover, that inhibition of FA-mediated signaling pathways may be neuroprotective. In addition, we show that localizing trauma forces through specific brain ECM results in differential injury rates, further implicating mechanosensitive cell-ECM linkages in the mechanism of TBI. Therefore, we show that FAs play a major role in axonal injury at low strain magnitudes indicating that cellular mechanotransduction may be an important mechanism underlying the initiation of cell and sub-cellular injuries ultimately responsible for the diffuse pathological damage and clinical symptoms observed in diffuse axonal injury. Furthermore, since these mechanisms may present the earliest events in the complex sequelae associated with TBI, they also represent potential therapeutic opportunities. / Engineering and Applied Sciences

Objectives: The majority of individuals who sustain a mild traumatic brain injury (mTBI) will experience a full recovery within the first weeks or months post-injury. However, some individuals will experience ongoing difficulties, or persistent post-concussion symptoms (PCS), for years following the injury. To date, most researchers have attributed PCS to either neuropathological factors or to psychogenic factors. Lacking exploration has been the role of psychosocial variables and the consideration of PCS from a more holistic, or 'whole person', perspective. As such, the goal of the current study was to undertake an investigation of persistent PCS using a broad, neuropsychosocial framework. Specifically, this was done by investigating how (a) cognitive functioning, (b) susceptibility to anxiety while in the context of a stressful situation (i.e., anxiety susceptibility), and (c) multiple components of identity (including self-perception, TBI- related self-concept, and TBI-related social identity) influence the severity of persistent PCS. The main underlying assertion to this research is that there are multiple factors that underlie the experience of persistent PCS; a purely neuropathological or psychogenic perspective is not sufficient to understand the complex processes inherent in recovery after mTBI. Method: The sample consisted of 21 adults, between 20 and 65 years of age, who had sustained an mTBI at least one year earlier. Following a telephone interview to determine eligibility (and a separate telephone interview with a source of collateral information) the participants completed a number of standardized neuropsychological measures and self- report questionnaires during an in-person, one-on-one data collection session. Results: The only injury-related or demographic variable that had an influence on PCS was injury etiology, whereby individuals with sports related injuries reported significantly less PCS than did those who sustained non-sports related injuries (e.g., motor vehicle accidents). Cognitive functioning had no influence on PCS severity, nor did anxiety susceptibility. However, one's general propensity to experience anxiety (i.e., trait anxiety) was a significant predictor of PCS. Further, multiple aspects of identity influenced PCS with both current self-perception and TBI-related social identity being significant predictors of self-reported PCS severity. Conclusions: Despite the failure to find any impact of neuropsychological factors on PCS in the current study, other lines of research have demonstrated neuropathological changes associated with mTBI – some of which may be chronic. Therefore, cognitive functioning may not be a sufficiently sensitive indicator of possible neuropathology at more than one year post-injury. On the other hand, the current study demonstrates that psychological and psychosocial factors are highly relevant to recovery and outcome following mTBI, and are significant predictors of PCS severity. Overall, the results support the assertion that recovery after mTBI is complex and that there are multiple factors that underlie persistent PCS. Further, the study demonstrates the importance of conceptualizing the process of recovery from a broad, neuropsychosocial perspective. Implications for treatment interventions and future research are discussed. / Graduate

The long-term consequences of repetitive mild traumatic brain injuries (mTBIs), or concussions, as well as the immediate acute dangers of head collisions in sport have become of growing concern in the field of medicine, research and athletics. An estimated 3.8 million sports-related concussions occur in the United States annually, with the highest incidence having been documented in football, hockey, soccer, basketball and rugby (Harmon et al., 2013). The incidence of concussion in the National Rugby League (NRL) corresponds to approximately 8.0-17.5 injuries per 1000 playing hours, with tackling having been identified as the most common cause (Gardner et al., 2014; King et al., 2014). The highest incidence of rugby concussive impacts is a result of shoulder-to-head collisions (35%) during tackles and game play (Gardner et al., 2014). Shoulder-to-head concussive events occur primarily on the ball carrier and secondarily on the tacklers (Hendricks et al., 2014; Quarrie & Hopkins, 2008). While some studies report that the ball carrier is at a greater risk of sustaining a concussion (Gardner et al., 2015; King et al., 2010, 2014), others have demonstrated a greater incidence of tacklers being removed from play for sideline concussion evaluation (Gardner et al., 2014). Given this discrepancy, the purpose of this study was to compare dynamic response and brain tissue deformation metrics for ball carriers and defensive tacklers in professional rugby during shoulder-to-head concussive impacts using in-laboratory reconstructions. Ten cases with an injured defensive tackler and ten cases with an injured ball carrier were reconstructed using a pneumatic linear impactor striking a 50th percentile Hybrid III headform to calculate dynamic response and maximum principal strain values. There was no significant difference between the two impact conditions for peak resultant linear and rotational accelerations, as well as brain tissue deformation. Differences between metrics in this research and past research where the impacting system was not reported were discussed. These differences reflect the importance of accounting for impact compliance when describing the risk associated with collisions in professional rugby.

Severe traumatic brain injury (sTBI) is a cause of death and disability worldwide and requires treatment at specialized neuro-intensive care units (NICU) with a multimodal monitoring approach. The CT scan imaging supports the monitoring and diagnostics. The level of S100B and neuron specific enolase (NSE) reflects the severity of the injury. The therapy resistant intracranial hypertension requires decompressive craniectomy (DC). After DC, the cranium must be reconstructed to recreate the normal intracranial physiology as well as to address cosmetic issues. The evolution of the pathological intracranial changes was analyzed in accordance with the three CT classifications: Marshall, Rotterdam and Morris-Marshall. The Rotterdam scale was best in describing the dynamics of the pathological evolution. Both the Rotterdam score and Morris- Marshall classification showed strong correlation with the clinical outcome, a finding that suggests that they could be used for prognostication. We demonstrated a clear correlation between the CT classifications and concentrations of S100B and NSE. The results revealed a concomitant correlation between NSE and S100B and clinical outcome. We found that the interaction between the ICP, Rotterdam CT classification, and concentrations of biochemical biomarkers are all associated with DC. We found a high percentage of complications following cranioplasty. Our results call into question whether custom-made allograft should be considered the best material for cranioplasty. It is concluded that both the Rotterdam and Morris-Marshall classification contribute to clinical evaluation of intracranial dynamics after sTBI, and might be used in combination with biochemical biomarkers for better assessment. The decision to perform DC should include a re-assesment of ICP evolution, CT scan images and concentration of the biochemical biomarkers. Furthermore, when determining whether DC treatment should be used, surgeon should also consider the risks of the following cranioplasty.

Neuropsychological rehabilitation following acquired brain injury is increasingly recognized as essential with the advancements in research evidence of its effectiveness, particularly as current estimates of disability following the most common forms of brain injury (traumatic brain injury and cerebrovascular accident) are so high. Improvements in predictive capabilities of researchers and clinicians are paramount in designing effective interventions. As many variables associated with outcome following brain injury are not controllable (e.g. severity of the injury, age, education), it is essential that rehabilitation programs design interventions to target those variables that are susceptible to amelioration. While personality factors have been shown to affect outcome in other medical illnesses, only a few studies have examined the influence of personality on outcome following neurorehabilitation for acquired brain injury. The results of these studies have been mixed. This study used the Millon Behavioral Medicine Diagnostic (MBMD) to predict outcome as measured by the Mayo-Portland Adaptability Index (MPAI-4) following brain injury rehabilitation in a heterogeneous sample of persons with acquired brain injuries (N = 50). It was hypothesized that specific coping styles scales from the MBMD (Introversive, Dejected, Oppositional), which are based on Millon's personality system, would predict outcome. Results indicated that both the Introversive and Oppositional coping styles scales accounted for significant amounts of variance in outcome beyond that accounted for by the severity of the injury alone (p < .001). In both cases, individuals with mild/moderate-moderate/severe limitations following completion of the rehabilitation program had significantly higher scores on the Introversive and Oppositional coping compared to individuals with more successful outcomes. The hypothesis that a dejected coping style would predict outcome was not supported. Implications for rehabilitation are discussed in the context of Millon's personality system.

Magister Scientiae (Occupational Therapy) - MSc(OT) / Traumatic brain injury (TBI) is a major public health concern which mostly affects the economically viable population. In addition, the Code of Good Practice as described in South African Labour Law serves as a guide for employers to encourage equal and fair opportunities for employees with disabilities. However, despite the presence of this policy, as well as other legislation, research has shown that individuals with TBI are failing to return to work. The Model of Occupational Self-Efficacy (MoOSE) was developed as a client centered approach to return individuals with TBI to work. The aim of the current study was to explore, and describe the experiences and perceptions of occupational therapists who have used the MoOSE in the vocational rehabilitation and return to work process of clients with TBI. The participants in the study were selected by means of purposive sampling and semi-structured face-to-face interviews were conducted on a monthly basis for three months with 10 occupational therapists. The semi-structured interviews were used to gain insight into and explore the perceptions of the occupational therapists who have used the MoOSE in their vocational rehabilitation programmes with clients who have suffered TBI. The findings of the study were analyzed by means of thematic content analysis. The outcome of this study was aimed at finding ways to enhance / improve the model when it is used in the vocational rehabilitation process with people who have suffered TBI. Informed consent was obtained from the research participants and confidentiality of their information was maintained. Data was collected by means of semi-structured interviews which were audiotaped and transcribed. Transcriptions were analysed by using constant comparative methods of data analysis which resulted in categories, which reflected the purpose of the study being created. The analysis of transcripts was done using Microsoft Word. Results were then divided into themes and discussed holistically. Four themes emerged that answered the research question. Theme one described how client related factors impacted on the implementation of the MoOSE. Theme two explored the therapist related factors that impacted on the implementation of the MoOSE while theme three discussed how characteristic of the model impacted on the vocational rehabilitation and return to work process. The participants appreciated the clear four stages of the MoOSE and the dynamicity of the model. Theme four described how the job market and employer perceptions impacted on the return to work process. Recommendations were then discussed that could further improve the model and the implementation thereof. Recommendations included adding a motivation component to the MoOSE, involving family members in the rehabilitation process and therapist reflection as a means to foster client-centered practice. Other recommendations were aimed at addressing policy issues which interferes with the return to work process and encouraging interdisciplinary collaboration in the vocational rehabilitation of individuals with TBI.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2017-07-25T12:32:10Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Angelo-tese doutorado.pdf: 2038180 bytes, checksum: be401d99f221bbdf4a8d892feb579538 (MD5) / Made available in DSpace on 2017-07-25T12:32:10Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Angelo-tese doutorado.pdf: 2038180 bytes, checksum: be401d99f221bbdf4a8d892feb579538 (MD5) Previous issue date: 2016-11-24 / Introdução: A incidência de hidrocefalia pós craniectomia descompressiva(CD) em pacientes com traumatismo cranioencefálico(TCE) é entre 0-45% segundo a literatura. A hidrocefalia traz prejuízos ao prognóstico neurológico e demanda reconhecimento clínico precoce. Existem diversas variáveis radiológicas e clínicas descritas com associação ao risco de hidrocefalia. Para estudar a influência desses fatores conduzimos um estudo retrospectivo, observacional em um centro terciário de atendimento a pacientes com TCE com foco principal na análise do volume de herniação transcraniana (VHTC) após CD. Métodos: selecionamos 50 pacientes que realizaram CD para TCE entre janeiro de 2014 e janeiro de 2015. Hidrocefalia foi reconhecida e definida na presença de critérios radiológicos de Gudeman, indicação de derivação ventricular, e na mensuração do Índice de Evans modificado maior que 33%. Analisamos as seguintes variáveis: Idade, Sexo, Escala de Coma de Glasgow à admissão, reatividade pupilar, índice de Zunkeller, presença de higroma, VHCE, diâmetro da craniectomia e distância da craniectomia em relação à linha média. Regressão logística foi utilizada definindo o desfecho com ou sem hidrocefalia como medida de análise. Resultados: 17 pacientes desenvolveram hidrocefalia (34%). VHCE após CD (p<0.001), Higroma subdural (p<0.001) ), Escala de coma de Glasgow abaixo de 6( p=0.015), sinais de herniação uncal(p=0.042) e maior valor no índice de Zumkeller(p=0.04) foram associados com o desenvolvimento de hidrocefalia pós-CD. Regressão logística demonstrou que entre essas variáveis as que foram consideradas como fatores de risco independente são o VHTC (OR 11.08; 95%IC 2.10,58.4; p=0.004) e a presença de higroma (OR 49.59; 95%IC 4.1,459;p=0.002). Conclusões: Observamos uma forte associação entre a severidade do TCE, o volume de herniação cerebral transcraniana e presença de higroma subdural com o desenvolvimento de hidrocefalia. Pacientes com esses achados devem ser acompanhados rigorosamente visando evitar prejuízo clínico. / In patients undergoing decompressive craniectomy(DC) for traumatic brain injury(TBI) there has been reported an incidence of hydrocephalus between 0-45%. Hydrocephalus affects long term survival and needs a prompt and correct diagnosis. There are several radiological and clinical features described in association with development of hydrocephalus. For study the influence of these factors we conducted a retrospective observational single-center cohort study in a tertiary care center with special attention to the transcalvarial brain herniation volume(TCH) after DC. Methods: We selected 50 patients that underwent DC after closed head injury between january 2014 and January 2015. Hydrocephalus was defined as a modified frontal horn index greater than 33%, Gudeman CT scan criteria or insertion of ventriculoperitoneal Shunt. Variables we analyzed were: age, post-resuscitation Glasgow Coma Scale (GCS) score, pupil reactivity, Zunkeller index, presence of hygroma, TCH volume, craniectomy diameter and distance of craniectomy from midline. Logistic regression was used with hydrocephalus as the primary outcome measure. Results: 17 patients developed hydrocephalus(34%). TCH volume after decompression ( p<0.001), subdural hygroma ( p ), lower admission Glasgow Coma Scale score ( p=0.015), unilateral pupil reactivity(p=0.042) and higher Zumkeller index(p=0.044) were significant risk factors for hydrocephalus after decompressive craniectomy. Logistic regression analysis showed that factors independently associated with the development of hydrocephalus was the TCH volume (odds ratio 11.08; 95%CI 2.10, 58.4; p = 0.0046), and presence of hygroma (odds ratio 49.59; 95%IC 4.1, 459; p=0.002). Conclusions: There is a clear association between severity of TBI, TCH volume and subdural hygroma with the development of hydrocephalus. Clinicians should follow closely patients with those findings in order to avoid late deterioration.

Motion capture technology and Magnetic Resonance Imaging with Diffusion Tensor Imaging (MRI-DTI) were used in this work to detect subtle abnormalities in patients with mild traumatic brain injury (MTBI). A new concept, termed dynamic variability, is introduced in this work to quantify and localize gait variability. Three chronic MTBI patients were recruited from the Veterans Affair Medical Center in Iowa City, IA, and three healthy controls with height, weight, and gender matched to the patients were recruited from the Reserve Officers' Training Corps in Iowa City, IA. Kinematic and kinetic data of the subjects were collected during the performance of three gait testing scenarios. The first test involved single-task walking and was used as a baseline. The second and third tests were dual tasks that involved walking while performing a cognitive or motor task and were designed to magnify gait abnormalities. The results showed that MTBI patients had reduced gait velocity, shortened stride length, and larger step width; findings that are consistent with those published in the literature. The new dynamic variability factor found that, as compared to controls, MTBI patients had more variability in their hip and ankle joint moments. MRI-DTI has been used to detect dysfunction of the major white matter tracts in chronic MTBI patients; although, the sample size of this study was too small to detect a difference between the MTBI and control subjects. The imaging and gait abnormalities are suggestive of frontal lobe-white matter tracts dysfunction.

No description available.

Conversation is a highly interactive and coordinated effort between interactants. For example, interactants often mimic the behaviors and speech of one another and coordinate the timing of behaviors, or interactional synchrony. Despite being affected in certain neurological and psychiatric disorders, the neural mechanisms underlying these processes are not understood. The goal of this study is to understand the role of the ventromedial prefrontal cortex (vmPFC), an area of the brain involved in social and emotional behavior, for interpersonal coordination, including mimicry and interactional synchrony. To test the role of the vmPFC for mimicry, normal comparison (NC), brain damaged comparison (BDC), and participants with vmPFC damage interacted in two sessions with a research assistant (RA) who was performing a target behavior (1st session: nodding, 2nd session: face touching). The amount of time the participants spent nodding or touching their face in each session was recorded. NC and BDC participants tended to mimic the partner and nodded slightly more in the session in which the RA was nodding, and touched their face slightly more in the session in which the RA was touching their face. In contrast, vmPFC patients showed no difference in their behaviors in either session, suggesting that they were not influenced by the partner's behaviors and did not mimic them. In a second experiment, all of the above participant groups had a naturalistic conversation with an unfamiliar interactional partner. The conversational data were analyzed for numerous aspects of interpersonal coordination, including convergence of number of words, words per turn and backchannels, reciprocity of self-disclosures, the use of questions, interactional synchrony, and a time series analysis of response latency and speech rate. The vmPFC participants performed consistently worse than NC participants on convergence of words and words per turn, self-disclosures and asking questions. All brain-damaged participants were impaired on aspects of interactional synchrony, and no conclusive results were found for the time series analysis of response latency and speech rate. This study provides support for the hypothesis that the vmPFC is important for interpersonal coordination as the vmPFC group differed significantly from the NC group on the majority of the analyses. The final goal of this study was to understand the effects of traumatic brain injury (TBI) on interpersonal coordination. TBI patients participated in all of the experiments described above and preliminary results showed that they also seemed to be impaired on the mimicry task, and they performed slightly worse than NC participants on many of the interpersonal coordination analyses of the conversational data. This suggests that TBI also does seem to affect certain aspects of interpersonal coordination.