<p>Research in the field of human injury biomechanics with respect to athletes has indicated that head acceleration events (HAEs) suffered during participation in a contact sport can cause long-term neurological changes that present asymptomatically. This concept has been referred to as “mild” traumatic brain injury (mTBI). This mirrors results found in soldiers, where it is also now thought that traumatic brain injury, coupled with psychological trauma can lead to posttraumatic stress disorder (PTSD). Current consensus amongst the neurotrauma research community is that all HAEs matter, whether caused by blast, blunt force, or directed energy weapons.</p> <p><br></p> <p>Previous research has focused on the long-term changes that have been demonstrated and quantified, however very little research has been done to quantify the effects of a single insult to the brain. Several studies have had participants perform head motions while in a magnetic resonance imaging (MRI) scanner. Digital twins may be used to simulate the effects of an insult, be it blast, blunt force, or directed energy to an object. Finite element models of the human head and brain have a long history of development from the earliest models in the 1970s to today. Currently, numerous software packages allow for the regularization and comparison of MRI datasets. Some software packages offer additionally the ability to create subject specific finite element meshes interactively from a single MRI image. Previous research in the HIRRT Lab reduced the time to generate simulation geometry to approximately 48 hours to generate a patient specific finite element mesh. This represented a substantial reduction in the processing time for a single scan, which to the knowledge of the authors required on the time scale of weeks to process a single geometry including the skull robustly or required costly software licenses, and still required user interactive processes. The architecture and deployment of the HIRRT Lab Cluster, a high-performance computing system that is a cost-optimized research tool to enable rapid processing of scans to simulation geometry using batch processes on a Slurm cluster. There are software optimizations, operating system optimizations, and Linux kernel-level optimization (and selections) utilized that enable the hardware selected to perform optimally. </p> <p><br></p> <p>To the knowledge of the author, no single pipeline enables the automated generation of robust, patient specific finite element meshes from raw datasets fresh from an MRI. This package addresses those limitations with a design heavily tilted towards Linux cluster implementations. The author has created a pipeline of code designed to run on a Linux-based compute cluster that is capable of processing 1700 scans from raw T1-weighted MRI scans to a finite element mesh with regions of interest (ROIs) identified as element sets, and white matter fiber orientation determined from diffusion tensor imaging (DTI) scans in under 7 days using the current hardware available in the HIRRT Lab Cluster with appropriate software licensing. This represents a speed up of over 1200x compared to the original program overall at just mesh processing, and a speed up of 22x for a single scan being processed, with additional features and detail not captured by the original code. </p> <p><br></p> <p>Accurate representative models for subpopulations via their immutable traits (e.g. size, biological sex, ethnicity/ancestry, or age) can further reduce the number of simulations that are required to accurately assist in the improvement of finite element models that may be used to improve the design of personal protective equipment, create new techniques, or aid in the design of new vehicles capable of reducing the exposure of individuals to potentially traumatic damage. The use of subpopulation groupings rather than the simulation of each unique individual, even models consisting of bounding cases, such as the largest or smallest representative members of a subpopulation can reduce the amount of data that needs to be processed to generate useful design feedback for engineers. </p> <p><br></p> <p>Subject-specific models allow for greater variation in strain due to geometric differences between individuals brains and should be used where possible to describe a given individual’s strain history more accurately, which can be used to assess the formation of damage as indicated by biomarkers. To understand the long-term effects of blast overpressures on brain structure, function, and chemistry, and subsequently develop appropriate mitigation strategies, computational models of individual soldiers must be developed. These models must integrate blast physics and neuroimaging of actual tissue damage to the brain. There is a need to develop constitutive equations capable of being used in multi-scale models to relate various insults directly to damage in the brain. These equations should be linked to damage as indicated through various MRI scan types and used to robustly assess individuals over the course of their unique impact histories. Through the development of a digital twin in this manner, unique predictive medicine may be used to proactively identify those athletes and warfighters who may be at higher risk for long term detrimental effects from further exposure to HAEs.</p>

Yes / Background: Depression is a common psychiatric problem following traumatic brain injury (TBI) with reported prevalence rates of 30-77% in the first year post-TBI. Given the negative influence of post-TBI depression on cognition, interpersonal, social, physical and occupational functioning; early initiation of pharmacotherapy to prevent post-TBI depression has been considered. This systematic review will synthesize the available evidence from published studies on the effectiveness and harms of pharmacotherapy for the secondary prevention of post-TBI depression. Method: Studies published before November 2017 were reviewed. Six databases were searched, with additional searching of key additional documents. Studies meeting inclusion criteria were evaluated for methodological quality. Results: Six articles addressing five studies met inclusion criteria. Study designs included three randomised controlled trials (RCT), two retrospective cohorts and one case-control. Prophylactic pharmacotherapy included antidepressants, beta-blockers and statins. In one RCT, the number-needed-to-treat with sertraline to prevent one case of depression post-TBI at 24 weeks was 5.9 (95%CI: 3.1-71.1). Prescribing beta-blockers prior to TBI reduced the depression risk regardless of the specific brain trauma. TBI patients with pre-existing hyperlipidemia not treated with statins had an increased depression risk compared to those without hyperlipidemia. Conclusion: Early initiation of sertraline prophylaxis in nondepressed TBI patients shows promise to reduce the odds of post-TBI depression developing. However, in the absence of rigorous study of tolerability, existing data are insufficient to recommend sertraline prophylaxis. Optimal timing and treatment duration with identification of patients most likely to benefit from prophylaxis require further consideration. Dedicated prospective studies assessing the effects of beta-blockers and statins on post-TBI depression are required. / The Transport Accident Commission (TAC), through the Institute for Safety, Compensation and Recovery Research (ISCRR) at Monash University, provided funding for this review.

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The purpose of this study was to evaluate the performance of adults with traumatic brain injury (TBI) on a spoken persuasive discourse task and to evaluate the affects of eliciting this language sample. Ten adults with TBI (mean age = 51 years and 5 months) and ten adults matched by age and gender completed two spoken language tasks. These tasks required them to verbally provide their opinion of whether trained animals in circuses should be allowed to perform for the public and also whether public transport should be encouraged for everyone to use. One of the tasks was provided with examples for and against the topic within the instructions whereas the other task instructions provided no examples. The presentation of these tasks was alternated within the groups so as not to assist with task practice. Language measures included productivity (total number of words, mean length of T-units, T-units per minute and percentage of T-units with mazes) and complexity (total number of clauses, clause density and clause type). Pragmatic measures included the essential features of argument as identified in the developmental literature (number of claims, reasons, elaborations, repetitions, irrelevancies, and presence of an introduction and conclusion). The TBI group out-performed their age-matched peers on language complexity measures of total number of clauses and independent clauses used, however used significantly more adverbial clauses. On comparison of the elicitation technique, the instructions with examples elicited a significantly greater number of reasons than that of the basic instructions. The results are discussed alongside current literature in the field of discourse production and persuasion. Implications for clinical practice and future directions for research in this area are also suggested.

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Objectives: There is evidence that childhood traumatic brain injury (TBI) is associated with increased risk of offending and violent crime. This study aimed to explore associations between TBI in a group of delinquent and vulnerable young people (VYP) at risk of offending, and facial emotion recognition (FER) abilities, inhibition control (Stop-IT) and self-reported reactive-proactive aggression (RPQ). Methods: There were two studies. The first study used a cross sectional between group design to compare 45 VYP (with and without TBI) and a control group of 59 students on FER task measuring emotion recognition accuracy of six basic emotions. The second study examined differences between TBI and non-TBI groups in the VYP sample (N=21) on a Stop-IT task, FER accuracy and self-reported reactive-proactive aggression. Results: A history of TBI was reported by 60% of the VYP group (48.9% with loss of consciousness [LoC]), whereas 30% of the control group reported a history of TBI (25.4% with LoC). The VYP group (with and without TBI) demonstrated a similar pattern of reduced overall FER accuracy that was significantly different to the control group. Compared to the control group, The VYP groups (with and without TBI) were less accurate on recognising anger, disgust, sadness and surprise, but not happy and fear. There were no significant differences between the TBI- and non-TBI groups. The second study did not find any significant differences between the TBI and non-TBI groups on overall FER accuracy, Stop-IT performance, and RPQ scores. There were also no significant associations between these measures. Conclusions: Future research requires larger samples that enable investigating the association between different severity of TBI, FER and inhibition control ability. Better and more youth-friendly measures are also needed.

Traumatic brain injury (TBI) remains an important cause of morbidity and mortality within society. TBI may result in both focal and diffuse brain injury. Diffuse traumatic axonal injury (TAI) is an important pathological substrate of TBI, and can be associated with a range of clinical states, ranging from concussion through to death, the clinical severity being associated with a number of factors related to the injury. A retrospective study was conducted using 406 cases with TBI, from the archive of the Academic Department of Pathology (Neuropathology) University of Edinburgh, during the period from1982 and 2005. This cohort was sequential and provided a unique description of the range of pathologies associated with fatal TBI within the Edinburgh catchment area. All the data was collected on a proforma and analysed to provide a description of the incidence in the injury patterns among the Edinburgh cohort. This cohort was then used to provide cases to try and critically assess the mechanisms of axonal injury in TBI. A study was undertaken to investigate TAI in an experimental model of non-impact head injury in a gyrencephalic mammalian model (piglet model) and in human autopsy materials using immunohistochemical analysis of a range of antibodies, and to define the distribution of axonal injury with flow and neurofilament markers in TAI. A further objective was to examine the expression of β-APP as an indicator of impaired axonal transport, three neurofilament markers targeting NF-160, NF-200, and the phosphorylated form of the neurofilament heavy chain (NFH), in different anatomical regions of piglet and human brains. The double immunofluorescence labelling method was then employed to investigate the hypothesis of co-localisation between β-APP and each one of the previous neurofilament markers. The animal studies showed significant differences in NF-160 between sham and injured 3-5 days old piglet cases (6 hour survival) and between 3-5 days sham and injured, when stained with SMI-34 antibody. In 4 weeks old piglet cases (6 hour survival), immunoreactivity of β-APP was significantly higher in injured than control. No other significant differences for any of the antibodies were noted, based on age, velocity, and survival time. Human results suggested that the brainstem had a higher level of β-APP and NF-160 than the corpus callosum and internal capsule. Co-localisation of β-APP with NFs was not a consistent feature of TAI in piglet and human brains, suggesting that markers of impaired axonal transport and neurofilament accumulation are sensitive to TAI, but may highlight different populations involved in the evolution of TAI.

The small GTPases function as molecular switches to control diverse signaling cascades. The mammalian Rit and Rin, along with Drosophila Ric, comprise an evolutionarily conserved subfamily of the Ras-related GTPases. Previous studies using cultured cell models suggested that Rit was involved in the control of cell proliferation, transformation, neuronal differentiation, morphogenesis, and cell survival, but the principal physiological function of Rit remained uncharacterized. To address this outstanding question, we employed a genetic approach, engineering a Rit knockout mouse. Using this animal model, we demonstrate a central role of Rit in governing cell survival in a p38-dependent fashion. Primary mouse embryonic fibroblasts (MEFs) derived from Rit-/- mice display increased apoptosis and selective disruption of MAPK signaling following oxidative stress. These deficits include a reduction in ROS-mediated stimulation of a novel p38-MK2-HSP27 signaling cascade, which appears to act upstream of the mTORC2 complex to control Akt-dependent cell survival. In the adult brain, proliferation of stem cells within the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG), provide a lifelong supply of new neurons. Adult neurogenesis appears critical for learning and memory and is altered in animal models of brain injury and neurological diseases. Thus, a greater understanding of the regulation of adult neurogenesis will provide insight into its myriad physiological roles but also to the development of therapeutic strategies for the treatment of injury and the progression of brain diseases. Here we find that Rit plays a central role in governing the survival of hippocampal neurons in response to oxidative stress. Importantly, using a controlled cortical impact model of traumatic brain injury (TBI), we show that Rit acts to protect newborn immature neurons within the SGZ of the DG from apoptosis following TBI. Finally, studies indicate that Rit plays a significant role in directing IGF-1 signaling, a key neurotrophin known to promote neurogenesis and to protect neurons against apoptotic stress. Together, these studies establish Rit as a critical regulator of a p38 MAPKdependent signaling cascade that functions as an important survival mechanism for cells in response to oxidative stress, including the survival of newborn hippocampal neurons in the traumatically injured brain.