Mild traumatic brain injury (mTBI) accounts for approximately 73-83% of all traumatic brain injuries (TBI) and continues to be a serious clinical challenge [1]. The role of injury mechanism in TBI has been widely debated, and it is believed that although there are differences between diffuse and focal TBI, the resulting injury is not influenced by the way in which it was acquired [1], [2]. It is known that TBIs can cause cognitive impairments that are often due to injury experienced in the hippocampus [2]. In response to insult, quiescent neural stem cell (NSC) populations within the dentate gyrus region of the hippocampus become activated. Stem cell differentiation following injury is hypothesized to be unique for diffuse and impact TBIs, primarily due to the differences in mechanotransduction pathways triggered by each respective injury. By quantifying the lineage of stem cells through immunohistochemistry, this study examined the dentate gyrus following mTBI in a rodent model, and the contribution that injury mechanism plays in mTBI outcomes. Additionally, the behavioral effects of mTBI were assessed through open field testing at 72 hours and four weeks following injury. Overall, these findings indicated that after four weeks following mTBI, there are not significant differences between impact and blast both from an immunohistochemical and behavioral standpoint. Despite there being few differences between injury groups, these findings help clarify the role of injury mechanism not only in the context of neurogenesis, but they also inform future studies addressing preventative and treatment strategies for mTBI. / Master of Science / Mild traumatic brain injury (mTBI) accounts for approximately 73-83% of all traumatic brain injuries (TBI) [1]. There are two main ways in which a mTBI can occur: through diffuse or focal injury. A diffuse injury is due to the brain experiencing a force that does not physically come into contact with the head, such as a shockwave from an explosion. These types of injuries typically affect the entire head. Impact injuries on the other hand, are caused by the head encountering an object at a force that causes injury to the brain. These injuries tend to be focal, as the entire head rarely comes into contact with an object. Both diffuse and focal injuries can cause mTBI, and there is a current debate questioning if the mode of injury has an impact on the damage experienced by the brain [1], [2]. However, it is also known that mTBI can cause cognitive impairments such as changes in behavior, memory, and even mental health, which can occur in the hippocampus of the brain [2]. Within the hippocampus, there is a small subset of cells referred to as neural stem cells (NSC) that become active following injury. The activation of these cells is believed to be in response to injury in the brain. Furthermore, NSCs have the ability to differentiate into various cell types within the brain, including astrocytes, oligodendrocytes, and neurons. Each of these cell types perform an integral role in the function of the brain. It is hypothesized that the response of NSCs in the hippocampus is unique depending on if an injury was acquired through diffuse or impact mechanisms. To investigate this, the lineage of NSCs was quantified within the hippocampus following blast and impact mTBI in a rodent model. Additionally, the behavioral effects of diffuse and impact injury were investigated at 72 hours and four weeks following injury. Despite there being no significant differences in outcomes between injury groups, these findings help clarify the role of injury mechanism not only in the context of NSC response, but they also inform future studies addressing preventative and treatment strategies for mTBI.

La prévalence des troubles du sommeil et de douleur chronique est élevée chez le patient ayant subi un traumatisme crânien cérébral léger (TCCL). L’interaction entre ces plaintes est suggérée chez les patients avec un TCCL mais son étiologie reste encore peu connue. Les résultats de recherche présentés dans le premier article de cette thèse suggèrent que les patients avec un TCCL qui souffrent de douleur ont une modification des ondes cérébrales durant leur sommeil, ce qui pourrait expliquer en partie comment les deux symptômes interagissent. De plus, la douleur, surtout si associée à des troubles de l’humeur, semble jouer un rôle majeur dans la persistance des symptômes post-commotionnels. Le deuxième article de cette thèse décrit une exacerbation des symptômes post-commotionnels chez le patient ayant eu un TCCL et souffrant de douleur. La persistance ou l’apparition de la douleur chronique à long terme serait prédite par le polymorphisme val66met du gène brain-derived neurotrophic factor (BDNF). Une étude subséquente, présentée dans le troisième article, nous a permis d’approfondir les bases génétiques et cellulaires du rôle du BDNF dans la persistance des symptômes post-commotionnels. Des polymorphismes fréquents dans le gène BDNF ont révélé des variantes liées au mauvais pronostic suite à un TCCL. De plus, l’analyse de cellules extraites de patients ayant subi un TCCL démontrent que l’expression de la protéine BDNF peut être modifiée chez le patient de génotype met66 et ayant subi un TCCL, lui conférant ainsi un rôle neuroprotecteur potentiel. En résumé, nous avons tenté de démontrer dans cette thèse que la douleur suite à un TCCL joue un rôle important dans les perturbations du sommeil et dans la persistance des symptômes post-commotionnels. Une prédisposition génétique pourrait contribuer à expliquer le mauvais pronostic et la chronicité des symptômes post-commotionnels suite à un TCCL. / Mild traumatic brain injury (MTBI) is a major public health concern as patients are left, amongst other symptoms, with sleep complaints and chronic pain. An interaction between these symptoms is suggested. For instance, a night of poor sleep is usually followed by hypersensitivity to pain and chronic pain always leads to sleep complaints. This interaction is suggested following an MTBI, however, data sustaining that hypothesis are still lacking. Data from the first article suggest that pain and other post-concussion symptoms are correlated with sleep-wake disturbances post-MTBI. MTBI patients with pain have more rapid electroencephalographic (EEG) waves during sleep than those without pain. This may suggest that there is an intrinsic physiological relationship between the two complaints. Moreover, pain seems to play an important role in the persistence of post-concussive symptoms. The second article of this thesis describes and details the exacerbation of post-concussive symptoms in the presence of pain following MTBI. The val66met polymorphism in the Brain-derived neurotrophic factor (BDNF) gene is an important predisposing factor for chronic pain. Lastly, a subsequent study, presented in the third article details the genetic and cellular basis of the role of BDNF in the persistence of post-concussive symptoms. Common polymorphisms in the BDNF genes were genotyped and revealed variants related to post-concussive symptoms following MTBI. Moreover, protein expression studies in lymphoblast cells of MTBI patients showed a modified expression of BDNF with the met genotype that might be neuroprotective. In summary, this thesis first shows that pain contributes to sleep-wake disturbances following MTBI and that the chronicity of post-concussive symptoms, including chronic pain, may be dependent on polymorphisms in the BDNF gene.

While multiple Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn veterans suffer from mild Traumatic Brain Injury (mTBI), Post-traumatic Stress Disorder (PTSD), and co-morbid mTBI and PTSD, there remains difficulty disentangling the specific symptoms associated with each disorder using self-report and neurocognitive assessments. We propose that neurological soft signs (NSS), which are tasks associated with general neurologic compromise, may prove useful in this regard. Based on our review of the literature we hypothesized that individuals with PTSD would present with a greater number of NSS than controls or individuals with mTBI. Further, we hypothesized a synergistic effect, such that individuals with mTBI + PTSD would present with the greatest number of NSS. To test these hypotheses, we analyzed a subset of individuals (N=238) taken from a larger study of neurocognitive functioning in veterans. Participants completed a battery of neuropsychological measures, which included the Behavioral Dyscontrol Scale (BDS), the current study’s measure of NSS. A subset of other neuropsychological measures were also included to examine the utility of NSS over and above traditional neuropsychological measures. Individuals were removed from the study if they sustained a moderate/severe TBI or did not meet validity criteria on the Green’s Word Memory Test or the Negative Impression Management subscale of the Personality Assessment Inventory. Binomial logistic and multinomial logistic regression were used to examine the ability of NSS to discriminate between the study groups, first by themselves and then after the variance explained by the traditional neuropsychological measures was accounted for. Exploratory cluster analyses were performed on neuropsychological measures and NSS to identify profiles of cognitive performance in the data set. Results indicated that individuals in the mTBI and/or PTSD group had more NSS compared to controls. Of the individual NSS items only a go/no-go task of the BDS discriminated between groups, with worse performance among individuals in the mTBI, PTSD, and mTBI + PTSD group compared to controls. In contrast, the overall BDS score and individual NSS, in general, did not discriminate between the mTBI, PTSD, and mTBI + PTSD group. Overall, the current study suggests that, when eliminating participants who do not meet validity criteria, NSS do not aid in discriminating between individuals with mTBI, PTSD, and mTBI + PTSD.

Concussion affects the adolescent population in large numbers, primarily because of the popularity of team sports that are played in middle and high school. This adolescent age group is more susceptible to the adverse effects of concussion due to physiological immaturity, and recovery for this population takes longer than in adults. Speech-language pathologists, who are trained to treat cognitive-communication deficits, are present in the majority of school systems throughout the United States, and could be a useful resource to manage and treat students who incur concussion. However, speech-language pathologists historically have not treated students with concussion, and may not be receiving adequate education regarding concussion in graduate programs. This study sought to ascertain the education, training, and experience regarding concussion of speech-language pathologists in Texas secondary schools. Anonymous survey responses were collected via an Internet survey platform, yielding 49 respondents for the final data pool. The answers provided by these respondents indicate Texas speech-language pathologists are not yet receiving adequate concussion education and training. Respondents reported low confidence levels in several key areas of concussion knowledge, and doubt regarding the speech-language pathologist's role in managing concussion. Recommendations include concussion-targeted graduate school curriculum as an extension of traumatic brain injury curriculum, increased continuing education efforts by ASHA regarding concussion and the speech-language pathologist's role in treating concussion, and further advocacy by ASHA for speech-language pathologists to be part of concussion management teams based in schools. / text

La prévalence des troubles du sommeil et de douleur chronique est élevée chez le patient ayant subi un traumatisme crânien cérébral léger (TCCL). L’interaction entre ces plaintes est suggérée chez les patients avec un TCCL mais son étiologie reste encore peu connue. Les résultats de recherche présentés dans le premier article de cette thèse suggèrent que les patients avec un TCCL qui souffrent de douleur ont une modification des ondes cérébrales durant leur sommeil, ce qui pourrait expliquer en partie comment les deux symptômes interagissent. De plus, la douleur, surtout si associée à des troubles de l’humeur, semble jouer un rôle majeur dans la persistance des symptômes post-commotionnels. Le deuxième article de cette thèse décrit une exacerbation des symptômes post-commotionnels chez le patient ayant eu un TCCL et souffrant de douleur. La persistance ou l’apparition de la douleur chronique à long terme serait prédite par le polymorphisme val66met du gène brain-derived neurotrophic factor (BDNF). Une étude subséquente, présentée dans le troisième article, nous a permis d’approfondir les bases génétiques et cellulaires du rôle du BDNF dans la persistance des symptômes post-commotionnels. Des polymorphismes fréquents dans le gène BDNF ont révélé des variantes liées au mauvais pronostic suite à un TCCL. De plus, l’analyse de cellules extraites de patients ayant subi un TCCL démontrent que l’expression de la protéine BDNF peut être modifiée chez le patient de génotype met66 et ayant subi un TCCL, lui conférant ainsi un rôle neuroprotecteur potentiel. En résumé, nous avons tenté de démontrer dans cette thèse que la douleur suite à un TCCL joue un rôle important dans les perturbations du sommeil et dans la persistance des symptômes post-commotionnels. Une prédisposition génétique pourrait contribuer à expliquer le mauvais pronostic et la chronicité des symptômes post-commotionnels suite à un TCCL. / Mild traumatic brain injury (MTBI) is a major public health concern as patients are left, amongst other symptoms, with sleep complaints and chronic pain. An interaction between these symptoms is suggested. For instance, a night of poor sleep is usually followed by hypersensitivity to pain and chronic pain always leads to sleep complaints. This interaction is suggested following an MTBI, however, data sustaining that hypothesis are still lacking. Data from the first article suggest that pain and other post-concussion symptoms are correlated with sleep-wake disturbances post-MTBI. MTBI patients with pain have more rapid electroencephalographic (EEG) waves during sleep than those without pain. This may suggest that there is an intrinsic physiological relationship between the two complaints. Moreover, pain seems to play an important role in the persistence of post-concussive symptoms. The second article of this thesis describes and details the exacerbation of post-concussive symptoms in the presence of pain following MTBI. The val66met polymorphism in the Brain-derived neurotrophic factor (BDNF) gene is an important predisposing factor for chronic pain. Lastly, a subsequent study, presented in the third article details the genetic and cellular basis of the role of BDNF in the persistence of post-concussive symptoms. Common polymorphisms in the BDNF genes were genotyped and revealed variants related to post-concussive symptoms following MTBI. Moreover, protein expression studies in lymphoblast cells of MTBI patients showed a modified expression of BDNF with the met genotype that might be neuroprotective. In summary, this thesis first shows that pain contributes to sleep-wake disturbances following MTBI and that the chronicity of post-concussive symptoms, including chronic pain, may be dependent on polymorphisms in the BDNF gene.

<p><bold>Abstract</bold></p><p>More than 300,000 soldiers have returned from Southwest Asia (i.e., Iraq and Afghanistan) with combat-related mild traumatic brain injuries (mTBIs) associated with exposure to improvised explosive devices (IEDs). Despite less visible physical injuries, these soldiers demonstrate varying levels of physical and cognitive symptoms that impact their post-mTBI family reintegration. The existing literature acknowledges post-mTBI changes in the injured individual affect family functioning; however, post-injury family functioning, such as coping and adaptation, has not been explored. The intent of this dissertation is to explore the problems and challenges of military family reintegration following mTBI.</p><p>Nine soldiers with mTBI and their spouses participated for a total of 27 interviews. Both joint and separate individual interviews were conducted to explore their post-mTBI family reintegration experiences. Participants included active duty soldiers with mTBI who were between 2 and 24 months post-deployment and their civilian spouses. Strauss and Corbin's grounded theory methodology was used to collect and analyze the data. This dissertation study consists of three papers, each of which explored experiences that surround family reintegration following mTBI.</p><p>The first paper is a comprehensive literature review, examining commonly reported mTBI signs/symptoms, and the impact of these symptoms on the injured individuals and their families. The findings also suggest that psychological distress symptoms such as depression and anxiety are common in injured individuals and their</p><p>families after mTBI. The second paper explores the family reintegration processes of post-mTBI soldiers and their spouses. The majority of participants interviewed, both soldiers and their spouses, indicated that symptoms such as irritability, memory loss, and cognitive deficit affected their family reintegration. Some participants reported they had accepted the changes and were working toward a new normal, whereas others indicated these changes were unacceptable and continued their efforts to resume pre-injury functioning.</p><p>The third paper examined the experiences of soldiers and their spouses about seeking treatment for mTBI-related symptoms. The majority of interviewed soldiers and their spouses indicated that a delayed diagnosis, difficulty accessing mental health care, and having to navigate an unfamiliar military healthcare system were their biggest challenges. Post-mTBI soldiers experienced significant disruption due to mismatched expectations among themselves and other family members concerning their post-injury capabilities. More research is needed in order to develop effective post-injury rehabilitation programs for soldiers with mTBI and their families.</p> / Dissertation

Objectives: To explore the prevalence and structure of self-reported disability after mild traumatic brain injury and the impact of traumatic brain pathology on such outcome. Material and methods: In study 1-3, symptoms data were collected by use of Rivermead Post-concussion Symptoms Questionnaire (RPQ) and data on global function by use of Glasgow Outcome Scale Extended (GOSE) from 2602 patients at 3 months after MTBI. RPQ data were subject to factor and Rasch-analyses Head CT data from 1262 patients were used in a prediction analysis that also included age and gender. In study 4, MRI and symptoms data were collected at 2-3 days and at 3-7 months follow-up after MTBI in 19 patients. Global function was assessed at follow-up by use of the Rivermead Head Injury Follow-Up Questionnaire (RHIFUQ) and GOSE. Results: I. Most respondents reported no remaining symptoms but 24% reported ≥3 and 10% ≥7 remaining symptoms. The factor analysis demonstrated that all symptoms are correlated but also identified subgroups of symptoms. II. Rasch-analysis of RPQ showed disordered category function, local dependency of items, poor targeting of persons to items and indications of 3 or more dimensions. There was no differential item functioning. III. Head CT pathology with no need for acute intervention was observed in 52 patients (4%) but was not associated with either frequency of remaining symptoms or global outcome at 3 months post injury. Female gender and age over 30 years were associated with less favourable outcome with respect to symptoms and GOSE. IV. Post-acute MRI indicated trauma-related pathology in one patient and follow-up MRI indicated loss of brain volume in 4 patients. Conclusions: A substantial proportion of patients with MTBI report remaining problems at three months after MTBI. RPQ is useful but not optimal to assess symptoms outcome after MTBI and calculation of a total sum score is not recommended. Female gender and older age are negative prognostic factors while brain pathology according to CT has no effect on self-reported outcome. Loss of brain volume after MTBI according to MRI may be a sensitive marker of traumatic brain pathology and deserves further studies.

Thesis (M.A.)--Miami University, Dept. of Speech Pathology and Audiology, 2004. / Title from first page of PDF document. Includes bibliographical references (p. 54-59).

Objectives: After mild traumatic brain injury (mTBI), psychological factors can contribute to persisting post-concussion symptoms (PCS). Consistent with constructive theories of memory, negative expectations for increased symptoms after mTBI may contribute to misattributing symptoms to the mTBI and underestimating pre-injury symptoms, called the “good old days’ bias” (Gunstad & Suhr, 2001). The good old days’ bias is not thought to be a general retrospective recall bias but studies to date have largely not controlled for normative memory processes including those that lead to a biased, more positive recall of the past. Therefore, the current study examines whether there is a good old days’ bias after mTBI above and beyond normal memory biases. This study also examines how soon after mTBI the good old days’ bias affects recall of pre-injury symptoms in the first month after mTBI in adolescents as well as whether the good old days’ bias causes pre-injury symptom severity to be underestimated or if symptoms are entirely forgotten. Finally, the clinical significance of symptom recall biases is investigated. Method: The sample is 42 adolescents who sustained an mTBI (ages 13-18 years; 24 males) and 42 uninjured adolescents (ages 13-18 years; 24 males, ). The mTBI group rated current and retrospective post-concussion symptom ratings within one week and again, at one month, post-injury. The control group rated current and retrospective post-concussion symptoms at baseline and one month later. Cross-sectional and longitudinal comparisons using non-parametric statistical tests were used. Results: Wilcoxon signed-rank tests showed that, by one month post-mTBI, adolescents report fewer total, physical, and emotional pre-injury symptoms than they had reported within one week of their concussion. The control group did not demonstrate this good old days’ bias. There were no between-group differences in retrospective PCS ratings at either time point. Chi-square analyses found that the mTBI group was as likely as the control group to recall “no” pre-injury/past symptoms one month post-injury after having initially reported some pre-injury symptoms. Only four more adolescents were classified as “recovered” if their one-month PCS ratings were compared with pre-injury PCS ratings made within 1-week post-concussion rather than pre-injury ratings from 1-month post-injury. Discussion: There was mixed evidence for a good old days’ bias by one month post-concussion. This bias was not demonstrated in healthy adolescents, suggesting that the good old days’ bias is found specifically after concussion. During the acute post-injury period, the good old days’ bias may only be apparent by studying changes in concussed individuals’ own PCS ratings. The good old days’ bias leads to underestimating the severity of pre-injury symptoms rather than forgetting them entirely. The good old days’ bias does not greatly affect symptom recovery tracking by one month post-concussion. Future studies should directly examine expectations about concussion and their effect on current and retrospective symptom reporting. / Graduate / 2019-07-10

A complete understanding of the functional and structural impairments driving persistent post-concussive symptom (PCS) expression in approximately one-third of those who suffer from mild traumatic brain injury (mTBI) is essential for the development of effective treatment strategies and improving quality of life. While traditional outcome measures, such as neuropsychological testing and structural magnetic resonance imaging, are sensitive to the severe functional impairments and widespread tissue damage frequently seen after moderate-to-severe injuries, more advanced measures that are sensitive to the subtle changes in cognitive function and tissue microstructure that may underlie persistent PCS are necessary for the assessment of recovery from mTBI. Toward this end, the current study investigates the utility of eye-tracking analysis and high-definition fiber tractography (HDFT) as advanced measures of functional and microstructural outcome in 11 adults with chronic mTBI and varying levels of PCS (ages 20-60; mean time post-injury = 9.53 ± 6.74 years) in comparison to 10 healthy adults (ages 20-54). Performance on neuropsychological and eye-tracking tasks of processing speed, attention, and working memory, and HDFT-derived quantitative measures of the microstructural integrity of the forceps major, inferior fronto-occipital fasciculus, middle longitudinal fasciculus, and superior longitudinal fasciculus were compared between groups, and the results were used to define discriminatory functions for mTBI classification. The relationships between neuropsychological and eye-tracking measures of cognitive function and HDFT-derived measures of tract integrity were explored, as was the utility of these functional and structural measures for predicting persistent PCS in chronic mTBI. The results suggest that eye-tracking analysis may be more specific to cognitive impairments resulting from mTBI than neuropsychological testing, and HDFT is highly sensitive and specific to the subtle microstructural changes that persist chronically in this population. Furthermore, white matter integrity assessed using HDFT is more strongly associated with impairments in processing speed, attention, and memory indicated through eye-tracking analysis relative to performance on neuropsychological tests. Finally, although the predictive utility of eye-tracking and HDFT for the experience of persistent PCS was not demonstrated in the present sample, the possibility that these data are confounded by symptom exaggeration, comorbid mental health impairment, or lack of self-awareness for functional deficits cannot be ruled out, and future research using large, homogenous sample of mTBI is necessary to validate the present findings.