Researchers studying the long-term cognitive sequelae of mild traumatic brain injury (mTBI) have produced disparate results. Some studies have shown little to no long-term cognitive effects while others have shown that persistent cognitive sequelae continue to affect a subgroup of patients. Meta-analysis has been used to try to integrate these contrasting results to foster a coherent understanding of the cognitive outcomes following mTBI. However, previous meta-analyses of long-term cognitive sequelae have used studies from a period of mTBI research where methodological rigor has been called into question (Carroll, Cassidy, Holm, Kraus, & Coronado, 2004). Using studies from this period, meta-analysts found little to no effect for long-term cognitive sequelae after mTBI: g = 0.07, d = 0.12 (Binder, Rohling, & Larrabee, 1997), g = 0.11(Frencham, Fox, & Mayberry, 2005), and d = -0.07 (Rohling et al., 2011). The present meta-analysis was conducted to address problems with methodological rigor in the studies used in these previous meta-analyses and address differences in meta-analytic methodology (Pertab, James, & Bigler, 2009). Studies published between January 2003 and August 2010 were rated using the 4-tiered American Academy Neurology (AAN) guidelines for methodological rigor to ensure homogeneity and the methodological rigor of included studies. Seven studies were identified that met criteria for a rating of I or II and five met criteria for the lower ratings of III or IV. When studies of all ratings were combined, a significant effect of g = 0.45 was observed. When only studies rated I and II were combined, a significant effect of g = 0.52 was observed while a significant effect of g = 0.38 was observed when only studies rated III and IV were combined. These effect sizes for long-term cognitive sequelae are much larger than those found in previous meta-analyses. Based on these results, it is likely that methodological rigor and/or heterogeneity amongst included studies can impact meta-analytic effect sizes associated with long-term cognitive sequelae following mTBI. However, analyses did not show that more rigorous studies (i.e., those rated I or II) had significantly higher effect sizes than less rigorous studies (i.e., those rated III or IV), t(10) = .636, p = .845. This non-significant finding may be a result of the analysis being underpowered given the small k. Significant effects for neuropsychological domain were also observed and are reported. Additionally, a conceptual critique of mTBI is made with recommendations for future development of the rating system that Cappa, Conger, and Conger (2011) have put forth for objectively rating the methodological rigor of neuropsychological studies. Concerns are addressed related to the mTBI literature in the areas of mTBI definition, definition of cognitive impairment, problems with the constructs of post-concussion syndrome (PCS) and persistent post-concussion symptoms (PPCS), heterogeneity of outcome measurement, and unaccounted for variables.

With the advancement of protective gear and medical aid, soldiers are now surviving traumatic experiences that were once fatal. As a result, the prevalence of brain injury and posttraumatic stress disorder in military service members has grown. Those who have obtained brain injury are at risk of developing chronic traumatic encephalopathy, a neurodegenerative syndrome. To date, there is no cure, treatment, or diagnostic method (besides autopsy) for chronic traumatic encephalopathy. Because chronic traumatic encephalopathy and posttraumatic stress disorder present many of the same symptoms and have the possibility of deriving from the same traumatic experience, an investigation of a potential link is necessary. This study explores the possibility of chronic traumatic encephalopathy being misdiagnosed as posttraumatic stress disorder. This is done by analyzing the frequency of brain injury along with the comorbidity of posttraumatic stress disorder and brain injury. This thesis also proclaims the need for research that attempts to develop diagnostic criterion and treatment methods for chronic traumatic encephalopathy.

BACKGROUND: Several groups have instituted helmet initiatives with varying success across the world. Helmet use has been well documented to prevent traumatic brain injury. Despite the known benefits, many people, including university students, refuse to utilize helmets when riding bikes, mopeds, or motorcycles. We recognized a need within our community regarding the lack of helmet use at University of Florida and developed a program to institute change. METHODOLOGY: We identified community champions and hosted weekly round table discussion initiatives. Through these round table discussions we identified events already going on within the community and developed new opportunities to promote helmet use. We had stories from survivors and parents, utilized school administration support, and partnered with local bike shops. RESULTS: The pilot initiative was successful in increasing awareness across the city and got stakeholders excited in the process. It also spearheaded more data driven initiatives that will look at reduction of traumatic brain injuries in the clinical setting. CONCLUSION: This project highlights the University of Florida Helmet Initiative that has already generated renewed interest in safety and traumatic brain injury prevention. The school of nursing has implemented safety protocols and further support is being garnered by the administration across campus. Most importantly we have identified community champions that will carry the work forward.

Blast-induced traumatic brain injury and hearing loss are two of the most common forms of the “invisible wounds of war” resulting from the United States’ Global War on Terror. Several published studies have been confirming recent reports from VA healthcare centers of blast-exposed Service Members complaining of auditory problems despite having hearing that is, for all intents and purposes, normal. Most common among these complaints is problems understanding speech in crowded and noisy situations. We hypothesized that problems with speech comprehension could either be the result of 1) damage to sensory areas in the auditory periphery or 2) blast-induced traumatic brain injury (TBI) to cortical networks associated with the processing of attention, memory, and other executive functions related to the processing of speech and linguistic information. In Chapter 1 of this thesis, we found that in a population of blast-exposed Veteran Service Members, problems with speech comprehension in noise were due to cognitive deficits likely resulting from issues related to their post-traumatic stress disorder (PTSD) diagnoses. Chapter 2 takes and expanded look at the topics of Chapter 1 with a more comprehensive battery of audiological, electrophysiological, and neuropsychological tests in active duty Service Members with and without a history of blast exposure. Unlike in veterans with PTSD, we found subclinical levels of peripheral auditory dysfunction, as well as evidence of compromised neural processing speed in the blast-exposed group. These deficits were also consistent with poorer performance on a standardized speech-in-noise test and lower self-reported ratings on an abbreviated version of the Speech, Spatial, and Qualities (SSQ) of Hearing questionnaire (Gatehouse and Noble, 2004). In Chapter 3,we modeled outcomes from the SSQ survey using objective measures of hearing function related to audibility, distortion of the neural representation of sound, attention, age, and blast status. We found for all subjects age and high frequency hearing thresholds predicted survey outcomes related to everyday listening ability. Within non-blast controls, however, measures of attention could differentiate between good and exceptional listening ability. Results from blast exposed subjects remained inconclusive. Collectively, these findings highlight the need for audiologists to take into account more than audiometric measures alone when diagnosing and treating hearing dysfunction in this unique and specialized patient population.

The Intensive Cognitive and Communication Rehabilitation program (ICCR), developed to advance young adults with acquired brain injury (ABI) to college, targets a range of cognitive domains (e.g., memory, writing, verbal expression) via classroom-style lectures, individual therapy, and technology- and computer-based interventions on an intensive schedule (i.e., six hours/day, four days/week, 12-week iterations). One of the driving hypotheses of this dissertation work is that cognitive rehabilitation programs that are embedded with principles of experience-dependent neuroplasticity (i.e., repetition, intensity, specificity, salience), like ICCR, should lead to changes in behavior and the brain. The initial two studies of this dissertation focused on the first aspect of this hypothesis (i.e., assessing the impact of ICCR on overall cognitive-linguistic function and specific cognitive domains important for academic success in young adults with ABI), while the final two studies addressed the second aspect (i.e., using fNIRS to measure brain activation during language and domain-general cognitive tasks in neurotypicals and individuals with ABI at a single timepoint and over time). In Study 1, young adults with ABI who participated in ICCR demonstrated significant gains in at least one standardized assessment of global cognitive-linguistic function, while control participants did not. Yet, the study did not reveal what specific cognitive domains important for academic success improved after the ICCR program—an essential intermediate step in evaluating the utility of these programs in preparing young adults with ABI for academic reentry. Study 2 addressed this unanswered question with a novel approach that aggregated items from standardized neuropsychological assessments into specific cognitive domains (e.g., attention, verbal expression, memory) and then, applied growth curve modeling to assess whether those domains improved significantly over time in young adults with ABI participating in the ICCR program. This study also directly compared whether the treatment group improved at a significantly faster rate in overall item accuracy and subdomain item accuracy than a deferred treatment/control usual care group, extending the findings from Study 1 with a larger participant sample. Study 3 was a pilot study using fNIRS to capture brain activation in expected regions during language and domain-general cognitive processing in neurotypicals and individuals with stroke-induced aphasia. Findings from the young healthy control group in this study would serve as a reference for interpreting brain activation patterns in the damaged brain in future work. This study also provided opportunities to determine the acceptability of the fNIRS behavioral tasks and acquisition procedures for individuals with stroke-induced aphasia and to assess the utility of a novel method for managing areas of lesion. Based on the robust findings of Study 1 and 2 (i.e., ICCR promoted gains in overall cognitive domains and specific cognitive processes important for college success) and the promising results of Study 3 (i.e., activation patterns during language and domain-general cognitive processing could be captured in neurotypicals and individuals with brain damage at a single timepoint using fNIRS), Study 4 was undertaken to assess pre- to post-treatment activation changes following ICCR participation via fNIRS. Five young adults with ABI underwent fNIRS measurement while performing the same behavioral task battery used in Study 3 (i.e. semantic feature, picture naming, arithmetic) before and after a 12-week semester of ICCR. This preliminary work provided opportunities 1) to apply fNIRS to measure treatment-related neuroplasticity in the ABI population; 2) to examine the extent to which treatment participants demonstrated changes in the brain following ICCR in conjunction with a positive treatment response and improved behavioral task accuracy; and 3) to identify methodological considerations for future studies in this area. In closing, this dissertation reviews key findings from each of these studies and discusses their implications for studying rehabilitation-induced recovery in adults with ABI in future work. / 2023-08-06T00:00:00Z

Every year millions of individuals suffer from traumatic brain injury (TBI) leading to permanent disabilities and even death. Mild TBI (mTBI) is the most common form of TBI comprising about 80-90% of all occurrences. Following a CNS insult like an mTBI, astrocytes can undergo activation resulting in the transformation into reactive astrocytes (RAs). RAs also play an important role in brain remodeling following an mTBI. Research on the mechanical complexity of the brain has important implications for understanding brain function and dysfunction, as well as for the development of new diagnostic and therapeutic tools for neurological disorders. This study aimed to develop and utilize an emph{in vitro} mTBI platform to investigate the intricate mechanical interplay between the extracellular matrix (ECM) and astrocytes following a simulated mTBI. Cellular mechanisms underlying mTBI and the contribution of mechanical forces that result in prolonged brain damage are yet to be comprehensively understood. Successfully devised mechanical characterization techniques for tissue-engineered models were developed utilizing atomic force microscopy and rheology. Astrocyte exposure to high-rate overpressure revealed altered mechanical properties of the surrounding matrix and decreased expression of laminin and collagen IV, which are critical for brain function and may contribute to pathologies associated with mTBI. The developed platform and methods provide new insights into the mechanistic complexity underlying ECM-astrocyte interactions following an mTBI. / Master of Science / Every year, millions of people suffer from traumatic brain injury (TBI), which can lead to permanent disabilities or even death. The most common form of TBI is mild TBI (mTBI), which accounts for 80-90% of all cases. After a mTBI, astrocytes, the most common cell type in the brain, can become activated and turn into reactive astrocytes (RAs). RAs play an important role in the brain's recovery following a mTBI. Understanding the mechanical complexity of the brain is crucial for developing new diagnostic and therapeutic tools for neurological disorders. This study aimed to investigate the mechanical interplay between the modeled tissue and astrocytes following a simulated mTBI using an emph{in vitro} platform. Development of mechanical characterization techniques allowed for any alterations caused by the astrocytes to their environment to be detectable. The astrocyte exposure to the simulated mTBI revealed altered mechanical properties of the surrounding environment and decreased expression of proteins laminin and collagen IV, which are critical to brain function and may contribute to pathologies associated with mTBI. This study provides new insights into the mechanistic complexity underlying the interaction between astrocytes and their environment, which could lead to the development of new treatments.

Both individual patient-related and injury-related factors predict functional outcomes following moderate-to-severe traumatic brain injury (M/S TBI). Other than binary outcomes such as death, little is known about the role of day-of-injury neuroimaging in predicting long- term outcomes. Classification systems for assessing the severity of injury using computerized tomography (CT) scans, such as the Marshall Classification System (MCS) or Rotterdam scale, have not been systematically studied to see how they relate to long-term rehabilitation and functional outcomes following M/S TBI. The MCS consists of six categories based on information about midline shift, basal cistern compression, surgery evacuation, and lesion size. The Rotterdam scale, however, is a summed score ranging from 1-6 based on the extent of basal cistern compression, extent of midline shift, presence/absence of an epidural lesion, and presence/absence of traumatic subarachnoid hemorrhage (tSAH) or intraventricular blood. The differences between these two CT scales suggest the possibility that MCS and Rotterdam scales may differ in their ability to predict subsequent rehabilitation outcomes. Thus, we compared the relative predictive value of MCS and Rotterdam scores on long-term rehabilitation functional outcomes using the Functional Independence Measure (FIM) at rehabilitation discharge and nine-month post-discharge follow up. The study included 88 participants (25 females, mean age: 42.0 [SD: 21.3]) with M/S TBI. Day-of-injury CT images were scored using both MCS and Rotterdam criteria. Functional outcomes were measured by the cognitive and motor subscales on the FIM at discharge and after nine-month follow up, and length of stay in rehabilitation. Data were analyzed using multiple linear regression models. Neither MCS nor Rotterdam scores nor rehabilitation length of stay significantly predicted motor or cognitive outcomes at discharge or nine-month follow-up. MCS and Rotterdam scales may have limited utility in predicting long- term functional outcome in a rehabilitation setting, but instead appear to be good predictors of acute outcomes, especially regarding mortality and elevated intracranial pressure (ICP). Future research could focus on CT characteristics such as midline shift to predict long-term rehabilitation outcomes to guide treatment instead of CT rating scales.

Traumatic brain injury (TBI) is a life-altering injury that can impact global functioning. The Centers for Disease Control (CDC) reports that yearly 2.2 million Americans experience a TBI, a large portion of whom are children and young adults who then face the prospect of attending university. Data emphasizes the number of younger individuals who may experience symptoms that can limit their ability to complete post-secondary education and continue on to the workforce (Allen & D'Amato, 2010). Individuals who experience a TBI have limited opportunities for advancement due to cognitive challenges and require additional support to achieve their full potential. To address the well-documented academic and employment-related obstacles that may await postsecondary students with TBI following their injuries, Project Career, a multi-site five-year initiative funded by the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) was designed to promote the use of cognitive support technology (CST) and intensive case management to improve employment success among college and university students with TBI. The changes in behavior, emotions, communication and physical health experienced after sustaining a TBI are unique to each person, highlighting a need for individualized treatment and support (Cicerone, 2002; Whyte, Polansky, Fleming, Coslett, & Cavallucci, 1995). “Peer Connections for Success: A mentoring program for university students with TBI” will seek to develop a program that uses peer interaction to create individualized support that is grounded in theory and informed by the evidence. Several theories will guide the creation of the intervention; Social Comparison Theory (Festinger, 1954) and Adult Learning Theory (Knowles, 1984) both of which contribute to the best methods of learning for this population. Programs such as this have been applied to different populations however the evidence is limited for use with students with TBI. Evidence was collected to support the methods, assessments, and processes that were utilized in the program.

Patients who suffer from traumatic brain injury often face communication deficits during their hospital stay. This thesis intended to examine approaches the nurse can use to facilitate communication in collaboration with the speech-language pathologist. A review of literature was conducted to examine current research on the most effective devices used to facilitate communication in this patient population. Research revealed that low-technology devices were the most effective means of communicating in the hospital setting. Barriers to effective communication were identified as lack of time, education and access to the devices. Recommendations for future research include developing a documentation component that emphasizes nursing assessment and intervention through collaboration with the SLP. Additional recommendations for research include the examination of impact of AAC use on patient satisfaction and outcomes. Communication using AAC is necessary in order to improve patient outcomes for traumatic brain injured individuals. This can be achieved through increased collaboration with the SLP, and increased nursing knowledge of the available devices and their implementation.

Traumatic brain injury (TBI) history has been linked to damaged cognition and poorer quality of life. While this link has been established, there is not much known about this relationship in older adult populations experiencing normal cognitive decline. In the current study, mental status was predicted to moderate the relationship between TBI history and life satisfaction among older adults. Additionally, details of the injury - years since injury and time spent unconscious - were expected to play a role in this relationship. Per analyses, there was no relationship found between TBI history, mental status, and life satisfaction. Moreover, there was no link found between time since injury, time spent unconscious, mental status and life satisfaction. While insignificant, these results yield important findings. The results lend support to more positive long-term outcomes for those with a history of TBI than initially expected, especially if the TBI was mild and resulted in no loss of consciousness or a loss of consciousness less than 5 hours.