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

An Acquired Brain Injury (ABI) can have lasting effects on the self-identity of the injured individual, but also on the self-identity of other family members. Using Contextual Family Stress Theory as a guiding theoretical framework, this qualitative study investigated how mothers experience changes and alterations in their self-identity and family identity, as well as the reconstruction of self-identity and family identity, after a child acquires an ABI. These experiences are important to capture so that clinicians and professionals may better understand the phenomenon of post-ABI self- and family identity and to help inform rehabilitation and professional services. Currently, research has been narrowly focused upon functional gains for individuals and families in rehabilitation while excluding changes in self-identity and family identity. Data were collected via semi-structured interviews and self-report measures of individual mothers' needs and perceptions of the injured child. A constructivist grounded theory analysis was used to analyze the data. Findings reveal the reconstruction processes of mothers' self-identity and family identity after a child receives an ABI, such as internal and external self-identity and intentionality in reconfiguring family identity. Furthermore, results suggest that positive adaptation in self-identity and family identity promote resilience to the changes from the child's ABI. Future research directions, theoretical, and clinical implications are discussed. / Doctor of Philosophy / An Acquired Brain Injury (ABI) can happen in many ways, such as a hard hit to the head or the brain not getting enough oxygen. Children and adolescents are among the age groups that have the highest rates of ABIs. The effects from an ABI are long lasting and impact the injured person in many ways, including their identity or sense of self. When a child receives an ABI, the parents' self-identity and the overall family identity is also affected. The goal of this study was to provide a better understanding of changes in self-identity and family identity for mothers who have a child or adolescent with an ABI. For this study, I recruited 14 mothers of a child with an ABI, and the mothers engaged in interviews and completed several short surveys. The mothers shared important information about changes in self-identity and family identity and made suggestions about how medical and rehabilitation services can better support families affected by ABIs. Findings revealed that families who are intentional about discussing changes to the family, such as role shifts or changes in routine, and expressing emotions adapt more effectively to the consequences from an ABI. Furthermore, the results suggest recommendations for rehabilitation professionals in supporting mothers and families. These include, educating the family about ABIs and involving mothers and families as part of the treatment process. Future directions for further research studies are identified as well as a discussion on best practices for clinicians.

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.

Concussions impact the cognitive abilities and emotional wellbeing of adolescents. More specifically, adolescents exhibit signs of executive dysfunction and depressive symptoms following concussion. Evidence suggests a link between cognitive performance and depressive symptoms in concussed populations; however, concussion research has focused mostly on cognitive deficits and emotional dysregulation in singularity, rather than as an integrated system. Therefore, the purpose of this thesis is to explore the clinical and biological relationship between depressive symptoms and executive dysfunction following mild traumatic brain injury (mTBI) or concussion in pediatric populations. Chapter 1 provides an overview of the literature surrounding children and youth with concussive injury as it pertains to executive dysfunction and depressive symptoms. Chapter 2 describes the clinical nature of the relationship between depressive symptoms and executive dysfunction. The results demonstrate that individuals with elevated depressive symptoms had comparable performance to individuals with normal levels of depressive symptoms on executive function scores. This included their performance on an inhibitory control task in which emotional distractors were presented. Regardless of levels of depressive symptoms, adolescents with concussive injury displayed impaired executive functioning compared to normative data, which emphasizes the importance of evaluating executive function following concussion. Chapter 3 involves the use of functional brain imaging to explore the physiological differences between adolescents with average and elevated depressive symptoms on emotion-mediated inhibitory control processes. The group as whole did not display activity in the frontostriatal regions that are associated with inhibitory control, which suggests a potential impairment in this network. Adolescents with elevated depressive symptoms displayed fewer areas of activity compared to adolescents with average levels of depressive symptoms. As a number of individuals (particularly those with elevated depressive symptoms) were injured in the occipital region of the skull, the coup-contrecoup impact may have resulted in frontal lobe injury. Faces were used to evoke emotional processing throughout the inhibitory control task. The results revealed that adolescents with elevated depressive symptoms were more likely to engage in brain regions subserving evaluative processing of social interactions. This might suggest that depressive symptoms display differences in physiology when emotional stimuli are present. These findings provide insight into the role the environment plays in contributing to the cognitive demands placed on adolescents recovering from concussion. Chapter 4 reviews the key messages derived from these results and describes their clinical relevance. This exploration may lead to a more holistic understanding of concussion and a better approach to injury management, particularly for adolescents who express higher levels of depressive symptoms following concussion. / Thesis / Master of Science (MSc)

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.

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.

Incurring high economic cost due to medical imaging modalities, there is a need for a low-cost, on site, diagnostic screening tool for the early detection of Traumatic Brain Injury (TBI). We hypothesize that patients with TBI will exhibit temporal and spatial gradient dynamics in the thermal signature on the surface of the skin, and that these dynamics reflect the inflammatory process. Hence, we implemented far-infrared (FIR) thermography using a blunt TBI rat model to analyze changes in the external, surface temperature gradient as an indication of internal inflammation. Results show a consistent increase in average surface temperature after 0.5 days of recovery post-impact. The trend in average surface temperature decreases after 1 day of recovery with a continual decline observed after a 4-day recovery. After 7 days of recovery, the average surface temperature begins to increase with a substantial surge seen 14 days post-impact. The trend appears to correlate well with the inflammatory process.

In the current study, mechanoporation-related neuronal injury as a result of mechanical loading has been studied using a multiscale approach. Injurious mechanical loads to the head induce strains in the brain tissue at the macroscale. As each length scale has its own unique morphology and heterogeneities, the strains have been scaled down from the macroscale brain tissue to the nanoscale neuronal components that result in mechanoporation of the neuronal membrane, while relevant neuronal membrane mechanoporation-related damage criteria have been scaled up to the macroscale. To achieve this, first, damage evolution equations has been developed and calibrated to molecular dynamics simulations of a representative neuronal membrane at the nanoscale. These damage evolution equations are strain rate and strain state dependent. The resulting damage evolution model has been combined with Nernst-Planck diffusion equations to analytically compare to intracellular ion concentration disruption through mechanical loading of in vitro neuron cell culture and found to agree well. Then, these damage evolution equations have been scaled up to the microscale for dynamic simulations of 3-dimensional reconstructed neurons of similar mechanical loads. It was found that the neuronal orientation significantly affects average damage accumulation on the neuron, while the morphology of neurons, for a given neuron type, had little effect on the average damage accumulation. At the mesoscale, finite element simulations of geometrical complexities of sulci and gyri, and the structural complexities of the gray and white matter and CSF on stress localization were studied. It was found that the brain convolutions, sulci, and gyri, along with the effects of impedance mismatch between the cerebrospinal fluid (CSF) and brain tissue localized shear stresses, at the depths of the sulcus end (near field effects) and in-between sulci (far field effects), that correlated well with the regions of tau protein accumulation that is observed in chronic traumatic encephalopathy (CTE). Further, sulcus length and orientation, with respect to impending stress waves, had a significant impact on the magnitude of stress localization in the brain tissue. Lastly, gray-white matter differentiation, pia matter, and brain-CSF interface interaction properties had minimal impact of the shear stress localization trends observed in these simulations.

Due to traumatic brain injury (TBI), numerous studies have focused on comprehensively determining the mechanical properties of the brain. This study examined the strain rate dependence of porcine brain under compression, and the microstructural damage was quantified using a confocal microscope and graphical user interface (GUI). The selected strain rates were 0.10 s-1, 0.025 s-1, and 0.00625 s-1 while the strain levels targeted for confocal imaging were 15%, 30%, and 40%. This study also characterized the stress-state dependence at a strain rate and strain level of 0.10 s-1 and 40%, respectively, under compression, tension, and shear. Strain rate dependency data exhibited viscoelastic behavior, and the analysis parameters correlated with increasing strain rate and strain level. Stress-state dependency data demonstrated distinct nonlinear behavior, and disparities were observed in the analysis parameters between different testing modes. Finite element procedures can implement this supplementary data for devising more realistic models.