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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

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Articular cartilage has limited intrinsic healing capacity due to its dense and avascular structure. Clinical approaches have been developed to address the limitations associated with the poor ability of articular cartilage to regenerate. Current clinically approved techniques, however, can result in repair tissue that lacks appropriate hyaline cartilage biochemical and biomechanical properties, which lead to uncertain long-term clinical outcomes. Using tissue engineering strategies and a range of scaffolding materials, cell types, growth factors, culture conditions, and culture times, engineered tissues have been produced with compositional and biomechanical properties that approximate that of native tissue. In these studies, a considerable number of samples are typically sacrificed to evaluate compositional and mechanical properties, such as the amount of deposited collagen and sulfated glycosaminoglycan (sGAG) in the constructs. The number of sacrificed samples, as well as the amount of time and resources spent to evaluate the sacrificed samples using current gold standards, motivates an alternative method for evaluation of compositional properties. Vibrational spectroscopy, including infrared, has been considered as an alternative technique for assessment of tissues over the last 15-20 years. Infrared spectroscopy is based on absorbance of infrared light by tissue functional groups at specific vibrational frequencies, and thus, no external contrast is required. Vibrational spectroscopy is typically performed in two frequency regions, the mid infrared region (750-4000 cm-1), where penetration depth is limited to approximately 10 microns, and the near infrared (NIR) region (4000-12000 cm-1). In the NIR region, penetration of light is on the order of millimeters or centimeters, which makes it ideal for obtaining data through the full depth of engineered constructs. Here we employ NIR spectroscopy to nondestructively monitor the development of tissue-engineered constructs over culture period. / Bioengineering

The Anthropocene epoch in which we are currently living, also known as the Holocene, has brought about unprecedented losses in planet Earth’s biodiversity. Numerous extirpations of floral and faunal species have been influenced by human encroachment and more specifically, the exploitation of such species and the respective habitats in which they reside. It is this notion that has propelled many scientists to take up intellectual arms in an effort to protect these invaluable resources. The purpose of this research was to develop technologies to measure and evaluate various variables that influence animal physiology, specifically in amphibians who represent the most threatened class of all animal taxa. Species-specific knowledge including life history and an understanding of evolutionary traits are often needed to effectively guide the management decisions surrounding any given animal population. Specific objectives of this project were to develop non-invasive methods, such as hormone monitoring, machine learning-aided ultrasonography, and near-infrared spectroscopy (NIRS), to assess vital physiological traits, such as biological sex, reproductive status, and chytrid fungus pathogen detection in threatened amphibian species. The novel technologies developed and applied in amphibians here may provide insights for addressing conservation related questions in other animal as well as plant species. Additionally, automation of physiological monitoring techniques through the use of machine learning methods reduces barrier to entry and enables these technologies to be operated by a larger practitioner base. This research also serves to advance methods surrounding chemometric analyses as it pertains to the discipline of wildlife spectroscopy, where large multivariate datasets require data manipulation strategies to produce robust prediction models for the physiological trait of interest for qualitative or quantitative assessment. To that end, a multi-model framework is provided for optimizing predictive outcomes to address questions relating to wildlife management and conservation initiatives.

Unwanted and distressing visual imagery is a persistent and emotionally taxing symptom characteristic of several mental illnesses, including depression, schizophrenia, and posttraumatic stress disorder. Intrusive imagery symptoms have been linked to maladaptive memory formation, abnormal visual cortical activity during viewing, gaze pattern deficits, and trait characteristics of mental imagery. Emotional valence of visual stimuli has been shown to alter perceptual processes that influence the direction of attention to visual information, which may result in enhanced attention to suboptimal and generalizable visual properties. This study tested the hypothesis that aberrant gaze patterns to central and peripheral image regions influence the formation of decontextualized visual details which may facilitate involuntary and emotionally negative mental imagery experiences following a stressful or traumatic event. Gaze patterns and hemodynamic response from occipital cortical locations were recorded while healthy participants (N = 39) viewed and imagined scenes with negative or neutral emotional valence. Self-report behavioral assessments of baseline vividness of visual imagery and various cognitive factors were combined with these physiological measures to investigate the potential relationship between visual perception and mental recreation of negative scenes. Results revealed significant effects of task and valence conditions on specific fixation measures and hemodynamic response patterns in ventral visual areas, which interacted with cognitive factors such as imagery vividness and familiarity. Findings further suggest that behaviors observed during mental imagery reveal processes related to representational formation over and above perceptual performance and may be applied to the study of disorders such as PTSD. / Ph. D. / Intrusive imagery describes the visual components of flashbacks that are common to mental disorders such as posttraumatic stress disorder (PTSD), obsessive-compulsive disorder, and schizophrenia. Several explanations for this symptom have been suggested, including incomplete memories, changes in visual brain structures and function, inappropriate viewing patterns, and an individual’s ability to imagine visual scenes in detail. The emotional tone of a scene has also been shown to affect viewing patterns, which may lead to attention being narrowly directed toward specific visual details while ignoring surrounding information. This study tested whether inappropriate viewing patterns to central and outer image regions in negative images influence narrow focus to emotional details, thereby allowing flashback-type imagery to occur following a traumatic or stressful event. Viewing patterns and blood flow in brain regions were measured while participants (<i>N</i> = 39) viewed and imagined scenes with negative or neutral emotional tone. Self-reported detail of voluntary mental imagery and other cognitive factors such as content familiarity and pleasantness were used to investigate a relationship between viewing and imagery of emotionally negative scenes. Results showed that certain cognitive factors as well as the type of visual task significantly affected particular eye movements and patterns of blood flow in visual regions of the brain. These measures interacted with cognitive factors such as imagery detail and content familiarity. Findings further suggest that behaviors observed during mental imagery reveal cognitive processes over and above those during viewing and may be useful in the study of disorders such as PTSD.

Master of Science / Department of Kinesiology / Thomas J. Barstow / Near infrared spectroscopy is currently routinely used to assess tissue (muscle) oxygenation at rest and during exercise. While most investigators assume that hemoglobin ([Hb]) is the major contributor to the responses seen during exercise, the relative contribution of myoglobin ([Mb]) to the NIRS signals remains controversial. PURPOSE: a) To calculate the range of light absorbing potential (LAP) of hemoglobin and myoglobin in mammalian skeletal muscle at rest based on analysis of published chemical and morphometric data in humans and other mammals (Part 1), and b) use the information in a) to interpret changes in total [Hb+Mb] from NIRS during exercise (Part 2). METHODS: Part 1: Information was retrieved from five published studies with regard to capillary density (#caps/mm2) and [Mb] in skeletal muscle of human, horse and rat. Preference was given to studies in which both measurements were provided for the same muscles. [Hb] in skeletal muscle was estimated as a function of capillary density, [Hb] in systemic blood, and the ratio of capillary-to-systemic hematocrit at rest and during exercise. Part 2: Changes in total [Hb] + [Mb] (as t[Hb+Mb]) from published NIRS data obtained from human subjects performing cycling or knee extension exercise were interpreted in the context of the results of Part 1. RESULTS: Part 1: Individual group mean values for skeletal muscle [Mb] in the literature ranged from 0.25-0.67 mM in human samples, with a similar range for muscles of the rat hindlimb; horse limb muscles tended to be higher (up to 1.0 mM). Capillary densities ranged from ~200 to 600 caps/mm2 in human and rat muscles, and up to 800 caps/mm2 in horse muscle. Assuming a resting capillary hematocrit of 22% and 4 fold greater LAP for each mole [Hb] vs [Mb], the resulting estimation of capillary [Hb] ranged from ~0.03 to 0.09 mM in human and rat muscles, and up to ~0.13 mM in horse muscles. The results suggest that [Mb] could contribute ~50-70% of the total LAP at rest in human skeletal muscle. Part 2: With exercise, total heme by NIRS can increase ≥ 30% in individual human subjects. Assuming this increase reflects only increased [Hb], this fits well with the observed increase in capillary hematocrit with exercise. CONCLUSIONS: 1) In skeletal muscle at rest, [Mb] is likely to be at least as significant a light absorbing heme as is [Hb] in most mammalian muscles, including the human leg. 2) Observed increases in t[Hb+Mb] with NIRS during exercise can be explained by an increase in capillary hematocrit, even in the presence of significant [Mb].

Master of Science / Department of Diagnostic Medicine/Pathobiology / Larry C. Hollis / Mark F. Spire / Two studies were undertaken to evaluate the use of Near Infrared Spectroscopy (NIRS) to determine arterial oxygen saturation (StO[subscript]2) in cattle with naturally-occurring Undifferentiated Bovine Respiratory Disease (UBRD) and experimentally-induced UBRD utilizing Mannheimia haemolytica. The first study was a natural infection model utilizing 679 beef heifers weighing approximately 227 kg (500 pounds) originating from a southeastern U.S. salebarn. Heifers were evaluated for UBRD upon feedlot arrival, at revaccination, at day 35 on feed, at re-implant time, and two weeks prior to shipment for slaughter. Animals deemed to have UBRD were treated for UBRD and data was collected for 5 days following treatment, while a comparable healthy cohort was also evaluated at the time of treatment. There was a trend for NIRS to be able to predict the incidence of subsequent UBRD when cattle were evaluated on arrival (p=0.0552). However, the ability to detect UBRD in clinically ill cattle was not significantly different (p>0.1690) when compared to healthy cohorts in this model. When carcass characteristics were evaluated at each time point, NIRS StO[subscript]2 values were able to differentiate between yield grades of animals with UBRD and healthy cohorts when evaluated at revaccination, day 35, re-implant, and pre-shipping (p<0.0199). NIRS tended to be able to differentiate yield grades at initial processing (p=0.0513). StO[subscript]2 was not a predictor of quality grade at any time point (p>0.1023), nor was there any correlation between lung lesions at slaughter and StO[subscript]2 (p>0.2292). The second study involved 12 head of 181 kg (400 pound) heifers which were subjected to an experimental challenge model of Mannheimia haemolytica. Animals were evaluated daily and StO[subscript]2 readings recorded 12 hours pre-inoculation, at inoculation, 6, 12 and 24 hours post inoculation and daily for the next 12 days. While NIRS could not definitively differentiate healthy cohort cattle from challenge cattle (p>0.0713), there were trends toward challenge cattle having lower StO[subscript]2 values than healthy controls. The authors conclude that while these studies did not provide conclusive evidence of the ability of NIRS to detect UBRD, further studies with a machine that is specifically calibrated and designed for use with cattle should be performed.

Children and adolescents are thought to use oxidative metabolism to a greater extent than adults during high intensity exercise. The studies reported in this thesis examine the nature and implications of age-related differences in muscle metabolism during high intensity exercise and recovery. Chapter 4 concluded that during heavy intensity exercise, phosphocreatine (PCr) kinetics did not differ with age or sex, while Chapter 5 revealed that during very heavy intensity exercise, the fundamental τ was slower and slow component amplitude greater in men compared with adolescent boys, indicating that exercise intensity might play a role in determining age-related differences in muscle metabolism. In Chapter 6, two bouts of very heavy intensity exercise were completed, and prior exercise reduced the PCr slow component amplitude in men but not boys. Deoxyhaemoglobin (HHb) kinetics was faster in adolescents compared with adults during both heavy and very heavy intensity exercise, indicating that matching of oxygen delivery to oxygen utilisation is less precise at the onset of exercise in adolescents compared with adults. PCr recovery from high intensity exercise was faster in boys than men, but not different in girls and women, as described in Chapter 7. The speed of PCr recovery was correlated with maturity in adolescents, but was not correlated with end-exercise [PCr] or pH. Two different tests to measure mitochondrial capacity in adolescents were evaluated in Chapter 8, and a fitted curve and gated test were both used to determine PCr recovery kinetics. Finally, in Chapter 9, age-related differences in muscle metabolism and oxygenation during fatiguing exercise were examined; a strong trend for greater fatigue in adults compared with adolescents was accompanied by greater metabolic perturbation in adults. Overall, these data show that muscle metabolism and oxygenation differs between adolescents and adults during and following very high intensity exercise.

Variability in neural activity has historically been treated as noise, in favour of deriving estimates based on central tendency (e.g., mean). Recently, researchers have shown that variability and mean confer different sources of information and that increased variability in neural activity is associated with superior behavioural performance and that it decreases during late-life. Although mounting evidence suggests that neural variability is beneficial, it is less clear whether these findings are driven by within- or between-person factors and whether they are apparent during higher-order cognitive tasks. Further, variability can be derived in several different ways, drawing into question its congruence across operationalizations. The present investigation sought to separate within- and between-person sources of variance in order to ascertain what was driving any observable effects in three operationalizations of cerebral oxygenation, computed based on central tendency (mean), variability (standard deviation) and signal complexity (multivariate multiscale entropy). 25 older adults (71-81 years of age) completed two tasks of executive functions while undergoing assessment using functional near infrared spectroscopy. Time-varying covariation models were employed to estimate the effects of cerebral oxygenation on behavioural performance, as well as the moderating effects of age and fall status. Findings suggest that mean and variability are differentially associated with behavioural performance and are increased in older adults at greater fall risk. Whereas mean based computations were positively associated with more accurate and faster responding, variability based computations were primarily associated with faster responding only and occurred in non-overlapping regions of prefrontal cortex. Future studies of neural variability may consider examining within- and between-person factors and operationalizing signal complexity in cerebral oxygenation over longer time periods to examine its effects over multiple time scales. / Graduate / drewh@uvic.ca