Thesis (Ph. D.)--University of Missouri-Columbia, 2002. / Typescript. Vita. Includes bibliographical references (leaves 66-76). Also available on the Internet.

Thesis (Ph. D.)--University of California, San Diego and San Diego State University, 1999. / Vita. Includes bibliographical references (leaves 209-234).

Thesis (Ph. D.)--University of California, Santa Cruz, 1996. / Typescript. Includes bibliographical references (leaves 57-61).

Thesis (Ph. D.)--Drexel University, 2007. / Includes abstract and vita. Includes bibliographical references (leaves 130-141).

Thesis (PH. D.)--University of Iowa, 2007. / Supervisor: Antoine Bechara. Includes bibliographical references (leaves 174-195).

Efficient search benefits from persistent exposure to the statistical liklihoods that underpin object locations, such that time and energy expenditure tends be minimal. Inspections are made towards areas where objects are most likely to appear or have previously produced successful results. Experimentally, this phenomena has been named the ‘probability cueing effect’, and has predominantly been studied using visual search paradigms. In this context, participants bias their search towards locations where a target frequently appears, but they do not express any conscious awareness of doing so. However, in real-world tasks, it is much harder for spatial inferences to be made, with additional factors to be considered, such as consistency in where search is inititated. When the cue is learnt, it is instead consciously acknowledged. The research within this Thesis investigated search in an additional context: virtual, representational space. Probability cueing was successful but only when the environment was of minimal immersion. Parallel to visual search, participants did not express an awareness of the cue suggesting that physical movement is important for conscious awareness of learning. The transfer of probability cueing across virtual to real space was also examined, although an effect was not established. This finding has important applied implications, when considering that virtual environments are used throughout many industries as training tools. To conclude, three experiments investigated the underlying neural system that may support probability cueing, specifically the right parietal cortex. Much research has shown that this area plays a key role in allocating spatial attention across hemifields, but its input for probability cueing has not yet been investigated. These experiments used transcranial anodal (excitatory) and cathodal (inhibitory) stimulation to moduate this brain area. In a visual, 2D task and a 3D virtual environment task, search efficiency was modulated, with both stimulation types improving general search profiles. In a real-world task, search efficiency was again modulated, as well as probability cueing with stimulation interacting with the high-probability hemispace. Together these studies provide a comprehensive understanding of probability cueing under various environmental search constraints, and the role of the right parietal cortex in the guidance of this search strategy.

In a series of 6 experiments this thesis aimed to explore how the processing of peri-personal space might be affected by changes in sensory information. Previous research has shown that when stimuli is presented within peri-personal space it is processed differently, specifically it has been suggested that there is a prioritisation of space to the area around the hands. If there is a change in processing for the space around us, how might this be affected when interacting with a virtual or augmented environment in which sensory information may be altered? To investigate these changes the MIRAGE mediated reality system was used in which a live video recording of the hand is displayed in real-time in its spatially veridical location, and allows the manipulation of this image and sensory modalities separately. This allowed a more detailed evaluation of previous theories by testing spatial, temporal, and fidelity changes to the hand. Results showed spatial changes between seen and felt hand positions to significantly alter the processing of stimuli presented near and far from the hands. Specifically it was illustrated that a gradual separation between the visual and real hand locations seemed to first create an expansion in the visual receptive fields of bimodal visual-tactile neurons, and second, suggested a remapping of the limbs location to somewhere between the separate representations. Furthermore the application of transcranial direct current stimulation (tDCS), specifically cathodal stimulation, appears to have disrupted proprioceptive feedback, however these effects require further investigation and replication. Results also showed how temporal lag can impair performance on a movement task, while changes in hand fidelity did not significantly alter the processing of peri-personal space. In summary, the experiments presented in this thesis illustrate that spatial changes between seen and felt hand positions significantly alter the way we process space around the hands, and suggest that previous theories need to be re-evaluated and possibly combined to better represent how these changes occur. The findings also have implications for which factors may be most important when exploring how we process peri-personal space in an augmented or virtual environment.

Cognitive fatigue (CF) presents a considerable challenge for individuals with multiple sclerosis (MS) often negatively impacting quality of life. CF can be defined as a decrease in, or inability to sustain, optimal task performance throughout the duration of a continuous cognitive task. The following dissertation presents three original research reports which evaluate CF in MS in three distinct ways using a multidimensional approach. The objective of this dissertation was to comprehensively evaluate and quantify this frequently misunderstood symptom of the disease. The first report examines four theoretical models of CF in MS which evaluate the interrelatedness of disease severity, fatigue, depression, and sleep quality in order to determine their predictive roles with regard to CF. The second report assesses CF longitudinally by examining whether or not the ability to perform optimally on a continuous cognitive task changes as the disease progresses across a three-year time interval. The final report objectively quantifies CF in MS by evaluating changes in global and regional cerebral blood flow during a task of sustained attention using arterial spin labeling perfusion fMRI. Results of all three reports are further discussed in terms of clinical and research implications. CF is a symptom of MS not readily apparent to outside observers but presents a very real burden for people with the disease that negatively impacts their ability to lead active and productive lives. These individuals may be discriminated against because CF has thus far been a largely unverifiable subjective experience. The totality of these three studies allows for a multidimensional quantification of CF. By providing objective support to the self-reports of individuals with MS, not only can they achieve much needed validation, but this can also lead to interventions that may provide further direct benefit to their health-related quality of life.

Medio-lateral narrowing (convergence) and anterior-posterior elongation (extension) are two of the most important cell movements of the gastrulation period leading to the formation of embryonic body axis. In vertebrates, convergence and extension (CE) cell movements are regulated by the non-canonical Wnt/Planar cell polarity (PCP) signalling pathway which requires the activation of its downstream effectors, Rho GTPases. DEF6 and SWAP70 are guanine nucleotide exchange factors (GEFs) catalysing the activation of Rho GTPases to regulate the re-arrangement of actin cytoskeleton, cell polarity and cell movements. Although it has been shown that the zebrafish orthologous, Def6a and Swap70b, act downstream of Wnt5b or Wnt11 signalling pathway, respectively, regulating the CE cell movements during gastrulation, little is known about the underlying molecular mechanisms and direct downstream targets of Def6a and Swap70b. To further elucidate the function of def6a and swap70b within the non-canonical Wnt/PCP signalling pathway, Transcription Activator-Like Effector Nucleases (TALENs)-induced mutagenesis was employed to establish knock-out mutant lines lacking either def6a (qmc811), swap70b (qmc809) or both (qmc813). Phenotypic and whole-mount in situ hybridisation analyses have revealed that the anterior movement and the convergence of the lateral mesendodermal and ectodermal cells were severely impaired in def6a and/or swap70b-deficient zebrafish embryos, indicating that def6a and swap70b are required for normal CE cell movements during gastrulation. Ectopic expression of Cdc42 GTPase robustly rescued the CE cell movement defects in both def6aqmc811/qmc811 and swap70bqmc809/qmc809 homozygous mutant lines whereas ectopic expression of RacI robustly rescued CE cell movement defects only in swap70bqmc809/qmc809 homozygous mutant line, suggesting that Def6a and Swap70b acts upstream of Cdc42 and Cdc42/RacI respectively. Elevated expression of wnt5b and wnt11 detected in the mutant lines indicated that abrogation of def6a and swap70b functions interfered with Cdc42/RacI-mediated Jnk activation that negatively regulates expression of wnt11 and perhaps wnt5b. In adult def6a and/or swap70b-deficient fish, a decreased number of myeloid population was observed, suggesting that both proteins are required for balanced cell differentiation during haematopoiesis. Generation of the double homozygous mutant line revealed that def6a and swap70b act in a partially redundant manner during zebrafish embryogenesis and in a non-redundant manner during haematopoiesis. DEF6 is highly expressed in T cells and plays an immunoregulatory role in cell polarity-induced immunological synapse (IS) formation, T cell receptor (TCR) signalling, T cell activation, differentiation and inflammatory responses. Recently, it has been shown that DEF6 may also be involved in the mRNA surveillance and translation. However, the molecular mechanisms that it may be involved in and its interactors in T cells are still unknown. Hence, a novel method, BioID, which enables the promiscuous biotinylation of proximal and interacting proteins of a target protein in mammalian cells, was adapted to identify DEF6 interactome in Jurkat T cells. Notably, in vivo BioID-DEF6 fusions yielded 127 clusters of interacting and vicinal proteins, including 2 known binding partners, Rac2 and PKC and 1 known close proximity partner, PABP. GO-term classification of the identified proteins showed that the proteins are enriched not only in actin cytoskeleton organisation and mRNA translation, but also in transcription, mRNA splicing/processing, protein folding/modification and metabolic processes. Co-localisation of DEF6 with Coronin1A (CORO1A), an actin cytoskeleton regulator during IS formation, in resting and activated cells provided proof of principle for the interactome analysis suggesting that DEF6 is a multifunctional protein involved in the regulation of cytoskeletal organisation, transcription, mRNA splicing, protein folding/processing and metabolic processes.

In children with confirmed brain damage, neuropsychological research has established that evidence of lateralized (right or left hand) impairment on fine motor tests can be used to help infer dysfunction of the contralateral (opposite) cerebral hemisphere and its associated cognitive skills (e.g., verbal and visuospatial skills). In neuropsychological assessments of children with subjected brain dysfunction (such as learning disabilities and/or attention-deficit hyperactivity disorder), fine motor tests are often used for much the same purpose. This constitutes an example of what is referred to in neuropsychology as the "Comparison of the Left and Right Sides of the Body" inferential method. However, its use for children with suspected brain dysfunction is not supported by the existing research literature. Furthermore, a recent series of studies on children with left hand motor impairment ("extreme right-handers") and no confirmed brain damage has produced results which are inconsistent with those that would be predicted based on traditional neuropsychological theory. It appears possible that previous studies found little relationship between lateralized motor impairment and distinctive cognitive deficits in children with suspected brain dysfunction largely due to the specific motor tests that they used (i.e., ones that rely more heavily on visuospatial/right hemisphere skills than verbal/left hemisphere skills). The Name Printing Test (Joschko & Bailey, 1996) was proposed to be a motor test that involves the skills of both cerebral hemispheres. It was therefore hypothesized to account for a significant amount of unique variance in performance on measures of both verbal and visuospatial cognitive skill, above and beyond that accounted for by the Grooved Pegboard and Finger Tapping Tests, in a sample of 77 right-handed children with suspected brain dysfunction. Left hand motor test scores were hypothesized to account for the greatest amount of variance in visuospatial cognitive skill, while right hand scores were hypothesized to account for the greatest amount of variance in verbal cognitive skill. The WlSC-III Verbal Comprehension and Perceptual Organization 6ctor scores were used as the measures of verbal and visuospatial cognitive skill, respectively. Hierarchical multiple regression was the primary method of analysis used to test the research hypotheses. The results provided little support for these hypotheses. Specifically, right and left hand motor test scores were found to be about equal in predicting verbal and visuospatial cognitive skills. Furthermore, only Grooved Pegboard scores accounted for a significant amount of unique variance in visuospatial cognitive skill, while no motor test score was a significant predictor of verbal cognitive ability. Little support was found for the use of the "Comparison of the Left and Right Sides of the Body" inferential method in this clinical group, and it was suggested that such methods of inference require more extensive validation. The Name Printing Test and Grooved Pegboard were found to be sensitive indicators of psychomotor impairment in children with suspected brain dysfunction, while the Finger Tapping Test was not. / Graduate