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Since the development of magnetic resonance imaging (MRI), there have been many novel advances in our understanding of brain structure and function. More recently, functional MRI has revealed networks of spatially isolated brain regions with temporally correlated activity, forming resting state networks. Research has long shown that mindfulness can produce psychological improvements. A new wave of research is demonstrating how mindfulness is associated with alterations in these brain networks. The current thesis examined changes in patterns of functional connectivity associated with scores from a commonly used mindfulness questionnaire in three resting state networks: the default mode network, the central executive network, and the salience network. Independent component analysis data from 32 healthy participants revealed that mindfulness is associated with altered patterns of functional connectivity in all three networks. For example, decreased connectivity was observed in the precuneus in two of the networks, a region associated with mind wandering. This suggests that mindfulness has a physiological influence on the resting state functional connectivity of the brain that coincides with the underlying principles of mindfulness. / May 2017

This thesis is a study of the act of traveling in its pure form: as a journey between two points; it is an act that requires both a point of origin and a point of destination. Yet, this study is not concerned with the logistics of either. Rather, it depends only upon the existence of these two locations as limits of both space and time between which exists a transient environment. Complimentary to the constant movement embodied in the act of travel, the act of pausing and resting is fundamental to fulfilling a biological need that arises from the exhaustion that accompanies continuous movement. The modern highway rest area was selected as this thesis project because of its nature as neither a permanent origin nor destination of transit. It currently exists as an oft forgotten building type in architectural design, despite its significant role in the commonplace activity of transit. This project seeks to provide the programmatic functions that satisfy these fundamental needs while engaging the nature of the building typology as a threshold through which the traveler passes. The architectural and structural expression and detailing are based upon the inherently rhythmic nature of the act of vehicular travel and are intended to reflect the changes in rates of movement that aid in the transition from moving to pausing. Thus, the average rates of movement embodied in various modes of mobility throughout the building inform the architectural decisions that aid in the choreographed movement into, through, and out of the design. / Master of Architecture

Clinical care for major depressive disorder (MDD) would be greatly improved if we had reliable clinical predictors of individual antidepressant treatment outcome. While, at the present time, no biomarkers have sufficiently proven utility to be ready for clinical application, several neuroimaging modalities have shown promise for such development. Attempts to combine the recently developed modality of resting-state functional Magnetic Resonance Imaging (rs-fMRI) with pharmacological challenges to explore the impact of antidepressants on resting-state brain connectivity have just begun (McCabe et al., 2011a, McCabe et al., 2011b). The aim of the current study was to investigate the effects of a single dose of the SSRI (selective serotonin reuptake inhibitor) escitalopram on resting-state functional connectivity in health.

The aim of this thesis was to describe the relationships between energy expenditure and body composition in healthy adults and children and in patients with metabolic disorders. In a healthy population resting energy expenditure (REE) is highly influenced by body composition, specifically lean mass (LM). Prediction equations can therefore accurately predict REE from body composition in healthy individuals. However, application of these equations to clinical patients, in whom metabolism is disordered, risks miscalculation of energy metabolism due to their dissociation between body composition and energy expenditure. Therefore new prediction equations were derived based on precise body composition measurements in healthy adults and children. Then, in patients with metabolic disorders, differences between their measured and equation-predicted REE and LM were presented as standardised Z scores. REE in healthy adults was predicted by the coefficients: age, fat mass and fat-free mass. LM in healthy adults was predicted by the coefficients: bone mineral content and height2 in men; and by fat and height2 in women. In healthy children, REE was predicted using gender specific models: by fat and LM in boys; and by solely LM in girls. REE and LM were then measured in adult and paediatric patients with metabolic disorders (Lipodystrophy, Thyrotoxicosis and Resistance to Thyroid Hormone β or α), and Z scores were calculated to highlight their deviations from the healthy populations. In adults, thyrotoxicosis patients displayed the highest REE Z scores (5.8), followed by lipodystrophy (2.9) and RTHβ cases (1.8), with RTHα demonstrating the lowest REE Z scores (-2.3). For LM, lipodystrophy patients exhibited with the highest Z scores (4.2), followed by RTHα patients (2.1), with RTHβ patients showing normal LM Z scores (-0.2) and thyrotoxicosis patients presenting with the lowest LM Z scores (-1.2). In the paediatric patients, RTHβ patients demonstrated REE Z scores similar to healthy controls (males; -0.15, females; 0.15), but RTHα patients displayed lower REE Z scores (male; -0.82, female; -2.2) compared to RTHβ patients and healthy controls. These studies highlight the disassociation between REE and body composition in patients with metabolic disorders. The application of a prediction equation for REE to calculate Z scores between measured and predicted values allows quantification of the differences between patients with metabolic disorders and healthy populations, and is a new and important concept.

Schizophrenia (SCZ) is a complex psychiatric disorder including various symptoms. Resting-state fMRI investigations mostly focused on functional connectivity alterations in SCZ reflecting the spontaneous activity’s spatial structure. Complementing its spatial structure, the brain’s spontaneous activity can be characterized by a complex temporal structure such as scale-free dynamics or long- range temporal correlations (LRTCs). However, it remains an open question whether the temporal structure of spontaneous brain activity, as indexed by the power-law exponent (PLE), can provide biomarkers specific to SCZ as distinguished from other psychiatric disorders like major depressive disorder (MDD) and bipolar disorder (BP). Here, we studied a large-scale cohort (n = 244) of two independent schizophrenic data sets (n = 45), MDD (n = 28), and BP patients (n = 73, in manic, depressed, and euthymic phases) and 98 healthy controls. We found significant PLE reduction in specifically the medial prefrontal cortex (mPFC) in SCZ. This was replicated in an independent sample and was shown to be specific when compared to MDD and different phases of BP. Due to its disease-specific nature, the mPFC PLE reduction may eventually serve as a biomarker for SCZ.

Background: There is growing evidence of abnormalities in neurocognition, neuroanatomy, and functional connectivity in posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). However, there has been less work on individuals who suffer with comorbid PTSD and MDD. It is important to investigate the neurobiology of this overlap because of its prevalence, its associated morbidity, and the hope that it may shed more light on the mechanisms involved in each disorder, including the role of the prefrontal regions. This dissertation tests the hypothesis that women with PTSD and MDD display distinct patterns of neurocognitive impairment and associated brain dysfunction, relative to healthy controls, and these effects will be amplified in patients with both disorders. Methods: This dissertation was undertaken within the Drakenstein Child Health Study, a study exploring child health determinants in mother-infant dyads from the Drakenstein district, Western Cape. Mothers (between 18 and 50 years) were recruited and divided into 4 groups: PTSD, MDD, PTSD with MDD, and healthy controls. Participants were assessed using the computerised NIH Toolbox, and paper and pencil neurocognitive tests. Domains assessed included memory, learning, and processing speed, and with particular focus on executive function and attention domains. Participants underwent resting-state functional imaging as well as structural brain imaging. Functional connectivity within and between cognitive control networks (salience network, dorsal attention network, and frontoparietal networks) and a default mode network were compared across the 4 groups. Neuroanatomical indices (cortical thickness, volume, and surface area) of 10 frontal cortical regions from the Desikan-Killiany atlas in Freesurfer 6 were analysed across the 4 groups. Results: All three clinical groups demonstrated no group differences on measures of attention and executive function, diagnoses of PTSD and MDD were associated with more intrusive thoughts and delayed recall impairment, respectively. However, neurocognitive findings indicate that PTSD with comorbid MDD is not associated with greater neurocognitive dysfunction relative to mono-diagnostic groups. Abnormal resting-state connectivity was observed for the MDD group in the default mode network, and for both comorbid and MDD patient groups within frontoparietal networks. Abnormal salience network connectivity for the comorbid group was observed when examining performance on the Pattern Comparison Processing Speed test. No between-network connectivity group differences were observed. Surface area and volume reductions of prefrontal regions were evident for PTSD and MDD, however, no volumetric and surface area differences were observed for the comorbid group. Conclusion: In this sample of mothers from a low-middle income region, distinct patterns of neurocognitive dysfunction and impairment in PTSD, MDD, and PTSD with MDD were observed. However, contrary to hypotheses, comorbidity is not associated with greater dysfunction and impairment and the associations of PTSD and comorbid MDD are not amplified in this sample. These findings have implications for the development of treatment plans for patients diagnosed with PTSD, MDD, and PTSD with comorbid MDD, so that interventions are tailored in a way that is responsive to differences between these groups in the presentation of neurocognitive profile, brain function, and structure.

Indiana University-Purdue University Indianapolis (IUPUI) / Negative urgency, defined as a tendency to act rashly under extreme negative emotion, is strongly associated with tobacco use. Despite the robust cross-sectional and experimental evidence linking negative urgency and tobacco use, neural correlates of negative urgency in tobacco use have not been studied. The purpose of the current study was to 1) identify neural circuits that differ between tobacco users and non-tobacco users and 2) explore the relationship between resting-state seed-based functional connectivity (rsFC) and negative urgency, both in the overall group and between tobacco users and non-tobacco users. Using negative urgency-related brain regions as seed regions (voxel level p = .005, cluster-level a < .05), compared to non-tobacco users (n = 21; mean age = 36.57, 62% female, 76% white), tobacco users (n = 22; mean age = 37.50, 64% female, 77% white) had stronger rsFC strengths in the right amygdala – left medial orbitofrontal cortex/ventromedial prefrontal cortex circuit and the right nucleus accumbens – right temporoparietal junction circuit. Additionally, rsFC in the bilateral temporal pole – left supramarginal gyrus circuits was positively correlated with negative urgency (Left temporal pole: r = .55, p < .001; Right temporal pole: r = .51, p < .001). The current study extends previous neuroimaging findings, which have mainly focused on how negative urgency is related to brain responses in localized, segregated brain regions, by examining the network-level interactions between different brain regions. This study provides prime preliminary data for future neuroimaging studies of negative urgency by providing potential target networks that would aid the development of novel intervention strategies for negative urgency-based maladaptive behaviors.

The effects of either 12-wk of high-intensity endurance or resistance training on resting metabolic rate (RMR) were investigated in 47 males aged 18-35 y. Subjects were randomly assigned to either a control (C), resistance- trained (RT) or endurance-trained (ET) group. After training both exercise groups showed significant declines in relative body fat either by reducing their total fat weight and maintaining fat-free weight (ET) or by reducing their total fat weight and increasing fat-free weight (RT). RMR did not significantly change after either training regimen although a small decline in energy intake was observed along with an increase in energy expenditure [ET, 2.721 MJ (650 kcal) per training day]. These results suggest that both endurance and resistance training may help to prevent an attenuation in RMR normally observed during extended periods of negative energy balance (energy intake < expenditure) by either preserving or increasing a person's fat-free weight.

A cross-sectional study was designed to determine the relationship between aerobic fitness and resting metabolic rate (RMR) in 69 males exhibiting a wide range of aerobic fitness levels (V̇O2max = 32.8-78.1 mL · kg-1 · min-1). The results of this study indicated that RMR was not significantly different between trained and untrained individuals when expressed in kJ · kg fat-free weight-1 · hr-1 or using an ANCOVA with fat-free weight as the covariate and RMR as the dependent variable (F ratio = 0.353, P < 0.70). In addition, this study also failed to support a previously suggested hypothesis that an elevated RMR may only be observed in those individuals exhibiting both high V̇O2max values and currently training a minimum of 12- 16 h/wk. Thus, the results of this study strongly suggest that RMR is independent of both a person's current aerobic level and training status.