Children born prematurely exhibit a broad range of neuroanatomical abnormalities. The aim of this study was to investigate the long-term effects of very preterm birth on brain volume (cortical and subcortical), cortical thickness and surface area. The participants were 25 children born very preterm (<32 weeks gestational age) without significant post-natal medical sequelae and 32 term-born children between 7 and 10 years of age. Neuroanatomical measures were derived from an automated pipeline. The results suggest a pattern of decreased brain volume, surface area and cortical thickness for children born preterm and the relation between subcortical gray volume and total brain volume differed between groups. The cortex was significantly thinner for children born preterm than term-born children in focal regions of the parietal and temporal lobes. Therefore, even without significant postnatal medical sequelae, very preterm children still exhibit structural differences that persist into middle childhood.

Children born prematurely exhibit a broad range of neuroanatomical abnormalities. The aim of this study was to investigate the long-term effects of very preterm birth on brain volume (cortical and subcortical), cortical thickness and surface area. The participants were 25 children born very preterm (<32 weeks gestational age) without significant post-natal medical sequelae and 32 term-born children between 7 and 10 years of age. Neuroanatomical measures were derived from an automated pipeline. The results suggest a pattern of decreased brain volume, surface area and cortical thickness for children born preterm and the relation between subcortical gray volume and total brain volume differed between groups. The cortex was significantly thinner for children born preterm than term-born children in focal regions of the parietal and temporal lobes. Therefore, even without significant postnatal medical sequelae, very preterm children still exhibit structural differences that persist into middle childhood.

Neuroscientists have uncovered much about the dorsal and ventral visual object processing pathways. However, little is understood about the functional development of these pathways in human infants. Behavioral data has shown that as early as 2.5 months, infants are sensitive to spatiotemporal information for object individuation in occlusion events. This study used Near Infrared Spectroscopy to assess neural activation (as evidenced by an increase in HbO2) in four areas of the pathways: primary visual cortex (O1), posterior parietal cortex (P3), lateral occipital (T5), and inferior temporal (T3) in awake human infants aged 5.5 months while they view either a spatiotemporaldiscontinuity event or a control event. Three major predictions were made: 1) since the events contain visually distinct objects, there should be significant neural activation in O1 to both events, 2) if the dorsal route mediates the processing of spatiotemporal discontinuities, then there should also be a significant increase in P3 in response to the spatiotemporal-discontinuity event but not to the control event, and 3) activation present in T3 and T5 should not vary by condition if the ventral pathway is not responsible for the processing of spatiotemporal discontinuities. Results supported all three predictions.

Metabolic Syndrome (MetS), the clustering of obesity, high blood pressure, and disordered glucose and lipid/lipoprotein metabolism within a single individual, is associated with poorer cognitive function and dementia in later life. It has been hypothesized that cognitive impairment in MetS occurs primarily within the context of inflammation. MetS risk factors are also associated with thinning of the cerebral cortex. However, the mechanisms by which MetS and inflammation affect the brain are poorly understood. The present study used statistical mediation to examine the relationship between MetS risk factors, cortical thickness in a priori regions of interest (ROIs) and inflammation. ROIs in the inferior frontal, superior temporal, middle frontal, supra marginal, anterior cingulate and middle occipital regions were chosen from the previous literature. Serum levels of pro-inflammatory markers (interleukin 1, interleukin 2, interleukin 6 and C-Reactive Protein) were measured using enzyme-linked immunosorbent assays. Forty-three adults between the ages of 40 and 60 years underwent a health screen, neuropsychological testing and structural magnetic resonance imaging. A higher number of MetS risk factors was associated with thinning in the inferior frontal ROI (β=-0.35, p = 0.019). A higher number of MetS risk factors was also associated with higher levels of serum interleukin 2 (β=0.31, p=0.04). A higher level of serum interleukin 2 was also associated with reduced thickness in the inferior frontal ROI (β=-0.41, p=0.013). After accounting for the effects of interleukin 2, the number of MetS risk factors was no longer associated with cortical thickness in the inferior frontal ROI indicating successful statistical mediation and pointing towards a potentially important role for imflammation in linking MetS to cortical thinning and cognitive vunlerability. / text

Brain and behavioural disorders represent a leading cause of morbidity and suffering worldwide. The 'fierce' mouse has a spontaneous deletion of Nr2e1 that results in a complex phenotype that includes cortical hypoplasia and socially abnormal behaviours. Notably, functional protein and regulatory equivalency of mouse and human NR2E1 has been established. Furthermore, human studies implicate the genomic region containing NR2E1 in mental illness, although a role for NR2E1 in humans is currently unknown. Here, I integrate mouse models and human molecular genetics to understand the involvement of NR2E1 in human brain-behaviour development. First, we test the hypothesis that the spontaneous 'fierce' deletion involves onlyNr2el. It was demonstrated that the 'fierce' mutation results in the loss of all Nr2e1 exons without affecting neighbouring genes. Next, the hypothesis that some humans with cortical malformations will harbour NR2E1 mutations was tested by sequencing the coding, untranslated, splice-site, proximal promoter, and evolutionarily conserved regions of this gene in 60 subjects with microcephaly. Four candidate regulatory mutations were identified. To help interpret these findings, the genomic architecture and molecular evolution of NR2E1 were characterized in 94ethnically-diverse humans and 13 non-human primates, which indicated strong functional constraint. Finally, the hypothesis that some humans with behavioural and psychiatric disorders will harbour mutations in NR2E1 was tested by sequencing the regions outlined above in 126humans with impulsive-aggressive disorders, bipolar disorder, or schizophrenia. Eleven candidate regulatory mutations were identified. Taken together, the findings presented in this thesis are consistent with the proposal that non-coding regulatory mutations may be important to the pathogenesis of brain-behavioural disorders in some humans.

When viewing a face, healthy individuals tend to fixate on upper regions, particularly the eyes, which provide important configural information about the spatial layout of the face. In contrast, individuals with face blindness (prosopagnosia) rely more on local features – particularly the mouth. Presented here is an examination of face perception deficits in individuals with Posterior Cortical Atrophy (PCA). PCA is a rare progressive neurodegenerative disorder that is characterized by atrophy in occipito-parietal and occipito-temporal areas. PCA primarily affects higher visual processing, while memory, reasoning, and insight remain relatively intact. Common among individuals with PCA is simultanagnosia, an inability to perceive more than one object or detail simultaneously. One might consider simultanagnosia the most extreme form of a feature-based approach. In a series of investigations, individuals with PCA and their healthy control participants completed a same/different discrimination task in which images of faces were presented as cue-target pairs. Eye-tracking equipment (Experiment 1) and the newly developed Viewing window paradigm (Experiment 2) were used to investigate scanning patterns when faces were presented in full view, and through a restricted viewing aperture, respectively. In contrast to previous prosopagnosia research, individuals with PCA each produced unique scan paths that focused on one aspect of the face. Individuals with PCA tended to focus on areas of high-contrast but many of these areas were not diagnostically useful, suggesting that they were having difficulty processing the face even at a featural level. These results suggest a role of simultanagnosia in the scan patterns of PCA patients that is not reflective of ‘typical’ prosopagnosia, and instead points to simultanagnosia, sometimes matched with basic perceptual impairments, as a significant contributor to the face perception deficits seen in PCA.

Bone is a 3D dynamic and unique tissue that structurally adapts in response to mechanical stimuli. Comparative skeletal morphology is commonly utilized to infer ancient hominins' modes of locomotion; however, instances of remarkable gross similarity despite different modes of locomotion do occur. A common cited example is the similarity between the skeletal elements of bipedal human (Homo sapiens) hands/feet and quadrupedal black bear (Ursus americanus) front/hind paws. Through novel 3D Micro-CT and 2D histomorphology analysis, this thesis tests the hypothesis that a 3D microscopic analysis of biomechanically regulated cortical bone structures provides a more representative and accurate means to infer a species' mode of locomotion. Micro-CT data were collected at the mid-diaphysis of human (n=5) and bear (n=5) third metacarpal/metatarsal pairs and compared with independent and paired t-tests, Pearson correlation coefficients and Bland-Altman plots. Bone microarchitecture is quantifiable in 3D and accessible through non-destructive Micro-CT. Interspecies variation was present, however no significant cortical differences between elements of humans and bears was found. Histological inspection revealed further variation between and within species and element. A key limitation was sample size and further investigation of the relationship between mechanical loading and mode of locomotion is warranted.

When viewing a face, healthy individuals tend to fixate on upper regions, particularly the eyes, which provide important configural information about the spatial layout of the face. In contrast, individuals with face blindness (prosopagnosia) rely more on local features – particularly the mouth. Presented here is an examination of face perception deficits in individuals with Posterior Cortical Atrophy (PCA). PCA is a rare progressive neurodegenerative disorder that is characterized by atrophy in occipito-parietal and occipito-temporal areas. PCA primarily affects higher visual processing, while memory, reasoning, and insight remain relatively intact. Common among individuals with PCA is simultanagnosia, an inability to perceive more than one object or detail simultaneously. One might consider simultanagnosia the most extreme form of a feature-based approach. In a series of investigations, individuals with PCA and their healthy control participants completed a same/different discrimination task in which images of faces were presented as cue-target pairs. Eye-tracking equipment (Experiment 1) and the newly developed Viewing window paradigm (Experiment 2) were used to investigate scanning patterns when faces were presented in full view, and through a restricted viewing aperture, respectively. In contrast to previous prosopagnosia research, individuals with PCA each produced unique scan paths that focused on one aspect of the face. Individuals with PCA tended to focus on areas of high-contrast but many of these areas were not diagnostically useful, suggesting that they were having difficulty processing the face even at a featural level. These results suggest a role of simultanagnosia in the scan patterns of PCA patients that is not reflective of ‘typical’ prosopagnosia, and instead points to simultanagnosia, sometimes matched with basic perceptual impairments, as a significant contributor to the face perception deficits seen in PCA.

Bone is a 3D dynamic and unique tissue that structurally adapts in response to mechanical stimuli. Comparative skeletal morphology is commonly utilized to infer ancient hominins' modes of locomotion; however, instances of remarkable gross similarity despite different modes of locomotion do occur. A common cited example is the similarity between the skeletal elements of bipedal human (Homo sapiens) hands/feet and quadrupedal black bear (Ursus americanus) front/hind paws. Through novel 3D Micro-CT and 2D histomorphology analysis, this thesis tests the hypothesis that a 3D microscopic analysis of biomechanically regulated cortical bone structures provides a more representative and accurate means to infer a species' mode of locomotion. Micro-CT data were collected at the mid-diaphysis of human (n=5) and bear (n=5) third metacarpal/metatarsal pairs and compared with independent and paired t-tests, Pearson correlation coefficients and Bland-Altman plots. Bone microarchitecture is quantifiable in 3D and accessible through non-destructive Micro-CT. Interspecies variation was present, however no significant cortical differences between elements of humans and bears was found. Histological inspection revealed further variation between and within species and element. A key limitation was sample size and further investigation of the relationship between mechanical loading and mode of locomotion is warranted.

Past research associated relative left frontal cortical activity with approach motivation, or the inclination to move toward a stimulus, as well as positive affect. Work with anger, a negative emotion often high in approach, helped clarify the role of relative left frontal cortical activity. Less work, however, examined positive emotional states varying in approach motivation and relative left frontal cortical activity. In the present research, it was predicted that positive facial expressions varying in degrees of approach motivation would influence relative left frontal cortical activity measured with electroencephalography (EEG) alpha power and task persistence measured with time working on insolvable geometric puzzles. Furthermore, relative left frontal cortical activity should positively relate to task persistence. In support of these predictions, determination compared to satisfaction facial expressions caused greater relative left frontal activity measured with EEG alpha power, a neural correlate of approach motivation. This effect remained when accounting for the contribution of muscle activity in the EEG signal, subjective task difficulty, and the extent to which participants made facial expressions. Determination compared to neutral facial expressions also caused greater self-reported interest following the puzzle task. Facial expressions did not directly influence task persistence. However, relative left frontal cortical activity was positively correlated with total time working on insolvable puzzles in the determination condition only. These results extend embodiment theories and motivational models of asymmetric frontal cortical activity.