Many children who have been born prematurely experience long-term cognitive, visual and motor deficits. A number of interrelated factors that commonly follow preterm birth are believed to contribute to neurodevelopmental impairment, including newborn illness and exposure to medications, abnormal brain development in the months following birth, and a characteristic type of brain injury known as white matter injury. Currently, there is little research regarding how white matter injury and abnormal brain development lead to impaired motor and cognitive function. Dr. Steven Miller is researching brain development and injury in premature babies to understand how such injuries occur and why specific brain regions are affected. Using magnetic resonance imaging (MRI) techniques, Dr. Miller is measuring brain development and white matter injury in premature newborns shortly after birth and then again when the newborns reach term-equivalent age. Subsequent tests measuring gross and fine motor skills, language and cognition will be conducted at 18 and 36 months of age to evaluate neurodevelopmental outcome. The results of this study will provide a better understanding of the factors impacting brain growth and injury in newborns, and lead to improvements in preventing or treating brain injury in this population. Dr. Miller’s research group also studies brain development and white matter injury in other groups of newborns at high risk of neurodevelopmental impairments, such as those with heart birth defects.
Research Pillar: Clinical
Functional dysconnectivity of hippocampo-prefrontal neural systems in Schizophrenia
Schizophrenia is a brain disease that affects one per cent of Canadians — more than 300,000 people — causing hallucinations and disordered thought . Early intervention and prevention of relapse are key to minimizing the impact of schizophrenia on individuals and society, and an understanding of the brain changes that lead to first episode and relapse are important for achieving preventive care. Major aspects of schizophrenia include memory dysfunction and reality distortion, such as hallucinations and delusions. The brain systems that underlie these symptoms appear to involve neural systems in the hippocampo-prefrontal regions of the brain. While these neural systems exhibit a high degree of connectivity in healthy subjects, it is thought that dysconnectivity may be an underlying cause for schizophrenic symptoms. To demonstrate the role of impaired neural connectivity in schizophrenia, Dr. Todd Woodward is conducting neuroimaging studies to identify and characterize two hippocampal-prefrontal neural systems associated with schizophrenia. This functional and physiological understanding of the disease may allow for better prediction of first episode and relapse, in order to maximize early intervention.
Hormonal effects on neuroplasticity and behaviour
Contrary to popular belief, neurogenesis—the creation of new neurons—occurs in the adult brain in all species, including the human. Research demonstrates that hormones play a role in neurogenesis; however, research in this area is limited. Dr. Liisa Galea researches the means by which hormones regulate adult neurogenesis, influence mood, and contribute to learning and memory processes. Focusing specifically on estrogen and corticosterone, she is examining how hormonal changes during pregnancy affect the birth and survival of neurons, how stress alters these processes, and the links to behavioural changes such as depression. Determining the functional link between hormones and neurogenesis on learning, memory and depression may result in the development of hormonal therapeutic measures for promoting cognition, and new treatments to trigger neurogenesis in diseases characterized by lost brain tissue, such as Alzheimer’s and Parkinson’s.
Why are women at increased risk of chronic obstructive pulmonary disease and lung cancer? Is inflammation the missing link?
Chronic obstructive pulmonary disease (COPD) is a term for a group of respiratory diseases—such as chronic bronchitis or emphysema—in which there is chronic obstruction of airflow through the airways and lung damage. In Canada, despite the fact that more men smoke than women, the rates of chronic COPD and lung cancer in women are expected to exceed those in men within the next five years. Dr. Donald Sin is investigating why women seem more susceptible than men to COPD and lung cancer. His research proposes that women mount a more vigorous inflammatory reaction to cigarette smoke and environmental irritants than men, resulting in chronic lung and systemic inflammation that can lead to COPD and in some cases, lung cancer. Dr. Sin is comparing sex-related differences in the relationship between lung and systemic inflammation and the development of lung cancer. His research will not only shed light on why women are more susceptible to COPD and lung cancer compared to men, but may also be an important foundation for developing medications to reduce the risk.
Immunity and childhood disease
Immune white cells, such as cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, protect us from infectious diseases and cancer by killing infected or unwanted cells. Defects in the function or regulation of these cells can lead to immunodeficiency or autoimmunity. Two childhood diseases resulting from autoimmune malfunction include the common disease, type 1 diabetes (T1D), and X-linked lymphoproliferative (XLP) disease—a rare immunodeficiency. Dr. Rusung Tan studies the role of these cells in T1D and XLP. He is working to determine how defects in the molecular and cellular function of cytotoxic immune cells lead to disorders of childhood and will translate these findings into improved diagnostic tools, preventions and therapies for disease. His personal goal is to use the successes achieved in this work as models to drive the overall development of childhood immunity research in British Columbia.
Lung inflammation induced cardiovascular disease
There is substantial epidemiological evidence that inhalation of air pollution particles results in increased morbidity and mortality from heart conditions, such as heart attacks, cardiac arrhythmia, and heart failure. Recent research has shown that air pollution causes the development and progression of atherosclerosis, the underlying disease in vessels responsible for stroke and heart attacks. However, the biological mechanisms of air pollution-induced heart disease remain unclear. Dr. Stephan van Eeden is exploring at the cellular level the connection between the inhalation of air pollution particles and the development and progression of blood vessel disease (atherosclerosis). His hypothesis is that chronic lung inflammation caused by exposure to particulate matter air pollution and cigarette smoke cause a persistent, low-grade systemic inflammatory response that contributes to the development of atherosclerosis. He is conducting a series of studies to determine whether inhalation of air pollution particles destabilizes atherosclerotic plaques and trigger clot formation. This information will provide researchers and policy makers with a greater understanding of the adverse effects of air pollution on individuals’ health.
Early Nutrition, Language and Cognitive Development
Large amounts of omega-3 fatty acids are essential to support fetal and infant brain development. Omega-3 fatty acids accumulate in the central nervous system in the developing infant brain during and after pregnancy, although the brain appears to be particularly sensitive to dietary deficiencies of important essential fatty acids during intrauterine development. Before birth, essential fatty acids (those fatty acids which humans cannot form and which must be obtained from the diet) are transferred through the placenta, and after birth, through breast milk. The intake of omega-3 fatty acids in western diets is low with research demonstrating that many women following typical western diets likely have lower intakes than what is required by the developing infant before birth. Current guidelines for intake of Omega-3 fatty acids are directed at reducing the risk of chronic diseases like cardiovascular disease, and do not consider the needs of pregnant and lactating women, or the important role of omega-3 fatty acids in brain development and function. Dr. Orly Lipka is investigating whether an increase in omega-3 fatty acids during pregnancy reduced the risk of poor neurodevelopmental outcome in infants. Her research involves the use of sensitive tests of early language and problem solving ability to assess subtle delays in development secondary to nutritional deficiency during prenatal development. An important part of this work is also following up to assess the later effects in early childhood. The findings should lead to better understanding of the importance of omega-3 fatty acids with respect to cognitive and behavioral development.
The effect of resistance training on cognitive performance, cortical plasticity, and fall risk in women aged 65 to 75 years old: A 12-month randomized controlled trial
Falling and fall-related injuries among the elderly is a significant health issue for seniors in Canada. Older adults with cognitive impairment are at particular risk; 60 per cent fall annually, a rate that is twice that of their peers with normal cognition. Previous research has demonstrated that current falls prevention programs, such as multifactorial interventions, are ineffective in people with cognitive impairment. This suggests the need for an innovative approach to falls prevention in this group, such as targeting cognitive function itself to reduce falls. As a two-time MSFHR Trainee, Dr. Teresa Liu-Ambrose researched the effectiveness of exercise and rehabilitation programs for preventing falls in women at risk, and the specific dimensions of cognition associated with falls risk in older women. Building on this research, Dr. Liu-Ambrose is now investigating whether resistance training — a mode of exercise proven to reduce the physiological risk of falls in older adults — also benefits cognition. In her study of cognitively-intact women aged 65 to 75, Dr. Liu-Ambrose is determining whether a 12-month resistance training program improves high-level cognitive function. Using standard neuropsychological tests and brain imaging techniques, she will measure changes in cognitive performance and cortical function. She will also evaluate changes in physiological falls risk. Results from this novel study will provide valuable insight into the development of falls prevention programs that specifically focus on cognitive function in older adults.
Pre-eclampsia: Immunology, innovation and improvement
Pre-eclampsia is the most common dangerous complication of pregnancy, affecting the health of both mother and fetus. While high blood pressure in the mother and the loss of protein in her urine are the most visible symptoms of the disease, pre-eclampsia also causes inflammation and organ damage. The disease is a form of systemic inflammation, and is particularly dangerous when it occurs early in pregnancy. Dr. Peter von Dadelszen’s program of research covers a broad range of laboratory, clinical and health services research related to pre-eclampsia. He is studying the role of the immune system in the development and progression of the disease, as well as potential targets for the prevention of pre-eclampsia, and new screening techniques and predictive models. He is also researching new methods to modify pregnancy outcomes, including a novel disease-modifying therapy and development of a province-wide, structured approach to monitoring and managing pre-eclampsia. Through a greater understanding of the various facets of pre-eclampsia, Dr. von Dadelszen hopes to spur improvements in clinical care and health outcomes.
Global versus local processing in Balint's Syndrome
Balint’s syndrome is a rare disorder usually caused by brain injury to both sides of the parietal lobe following a stroke. This region of the brain is involved in cognition, information processing, spatial orientation, and sensations of pain and touch. People with Balint’s are unable to pay attention to more than one object at a time, experience spatial difficulty locating objects, and have trouble accurately reaching for objects. While there is a lack of research into these complex symptoms, preliminary research suggests these patients focus on the “local” elements of an object, instead of the “global” whole. For example, they may not see 🙂 as a smiling happy-face icon, but as a colon, dash or bracket. Kirsten Dalrymple is studying how Balint’s patients perceive objects by presenting them with stimuli such as the happy-face icon that can be perceived globally or locally. This research could result in rehabilitation strategies to improve patients’ ability to perceive everyday objects as others perceive them, which will improve their quality of life and ability to function normally.