While heart transplant recipients have significantly improved tolerance for exercise post-transplant, their aerobic exercise capabilities remain 40 – 60 per cent below normal. Blood vessel dysfunction, skeletal muscle wasting, and surgical severing of the nerves to the heart have all been implicated as factors contributing to reduced aerobic capabilities in individuals following heart transplantation. Heart transplant recipients also have dramatic pressure increases in the blood vessels within their lungs during exercise. These abnormally high pressures may result in heart dysfunction and breathlessness, causing impaired exercise tolerance. The drug Sildenafil has been shown to reduce pressure in the blood vessels of the lung. Previous research has shown that Sildenafil improved heart function during exercise among heart failure patients. Ben Esch is investigating whether Sildenafil is also beneficial to heart transplant recipients during exercise. He is testing aerobic exercise capacity among 20 heart transplant recipients both with and without Sildenafil â assessing their heart function (using cardiac ultrasound) and oxygen uptake. The results from this investigation may have important implications for cardiac rehabilitation in heart transplant recipients. If Sildenafil is shown to have a positive effect on cardiac function and exercise tolerance, its use could help heart transplant recipients train at higher intensities for longer duration during their exercise rehabilitation.
Program: Trainee
Neurophysiological markers of the control and deployment of attention in healthy individuals and individuals with attentional deficits
In order to successfully interact with the world around us, we need to be able to focus our attention on a particular object or location, move our attentional focus from one location to another, and suppress distracting information. A number of areas of the brain have been identified as part of a network of brain regions that work together to accomplish these complex cognitive processes, but there is still very little known about how these brain areas work together to control attention. A number of neuropsychological disorders, including attention deficit hyperactivity disorder (ADHD), dyslexia, schizophrenia, and depression are accompanied by deficits in the ability to focus attention and suppress distracting information in the environment. These deficits appear to originate from different underlying causes within the overall network of brain regions responsible for attention. Jessica Green is working to identify the brain areas responsible for our ability to pay attention, and determining how these brain areas interact in healthy individuals. She will then use this baseline knowledge to explore the neural basis of attentional deficits. Using electroencephalography (EEG), Green is capitalizing on recently-developed techniques for localizing the neural sources of the EEG. She will determine not only which brain areas are involved in shifting our attention between locations in space, but also how the activity changes over time as these brain areas interact with one another. In particular, she seeks to determine whether dyslexia arises from changes in attentional processing and, if so, which brain areas and connections between brain areas are affected. A better understanding of the neural basis of attentional deficits will potentially aid in the more efficient and appropriate diagnosis and treatment of these deficits.
Prediction of cardiovascular mortality in patients with coronary artery disease using plasma and genetic markers of oxidative stress
Coronary artery disease (CAD) is the leading cause of death worldwide. The consequences of CAD severely burden the Canadian health care system, and expensive therapeutic solutions have only limited capacity for preventing or reversing the disease. Oxidized low density lipoprotein particles (oxLDL) contribute to the progression of CAD. OxLDL are a harmful byproduct produced by oxidative stress, which occurs when the production of free radicals in the body exceeds the body’s ability to neutralize and eliminate them. The environmental factors that increase the risk of CAD, such as poor nutrition, smoking, obesity, and low physical activity, are the same factors that increase oxidative stress levels in the body. Claire Heslop is studying the influence of oxidative stress on long-term survival among people with CAD, and investigating genetic differences that contribute to this relationship. She is evaluating whether markers of oxidative stress in the blood, as well as markers of inflammation, can predict risk of death from cardiovascular disease in individuals with CAD. She will also investigate oxidative stress genes to determine how inherited differences affect oxidative stress in the blood, the risk of CAD, and the risk of cardiovascular death. As part of this project, the relationships between CAD, oxidative stress markers and various physiological, lifestyle and socioeconomic risk factors will also be examined. Heslopâs work will contribute to our understanding of the role oxidative stress plays in coronary artery disease. This study may inspire the creation of new tools for diagnosing CAD and predicting long-term risk.
The neural correlates of cognition in depression
Recent data suggest that 1.5 million Canadians, or 12 per cent of the population, will experience an episode of major depression at some point in their lives. For many, depression often becomes a chronic illness, with recurrent episodes. Cognitive neuroscience researchers are currently examining networks in the brain that are involved in depression, in the hope of developing better treatments and therapies for this devastating disease. MSFHR previously funded Fern Jaspers-Fayer for her Masterâs research on the electrical brain activity changes associated with Seasonal Affective Disorder (SAD). For her PhD work, Jaspers-Fayer is continuing her studies in this area. She has studied the timing and location of electrical brain signals from electroencephalograms (EEGs) that were recorded from people with symptoms of depression while they completed a number of cognitive tests. She found that although everyone pays more attention to negative events than positive ones, people with low mood will go on to ruminate about these events. This contemplation, which may become persistent and brooding, then affects how they behave. Using new techniques to localize these effects in the brain, Jaspers-Fayer is now disentangling both when and where in the brain the process of rumination begins and what conditions increase the likelihood and the duration of rumination. Jaspers-Fayerâs work will ultimately lend knowledge to our understanding of the underlying cognitive mechanisms involved in emotion, helping to pinpoint the timing and activation of brain areas involved in depression. Her research in rumination could potentially inform new approaches and therapies for treating depression.
Examining segmental sensory function and recovery in individuals with spinal cord injury using dermatomal somatosensory evoked potentials
More than 30,000 Canadians live with spinal cord injury (SCI). SCI often leads to devastating neurological deficits that markedly reduce quality of life and life expectancy. During the first year of SCI, individuals typically recover some sensory function. Sensory testing, an important component of early diagnosis and prognosis, is currently done with light touch and pin prick sensation tests. Though this method is valuable for quickly assessing sensory function, it has limitations: it is difficult to obtain reliable results from uncooperative or unconscious individuals, it does not provide a quantifiable measure of sensation, and does not identify minor changes in sensory function. In undamaged sensory pathways, electrical impulses are rapidly conducted along mixed nerves to the spinal cord, where they ascend in sensory pathways to the brain. Following SCI, the spinal cord is typically compressed and damaged but not completely severed, meaning an electrical signal can still be recorded from the brain. However, this signal is expected to be delayed and to undergo distinct changes in the path it follows to the brain. John Kramer is examining spinal cord conductivity during recovery, applying methods currently used in clinical neurology, but new to SCI practice. He is assessing conductivity at each level of the spine by stimulating specific areas of the skin’s surface with electrical current, and recording the activity with scalp electrodes. To describe the contribution of sensory function at each level to sensory recovery, he will conduct these tests multiple times over the first year of SCI. Kramer’s investigation will provide important information concerning sensory recovery following SCI. The results from this study will have implications for delivery of care for individuals with SCI, and will prove beneficial for determining the efficacy for future SCI interventional therapies
Impact of maternal fatty acid nutrition in early development – a basic science and clinical approach
There is a growing appreciation that the n-3 fatty acids, particularly docosahexaenoic acid (DHA), are important for brain development and influence cognitive, behavioural and visual function. The richest source of DHA is found in fatty fish, leading to considerable interest in the importance of fish consumption during pregnancy. Important new data shows that about 40 per cent of British Columbian women have DHA intakes below projected requirements for fetal development, and that DHA levels in BC womenâs breast milk are among the lowest in the world. During early human development, DHA is delivered from mother to baby by placental transfer (before birth) and via breast milk (after birth). Maternal intake of DHA affects the supply of DHA available to the developing fetus and infant. Currently, little is known about how DHA is transferred from mother to infant before birth, or what dietary DHA intake best supports human growth and development, and the secretion of DHA in human milk. Elizabeth Novak is conducting clinical projects to pinpoint how DHA is transported from mother to baby and to determine how much dietary DHA a mother must consume to achieve optimal levels of DHA in her baby both before and after birth. She is conducting a randomized controlled trial that tests supplementation with DHA during pregnancy. This will allow her to track maternal dietary DHA intake, blood levels of DHA, and newborn and infant blood levels of DHA and biomarkers. Novakâs studies on human milk will also involve collecting and analyzing human milk. She is also studying animal models to address questions regarding the importance of DHA in the developing fetal and neonatal liver. Ultimately, this research will result in dietary recommendations for n-3 fatty acids that support optimal development in babies.
Bayesian and non-bayesian aspects of probabilistic reasoning in healthy individuals and schizophrenia patients
One of the hallmarks of schizophrenia is the distortion of reality, including delusions. Delusions are fixed false beliefs that are held despite contradictory evidence. Delusional schizophrenia patients tend to overestimate the plausibility of potential beliefs that others would consider implausible. However, the mechanisms by which schizophrenia patients develop delusions and hold onto them in the face of contradictory evidence is not well understood. When individuals form beliefs, they assess the plausibility of a potential belief in the context of the evidence at hand. In doing so, they must consider two main factors: whether the potential belief can adequately account for the evidence at hand, and whether there are any other alternate potential beliefs that could account for this evidence. Once a belief has been established, most individuals tend to resist re-evaluating these beliefs when presented with contradictory evidence. This effect is stronger in delusional patients. Jennifer Whitman is working to determine the cognitive underpinnings of delusions. Her studies will compare delusional schizophrenia patients with non-delusional patients and healthy individuals, using simple guessing games to reveal the factors influencing how schizophrenic patients form their beliefs, how they remain fixated on them, and how this differs from non-delusional individuals. She will also conduct neuroimaging studies to identify the brain systems underlying these cognitive mechanisms. Whitmanâs work will be useful for informing how delusion-prone individuals can be taught the logical reasoning skills they need to re-evaluate current delusions and avoid developing delusions. Understanding these brain systems may also be relevant for assessing the effectiveness of different pharmacological treatments and predicting relapse and treatment responsiveness by mapping changes in these brain systems over time.
The role of Chlamydia pneumoniae and cytomegalovirus in preeclampsia: a link between preeclampsia and later atherosclerosis
Preeclampsia 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 excretion of protein in her urine are the most visible symptoms of the disease, preeclampsia also causes systemic inflammation and organ damage. When this disorder occurs early in pregnancy, it is particularly dangerous and increases a womanâs later cardiovascular risk. Normally during pregnancy, the immune system changes and women become more susceptible to infectious agents. Two infectious agents in particular, Chlamydia pneumoniae (a bacteria) and cytomegalovirus (a virus), are thought to trigger early onset preeclampsia. These agents have already been linked to the development of cardiovascular disease later in life. However, it is still unclear what role they play in the onset and development of preeclampsia and its long term cardiovascular effects. Fang Xie is investigating the mechanisms between infection, innate immune response and the development of preeclampsia. Focusing on Chlamydia pneumoniae and cytomegalovirus, she will determine how pregnant women are affected by these two infectious agents and how immune system receptors respond to the infection, including possible gene mutations and inflammatory changes associated with these two types of agents. She will also determine whether infection results in changes to blood clotting mechanisms during pregnancy. A greater understanding of the role of infectious agents in preeclampsia will help in developing targeted treatments to prevent and cure this disease, leading to improved health care for both mother and fetus.
Neuroimaging and quality of life of children with developmental coordination disorder
Developmental coordination disorder (DCD) affects six to 15 per cent of children aged five to 11. In BC, up to 48,000 of children may meet the diagnostic criteria for DCD. Children with DCD have significant motor coordination difficulties that interfere with their academic achievement and/or activities of daily living. While it was once believed that children with DCD would outgrow their motor difficulties, research suggests that these difficulties persist into adolescence and adulthood. Individuals with DCD tend to avoid social and physical activities, are at higher risk for obesity and coronary vascular disease, and experience social and emotional difficulties. There is some suggestion that DCD is related to differences in brain development, but this has yet to be confirmed. No studies have been conducted to determine how the brains of children with DCD differ from those of typically developing children, and few studies have explored the quality of life of children with this disorder. Jill Zwicker is exploring the neurobiological explanations for children with DCD, and studying how DCD impacts their quality of life. She is examining patterns of brain activation of children with and without DCD using neuroimaging techniques to determine differences in brain anatomy and activation during a fine-motor task. Zwicker will also be interviewing school-age children with DCD to determine how the disorder affects their quality of life. Zwickerâs findings will be used to educate physicians and therapists in BC and beyond regarding DCD. In the longer term, these efforts will lead to the development of scientifically grounded rehabilitation approaches specifically targeted towards enhancing brain activity, function and quality of life for children with DCD.
Exploring the social structural dynamics of health barriers and determinants of women in Vancouver's survival sex trade: an ethnographic study
A decade ago, HIV infection among downtown eastside residents exceeded those in any other part of the âdevelopedâ world. Current neighbourhood HIV prevalence estimates range between 19 and 22 per cent, and is reported higher amongst individuals who inject drugs. Risk of HIV infection is particularly profound for women who are young, coping with violence and multiple addictions, and whose survival necessitates work in the commercial sex industry. Women and girls are politically, socially and biologically more vulnerable to HIV infection. Many women in the community, including the majority of those who are part of the sex work economy, do access various health and social services, such as clinics, point-of-care and emergency services, as well as needle exchange programs. The use of condoms is also prevalent. Despite this, the rates of HIV infection remain high, particularly among sex workers who are also less likely to be treated for HIV/AIDS. Regardless of income generating strategies, HIV infected women in the community face multiple barriers to continuity of care. Suze Berkhout was previously funded by MSFHR for her early PhD work in HIV risk behaviours and health service needs among women in Vancouverâs inner city. Employing qualitative research methods and philosophical analysis, her research critically examines the impact of common stereotypes, life histories, and institutional norms and values on womenâs health care experiences, in order to unravel the paradox surrounding the health and well-being of vulnerable women. Rather than suggest that women who appear to systematically “”choose”” poor health are irrational or irresponsible, Berkhoutâs study seeks to understand what health trade-offs women may make in the context of their lives. For example, day-to-day concerns such as housing, food or caring for others may take precedence over health concerns. Likewise, womenâs previous experiences in the health system may themselves perpetuate mistrust toward health providers, leading to delays and discontinuation of medical care. Berkhoutâs findings will enable health care providers to better reflect on and respond to the experiences of patients within the health care system. Ultimately, her work could lead to more appropriate and responsive care for socially and economically disadvantaged women.