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.

Health Innovation Design and Evaluation Research Team

In their ongoing efforts to improve health outcomes, decrease health care costs, and increase administrative efficiency, health care agencies are increasingly investing in information-based technologies (IT). Recently, the Canadian government highlighted the need for developing new methods for evaluating new health sector technologies in order to provide insight into the challenges associated with increased use of IT in health care settings. This award supports the development of a team that is researching the use of IT for epidemiological data collection (EDC), also known as e-epidemiology. The team’s goals include: identifying technological, organizational, governance and implementation challenges associated with the increased use of IT for EDC; addressing data quality issues arising from increased use of IT for EDC; and improving collaborations among researchers, decision makers and technology developers across disciplines who share an interest in e-epidemiology. The team hopes to improve the quality of evidence used in decision making about information technologies used for collecting epidemiological data in BC.

Trajectories towards self-harm, suicide, and other maladaptive coping behaviours

Borderline personality disorder is a serious mental health problem characterized by heightened emotional vulnerability and difficulty modulating emotional responses. Individuals with BPD have high rates of health risk behaviours, such as suicide attempts (75 per cent), self-harm (69-80 per cent), and substance abuse (60 per cent). Despite frequent intense emotional reactions to stressful events, people with BPD lack the skills to reduce their distress through adaptive coping methods. In an effort to reduce these unpleasant emotions and feel better, persons with BPD features often resort to maladaptive coping strategies that are quick and easy to execute (e.g., self-harm, substance abuse) but have negative long-term consequences. However, not everyone with BPD engages in these risky behaviours in response to every stressor, and the specific triggers for these behaviours are largely unknown. Certain types of emotional states (e.g., shame) and life stressors (e.g., being rejected) may be particularly linked with self-destructive coping behaviours. Kristy Walters is examining the specific negative emotions or particular stressful triggers that may be strongly associated with maladaptive behaviours such as self-harm, substance abuse, or suicide. This research will also examine whether or not these relationships among emotions, stressors, and maladaptive behaviours is unique among individuals with borderline personality disorder (BPD). A better understanding of which specific emotions constitute cause for concern, or which types of negative events are more likely to result in self-destructive behaviour, will considerably improve clinicians’ ability to evaluate their client’s level of risk and better identify those clients who are in urgent need of life-saving interventions.

Characterization of the mechanical properties of collagen using optical tweezers

The collagens are a family of more than 20 different proteins, all sharing the same basic structure. Collagen is the most abundant protein in mammals, comprising more than a quarter of the total protein in the human body. Its main role is in connective tissues, such as bone, cartilage, tendons and skin, where it is a vital structural element providing support and rigidity. Even small mutations can lead to weakened tissues, and genetic diseases such as brittle bone syndrome and osteoarthritis. Understanding the mechanical properties of collagen at the molecular level is important for understanding its role in these tissues, their formation, and their degeneration. In humans it has been found that the melting temperature of collagen – the temperature at which the molecule unwinds and separates – is very close to body temperature. The melting temperatures of various types of collagen have been found to be closely linked to the body temperature of the species in which they are present. This indicates that the thermal stability of collagen may be of great relevance to the structural role it plays. Benjamin Downing is investigating how temperature affects the collagen molecule’s strength and flexibility. He is using optical tweezers – a device that employs a tightly focused laser beam to manipulate micron-sized objects – to stretch the molecule and measure its stiffness and elasticity over a range of temperatures. This will reveal how closely the mechanical and thermal stabilities of the molecule are correlated. Downing’s research will help shed light on how the structure of a molecule gives it a particular strength and flexibility, knowledge that may be useful in the future design of artificial molecules that have specific properties. This information could be relevant in the development of biomaterials with applications in tissue repair.

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 Master’s 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-Fayer’s 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.

Integrating gene expression data, interaction network information and evolutionary analysis to investigate mammalian innate immunity at the systems level

The immune response is the set of defenses our bodies mount to counter harmful microbes. The innate immune response is our first line of defense, providing protection until the adaptive immune response is activated. Unfortunately, the innate immune response can also be a double-edged sword. It can spin out of control and cause an overwhelming immune response called sepsis, which is responsible for 200,000 deaths every year in the US. The innate immune response is initiated and regulated by complex signalling pathways of genes in our cells. These pathways identify which type of microbe is invading (bacteria or viruses, for example) and mounts appropriate responses. Dr. David Lynn is investigating the genes involved in the innate immune response, how they are turned on and off in particular infections, and what goes wrong in cases of sepsis. This work generates vast quantities of data, requiring computer-based approaches (bioinformatics) to understand and handle such large datasets. Lynn’s work integrates gene expression data with information about how genes and proteins are interconnected in our cells in signalling networks or pathways – providing new information about gene interconnections influence their regulation. He is also investigating the same networks and pathways in other species such as mouse and cow, determining the differences and similarities in their innate immune response. Lynn’s work will help identify potential therapeutic or drug targets that could help safely boost the immune response. It will also highlight cases where important immunological differences make animal models unsuitable for research on human immunity.

Improved characterization of orthologs to facilitate cross-species analysis of innate immune system gene responses

The innate immune system is the body’s first line of defense to protect us from disease-causing microbes in our environment. However, the innate immune system can also generate other unintended and serious effects such as prolonged – and sometimes fatal – inflammation. The study of human systems such as the innate immune system is assisted by examining similar systems in other organisms, known as model organisms. Researchers link equivalent genes in the model organism to human genes, so that knowledge can be transferred from the model organism to humans. However, identifying equivalent genes between species can be a difficult task. The Brinkman laboratory at Simon Fraser University has developed a software program called Ortholuge that can detect pairs of genes that are likely to be “orthologs” – genes in different species that are similar to each other because they originated from a common ancestor. Orthologs are of significant interest when inferring function in humans based on different species, or when linking equivalent genes between species for large scale comparative analyses. Matthew Whiteside is working to improve the accuracy and speed of Ortholuge, adding functionality to the program that will resolve some of the more complex gene relationships. He will then use the software to perform a large-scale study of the innate immune system in humans, mice and animals important in agriculture, such as cattle. Whiteside’s work will be the first large-scale cross-species comparative analysis of the innate immune system. He hopes that this study will provide fundamental new insights regarding the evolution of innate immune system. This analysis may also highlight important innate immunity genes that are conserved between the species, with potential for identifying new therapeutic targets for immune diseases.

Spatial epidemiology of trauma: understanding and preventing injury through geographic analysis

Over the course of the last two decades, the notion that health and well-being is tied to societal and environmental circumstances that may overlap and intersect with important elements of individual experiences has been widely utilized as a means of characterizing the inequitable distribution of a wide range of health outcomes, including injuries. Importantly, the population health perspective model is transforming how we understand the complex interaction between the environment and injuries, and tailoring prevention and policy responses to address the inequitable distribution of their occurrence. Yet, there are currently no frameworks in place for how we quantify the interconnectivity between social, environmental, and geographical determinants of injury and building evidence that highlights the underlying relationship between all three factors with injuries. Addressing the ecological and geographical questions regarding this complex interaction entails integrating the current injury prevention models with the tools and analysis functions of geographic information systems (GIS). GIS are widely recognized as essential tools in public health promotion and surveillance as they allow for the integration of multiple data sources and the visual and spatial analysis of health data in relation to locations, distances, or proximities. GIS can increase our understanding of current population access to emergency medical services, the extent that injuries ‘cluster’ in certain areas and among certain population groups, as well as help researchers better understand and locate the links between people and their environments that may either reduce or increase injury risk. Nathaniel is currently applying GIS in a number of research areas in order to determine where important systems elements might be augmented to improve population access to critical care, for identifying incidence patterns that might have gone under noticed had they not been examined using GIS, as well as how this technology might be used to help researchers more accurately target prevention efforts to reach communities in-need. This research will help structure ongoing injury prevention efforts in British Columbia as well as provide future researchers with a number of frameworks for using GIS to improve our understanding of the societal, environmental, and geographic factors associated with injury.

Production of high-quality proteins in plants for screening and treatment of human lysosomal storage diseases

Lysosomes are structures that digest materials within the cell. Lysosomal storage diseases are devastating diseases caused by deficiencies of specific enzymes within the lysosomes. Mucopolysaccharidosis I (MPS I) is a progressive lysosomal storage disease that affects most organ systems. In severely affected humans, this genetic disease leads to early death because of profound disturbances to the heart, brain and other organ systems. One way to correct lysosomal enzyme deficiency is through using purified enzymes for enzyme replacement therapies (ERT). However, the current methods used to commercially produce the enzymes for ERT are prohibitively costly. Because of this, sustained financial support for ERT among affected Canadians is uncertain. Dr. Allison Kermode is exploring whether using plants as hosts to produce these human enzymes will offer a more economical way to provide ERT treatments for MPS I, as well as for Gaucher disease, another lysosomal storage disease. She will test whether plant-made human enzymes are effective as ERTs. She will also establish a plant-based system for assessing potential small molecule treatments for these diseases. Finally, in collaborative work, Kermode will test plant-made lysosomal enzymes in assays for newborn screening of lysosomal storage diseases. Some of the research will be expanded to other therapeutic proteins relevant to Type I diabetes, providing a general platform for plant production of therapeutic proteins.

Redefining community resilience: community perspectives on the intersection of gender, mental health and adaptive capacity in the context of the Mountain Pine Beetle disaster

Much of British Columbia’s forests have been infested with the mountain pine beetle (MPB), an epidemic that is predicted to result in the loss of more than 80 per cent of the province’s pine forests by 2013. The MPB is also expected to result in the widespread loss of jobs, shifts in traditional resource cultures of affected communities, and an increased risk of forest fires and other natural disasters (e.g. slides, flooding). Gender is recognized as one of the most critical determinants of disaster-related vulnerability. Women and children are disproportionately affected by disasters, reporting higher rates of stress-related health problems (e.g., post-traumatic stress, anxiety, depression), an increased risk of sexual and domestic violence, greater economic marginalization, and substantial increases in their work. They are also less likely to be involved in community-based planning and decision-making processes. Dr. Robin Cox is analyzing individual and collective stressors associated with MPB in four forestry-dependent communities: Barriere/Louis Creek, Clearwater, Quesnel and Wells. She is piloting a community-based research strategy intended to engage affected residents in each community in a series of workshops and focus group interviews. The focus of these events is to identify and elaborate community-based definitions and strategies of resilience that reflect the specific cultural, social, and political contexts of participants. The proposed study will contribute to the development of knowledge around community resilience that integrates a gender perspective, and will lead to the development of policies and procedures that are relevant and responsive to different communities affected by MPB.