Year: 2009

Light-based mapping of cortical reorganization after stroke in channelrhodopsin-2 mice

Stroke is the leading cause of adult disability. Although the physical damage is irreversible, many deficits seen immediately after a stroke disappear in the following weeks. This spontaneous recovery is partly due a to reorganization of the brain’s circuitry. The adult brain was long thought to be hardwired, but new evidence has demonstrated that the firing patterns of neurons and the connections between them are constantly changing, giving the brain the flexibility to learn, form new memories and adapt to injuries. This plasticity is especially evident after a stroke. Surviving brain areas are not only able to compensate for the absence of neurons lost to stroke, but can even take on functions formerly carried out by the destroyed area. However, whether rewired neurons in reorganized brain regions maintain the ability to perform their original duties has yet to be determined. Enhancement or modification of the brain’s natural repair processes represents a logical target for new stroke treatments, of which there are few. Thomas Harrison’s research will characterise brain plasticity during the period of spontaneous recovery after stroke using a variety of methods, including a new light-based mapping technique. He will track reorganization from the level of brain regions down to single neurons in transgenic mice before and after stroke. The resulting improved understanding of stroke-induced plasticity may enable the identification of the natural mechanisms of recovery that are most beneficial, and provide the opportunity to screen drugs or therapies for their ability to facilitate these biological pathways. In a larger sense, Mr. Harrison’s research will also advance our understanding of plasticity in the adult brain, which has important implications for learning, addiction and recovery from other forms of brain damage.

Optimal timing of delivery for pregnancies with pre-existing hypertension

Chronic high blood pressure in pregnant women is associated with serious maternal and fetal complications such as poor growth, early separation of the placenta, and stillbirth. Consequently, the recommendation has been made that all women with chronic high blood pressure be considered candidates for induced delivery to reduce the risk of complications that may occur with allowing pregnancies to continue to later gestational ages. However, the optimal gestational age at which the infants should be delivered is currently unknown: delivering too early may increase the risk of respiratory complications for the infant at birth, while delaying the induction of delivery increases the risk of stillbirth. Dr. Hutcheon’s research centres on the development of a methodology to help determine the optimal gestational week for delivery. Data on maternal characteristics and pregnancy outcomes obtained from the US population birth registry as well as Canadian Birth Registries will be reviewed with a focus on the occurrence of either a serious birth complication for the newborn (such as seizures or need for prolonged assisted ventilation), or stillbirth. Among women with pre-existing high blood pressure, the risks of a poor pregnancy outcome will be calculated for each week of gestation between 36 and 42 weeks of pregnancy. Statistical models will be used to determine the gestational age range for birth during which risks to the infants are lowest. These analyses will then be repeated to determine the timing of delivery that minimizes risks of serious complications for the mother. With childbearing at older maternal ages increasing in Canada, the number of pregnancies complicated by high blood pressure is expected to increase. The results of Dr. Hutcheon’s project will help provide guidance to physicians as to the best time to deliver pregnancies complicated by pre-existing high blood pressure and, as a result, help minimise the number of adverse pregnancy outcomes in the Canadian population.

An Innovative Approach to Providing Patient Care: Examining the Role of the Nurse Practitioner in Primary Care Group Medical Visits

As the Canadian population ages, primary health care has increased its focus on the prevention and management of chronic disease in the elderly. However, access to primary care providers such as family doctors has become more difficult in recent years. Consequently, nurse practitioners (NPs) are increasingly delivering primary health services for people with chronic disease through what’s called the group medical visit (GMV). GMVs are a model of care delivery in which primary care is offered in a group format, instead of single patient/provider format. GMVs are being implemented across BC as part of the practice support program aimed at improving the primary health care system in the province. Past work indicates that patients and providers of GMVs are satisfied with GMVs. However, research on their effectiveness is limited. Laura Housden is examining the role of NPs in providing GMVs in BC and whether or not the GMV format is associated with quality patient care, such as patient self management of disease and chronic disease health indicators. To that end, she is conducting in-depth interviews with NPs currently providing GMVs. Direct observation of GMVs will be undertaken to better understand the process of the visit and context of the appointments. Chart audits will also be done to determine quality of care. The results of Ms. Housden’s research will provide a greater understanding of the role of NPs in providing GMVs, as well as the effectiveness of this care model in reaching and caring for people with chronic illnesses. Ultimately, this information could help to inform public health policy in BC.

Real-time fMRI training of functional connectivity and adaptive self-awareness

Awareness of one’s thoughts and feelings represents one of the highest mental processes in humans. Its dysregulation leads to rumination, which involves repetitively focusing on negative experiences and mental events. Rumination is consistently and strongly related to depression as both a precursor and a symptom, and therefore has important treatment implications. Given the high rates of relapse and treatment dropout in depressed individuals, a need exists for ongoing and immediate feedback in cognitive therapies that could facilitate learning and treatment compliance, and thereby improve clinical outcomes in people with depression. Real-time functional magnetic resonance imaging (fMRI), can add ongoing and immediate feedback to mindfulness-based cognitive therapy to increase its effectiveness. Mindfulness, a relatively successful treatment for depression, is an adaptive moment-to-moment awareness of mental events without controlling or elaborating (i.e. ruminating), and recruits both the anterior prefrontal cortex (PFC), (associated with cognitive and emotional self-awareness and self-regulation), and the anterior insula (associated with awareness of the self in the present moment). Previous studies show that people can successfully use real-time fMRI feedback along with awareness of their thoughts and emotions to modulate activation in the anterior PFC and the anterior insula separately. Melissa Ellamil is using real-time fMRI to examine whether it can help increase a person’s modulation ability over the functional connectivity between their anterior PFC and insular cortex and thereby improve the outcome of the strategies taught in mindfulness-based cognitive therapy. Ms. Ellamil’s research complements ongoing investigations using real-time fMRI to define functions and interactions of various regions of the brain. Her results could fine-tune the real-time fMRI feedback and self-awareness strategies and thereby enhance and prolong the results of cognitive treatments for depression.

Function of clathrin-based endocytic proteins during infections by extracellular bacterial pathogens

Most E. coli bacteria live within the intestines of humans and other animals where they help with normal digestion. However, certain types of E. coli cause disease and represent serious global health concerns. For example, diseases mediated by these pathogenic E. coli often lead to gastro-intestinal infections, resulting in severe and persistent watery or bloody diarrhea. These diseases affect a significant population, especially infants, in many developing countries and the associated mortality rates can exceed 30 percent. Previous research by Ann Lin and others has shown that clathrin, a protein that involves endocytosis, plays a key role in generating E. coli-based diarrhea in humans. Expanding on this research, Ms. Lin is now focusing on the identification of clathrin-associated endocytic components necessary for the development of enteropathogenic E. coli infections, using both in vitro and in vivo approaches. Because other bacteria and viruses (such as influenza), also control clathrin-based internalization mechanisms as part of their infection, Ms. Lin’s’s research will not only provide valuable insight into the mechanism of E. coli-based disease, but will also generate new avenues for the development of novel therapeutics to eradicate other infectious diseases.

Neural Mechanisms of Reward Learning and Cognitive Control in Children with Attention Deficit Hyperactivity Disorder

Attention Deficit Hyperactivity Disorder (ADHD), is characterized by its behavioural manifestations including difficulties with attention, hyperactivity and impulsivity. It is one of the most common childhood disorders with a prevalence rate of three to seven percent of school-aged children. ADHD carries a significant impact not only on children diagnosed with this disorder, but also on their families, schools, communities and the health care system. Numerous theories of ADHD have focused on deficits in executive functions, specifically cognitive control and the inability to inhibit inappropriate behaviours. Neuropsychological and neuroimaging studies in children with ADHD support a theory of frontal-subcortical dysfunction: specifically, a dysfunction in the midbrain dopamine (DA) system that may result in an impaired midbrain DA system and reinforcement learning, or the ability to learn to modify behaviour on the basis of rewarding and punishing stimuli in the environment. Furthermore, recent developments in reinforcement learning theory indicate that the midbrain DA system carries Reward Prediction Error (RPE) signals. Carmen Lukie is investigating how a midbrain DA system for reinforcement learning may be impaired in children with ADHD. This study follows on from her earlier research which showed that children with ADHD are particularly sensitive to the saliency of rewards. Specifically, she found that RPE signals in children with ADHD are modulated by the context in which feedback is given, and differs from what is observed in typically developing children. The current study will replicate this finding, while correcting for the limitations of the earlier study. Ultimately, the results of this research could lead to the development of novel, more effective behavioural and pharmacological treatments. Further, the research may expand to include individuals with substance abuse, pathological gambling, conduct and borderline personality disorders.

Evaluation of a Proposed Revision of the HCR-20 Violence Risk Assessment Scheme.

Violence is a serious public health concern. It embodies a considerable societal burden and its individual cost, in terms of both physical and mental health, is enormous, whether it pertains to victims, perpetrators or those close to them. Currently, legal, forensic and psychiatric institutions are confronted with the difficult task of determining whether a specific individual may be at risk of harming others. Violence risk assessments are conducted in order to find a way to reduce or manage that risk, either in the community or within institutions. Because the decisions made by mental health professionals during such assessments have serious consequences, it is essential that the decision-making processes be scientifically and clinically sound. The Historical/Clinical/Risk-Management-20 (HCR-20) represents one of the most researched and established instruments used to assess risk for community and institutional violence in offenders, civil psychiatric patients, forensic psychiatric patients, as well as males and females with mental illness, personality disorder or substance abuse problems. Since the development of the HCR-20 in 1997, a large body of data on its efficacy has been collected, and the authors concluded that some revisions were necessary. Diana Strub’s research involves an evaluation of a subscale of the revised HCR-20 assessment scheme in its entirety on a new sample of 150 individuals (i.e. offenders and mentally disordered offenders), about to be released into the community. Her work has implications for violence risk reduction and management for individuals with mental illness, personality disorders, correctional involvement and/or substance abuse problems. Such violence prevention strategies are expected, in turn, to considerably reduce physical and mental health concerns for those at risk, their victims and those close to them, as well as alleviate some of the burden placed on the health care system.

The role of Apical Junction Complex in airway epithelial repair and differentiation in asthma

Asthma is a serious global health problem, affecting over 300 million people worldwide. The disease is predominantly an inflammatory disorder of the conducting airways, and can be treated or controlled using current therapies. However, un-controlled asthma leads to continual inflammation and damage, resulting in permanent scaring which is termed airway remodeling. Airway remodeling can be defined as changes in the composition, content and organization of cellular and molecular constituents of the conducting airways. One of the structural changes that occurs as a result of airway remodeling is detachment of the cells that line the surface of the airways, called the epithelium. In normal airways, the epithelium forms a barrier against the inhaled external environment which includes aero allergens, viruses and particulate matter, through the formation of apical junction complexes (AJCs). In asthma, part of the abnormal response to inhaled allergens is thought to be due to impaired barrier function caused by damage to the airway epithelium and loss of AJCs. Emerging evidence suggests that AJCs are able to influence other aspects of epithelial function such as release of inflammatory mediators and mechanisms of epithelial repair. Building on earlier work in this area, Dr. Tillie-Louise Hackett’s current research is designed to determine whether AJCs play an important role in normal airway epithelial repair and if the mechanisms involved are altered in asthmatic patients. The results of her research will provide scientists and clinicians with a better understanding of the pathological mechanisms that contribute to multiple respiratory diseases. In addition, Dr. Hackett’s findings will open avenues for the development of new therapeutics to improve the lung health of Canadians living with obstructive lung diseases, such as asthma and Chronic Obstructive Pulmonary Disorder.