Research Pillar: Clinical

The act of breathing is a complex physiological process involving the interaction of numerous respiratory muscles and a neural control network. These respiratory muscles are the only skeletal muscles in the body whose functioning is necessary to sustain human life, making their ability to resist fatigue very important. Despite this, research has shown that high intensity exercise can induce respiratory muscle fatigue. Given the life-sustaining role of the respiratory muscles, it is important to understand the mechanisms of fatigue, how it is best detected, and how the human body responds and adapts to fatigue. Also, research suggests that physiological and anatomical differences may make women more susceptible to respiratory muscle fatigue compared to men. However, there are no studies that have systematically examined sex-based differences in respiratory muscle fatigue, and the “normal” pulmonary response to exercise in women is not well understood. Jordan Guenette was previously funded by MSFHR for his early PhD work identifying the respiratory limitations women face as they age. Now, he is examining the mechanisms and consequences of respiratory muscle fatigue in men and women during whole body exercise. His study will determine if the smaller lungs and airways in women cause greater respiratory muscle fatigue compared to men. He will also investigate whether high levels of respiratory muscle work reduce blood flow to other parts of the body and are responsible for impairment of whole body exercise performance. Guenette’s project will address questions significant to both basic and clinical science, outlining how men and women differ with respect to the normal pulmonary physiology of exercise. His findings have the potential to influence exercise rehabilitation programs for a variety of patient populations, and exercise prescription to prevent disease in healthy individuals.

Cigarette smoking is directly responsible for the deaths of more than 45,000 Canadians each year. Although the majority of current smokers want to quit, smoking cessation can be extremely difficult. Since smokers are more likely to lapse after experiencing intense, persistent and distressing cravings, identifying factors that influence the severity of smoking-related thoughts, images and impulses is critical for understanding and preventing cessation relapse. Recent theories on the role of metacognitive processes in psychopathology hold promise for increasing our understanding of this important health issue. Metacognition refers to how people think about and react to unwanted thoughts and impulses. In her Master’s level research, Elizabeth found that among individuals attempting to quit smoking, metacognition is associated with nicotine craving severity and smoking cessation difficulty. Specifically, smokers who viewed their cravings as more important to control and more personally meaningful experienced more frequent, distressing and persistent cravings and were more likely to relapse one month later. Elizabeth is now building on this research, investigating the causal factors that contribute to personally meaningful interpretations of cravings, in relation to the effects of acute nicotine withdrawal and efforts to control thoughts about smoking. The results of Elizabeth’s research will help build understanding of the psychological factors that increase the risk for smoking relapse. They may also lead to innovative clinical strategies focused on appraisals and responses to cravings.

Delusions, a key characteristic of schizophrenia, are fixed false beliefs that are firmly held despite convincing evidence to the contrary. An underlying mechanism that can account for this debilitating symptom remains elusive. “Dual-stream information processing” is a decision-making model that divides reasoning into two separate components: a fast, intuitive stream, and a slower, logical stream, similar to our understanding of decisions made by the “”heart”” or “”gut”” versus those made by the “”head””. For most decisions, intuition and logical reasoning converge onto the same conclusion. However, in instances where intuition and reason do not agree, there may be processing differences between healthy people and people with schizophrenia. Healthy people show a bias toward the logical stream, prompting them to more carefully examine the available evidence. In schizophrenia, individuals may not detect conflict between the two streams and may not have a bias toward the logical conclusion. This could enable their erroneous intuitive interpretations of events to endure unchallenged, leading to delusions. William Speechley is testing this hypothesis by studying how people make sense of conflicts between the intuitive and logical streams of reasoning. Healthy individuals and delusional schizophrenia patients will be given reasoning tasks and their brain activity will be recorded using functional magnetic resonance imaging (fMRI). He predicts that healthy controls and delusional schizophrenia patients will differ when the two streams of reasoning conflict, and that the patient group will not adequately recruit logical reasoning areas of the brain during conflict. He also expects that fMRI will indicate greater activity in areas relating to intuitive processing among schizophrenics. This research will make a significant contribution to our understanding of the cognitive basis for the formation and maintenance of delusions in schizophrenia, potentially leading to more effective treatment strategies.

About 15 per cent of adults experience major depression at some time in their lives. This debilitating mental disorder can cause depressed moods, loss of energy, insomnia and, in severe cases, suicidal ideas and acts. Although current treatments such as antidepressant drugs and psychotherapy help a majority of patients, a significant number of people have a high rate of relapse. In recent years, several cognitive therapies have been developed to try to prevent relapse. One successful method trains patients to increase their ability to reflect on and change the direction of their own thoughts (called meta-cognitive awareness). Depression involves a reduction in certain parts of the brain. Functional Magnetic Resonance Imaging (fMRI) scans show depressed people have abnormally low activity in the front part of the prefrontal cortex, a region of the brain involved in planning cognitive behaviours and pleasure. fMRI scans also show an increased activation in this area of the brain when patients use reflective thinking. Kamyar Keramatian is investigating whether normal subjects and patients with depression can be trained to improve their own brain activation, by combining self-reflective therapy with real-time fMRI; a new tool that allows patients and researchers to see brain activation data as it is collected. If so, this approach could be an effective way to treat people who do not respond to conventional therapies.

Magnetic resonance imaging (MRI) is a powerful non-invasive imaging tool due to its ability to provide soft tissue contrast with high spatial resolution. Clinicians and researchers alike value MR images both for diagnosis and characterization of changes cause by disease. Recent advances have been made using MRI to image central nervous system white matter and investigate diseases that affect the white matter (such as Multiple Sclerosis), and damage to the spinal cord. The term “white matter” is derived from the white colour of nerve tracts. It appears white because of the layers of fat wrapped around each nerve fibre, called the “myelin sheath”. If the myelin sheath has been degraded or broken down, transmission of information along the fibre can be slowed down or lost completely. In the case of a narrowing of the spinal canal, the invertebral discs slip out of place and put pressure on the spinal cord, damaging the white matter tracts, resulting in symptoms like a feeling of numbness or tingling in the hands or feet. Somatosensory evoked potentials (SSEP) are a current clinical tool used to detect myelin degradation and nerve damage in the spinal cord. However, SSEP measurements are limited to only sensory pathway nerves, and cannot locate damage throughout the entire spinal cord. The UBC MRI Research Group has recently developed an MRI technique to measure myelin content in vivo, termed “myelin water imaging” (MWI), which can be applied throughout the brain and spinal cord. Erin MacMillan is applying the MWI technique to healthy adults and people suffering from narrowing of the cervical spinal canal. She hopes to find that MWI provides results consistent with SSEP measurements in sensory pathways, and identifies myelin degradation throughout the cervical spine. In addition, she will compare patient results from before and after surgery in the hopes of finding that the white matter has been repaired. If MWI proves to be an accurate measurement of myelin in the spinal cord, it could potentially be used to track myelin content during new spinal cord injury treatments aimed at degrading myelin in an effort to encourage nerve fibre repair.

Sleep apnea causes involuntary stops in breathing during sleep, up to 400 times a night. About 24 per cent of men and 9 per cent of women experience sleep apnea symptoms. People with this condition are at greater risk for stroke. Normally, we take in oxygen when we inhale and expel carbon dioxide when we exhale. During an apnea episode, breathing temporarily stops, so oxygen is not taken in and carbon dioxide accumulates. When this occurs, blood vessels in the brain expand due to an increase of carbon dioxide in the brain, which leads to an improvement in blood flow reducing the chance of brain damage from insufficient oxygen. However, this mechanism becomes less sensitive with a repeated lack of oxygen or exposure to higher than normal levels of carbon dioxide. Jordan Querido is investigating the combined effect of low oxygen and high carbon dioxide to determine which plays a greater role in decreasing the expansion of blood vessels and increasing the risk of stroke. Querido will also examine whether these repetitive exposures lessen the blood vessels’ ability to dilate during exercise, when extra oxygen is needed. An exercise program is often prescribed for sleep apnea patients, as most are overweight. This research will help to clarify whether patients are at greater risk of stroke during exercise, with the goal of designing safe exercise rehabilitation programs for sleep apnea patients.

Depression is a devastating disorder affecting approximately 1.4 million Canadians and 121 million people worldwide. While there have been many advances in depression treatment, a high rate of depression relapse remains. Numerous studies have shown that depression is associated with rumination, the tendency to dwell on thoughts and emotions. Since the majority of these thoughts and emotions are negative, rumination leads to a lower mood state. Rumination involves the difficulty of regulating emotional awareness as individuals become excessively aware of their negative emotions. A better understanding of the process of regulating emotional awareness in healthy individuals is therefore needed to address this problem in individuals suffering from depression. Rachelle Smith is exploring the regulation of emotional awareness in healthy individuals by making use of real-time functional magnetic resonance imaging (fMRI). This novel method, which has been successfully used in research on regulation of pain and sadness, enables participants to receive immediate feedback regarding the level of activation in a selected brain region as they engage in emotional awareness and perceptual awareness. Smith hopes her research will not only lead to an increased understanding of the regulation of emotional awareness in healthy individuals, but more importantly, provide a necessary framework for future studies in individuals suffering from depression. Ultimately, it could lead to new treatments for depression that allow individuals to gain increased control of their emotional awareness.