The brain perceives pain through the nociception system, which prompts increased activity in the autonomic nervous system (ANS). In turn, the ANS activates the sympathetic nervous system (SNS), creating a stress response in the body that includes increased respiration, blood pressure and heart rate. In sick patients, a strong stress response can cause serious injury. Anesthesiologists try to minimize the stress response during surgery by giving patients drugs that block nociception. Finding the appropriate balance can be challenging — too much anesthesia can make the patient very ill, while too little anesthesia increases the stress response. Anesthesiologists currently rely on a patient’s vital signs — pulse rate, blood pressure, temperature, and respiratory rate — to estimate the level of ANS activation and determine appropriate drug dosage. Unfortunately, these vital signs alone are not enough to estimate ANS activity, because they are often affected by other factors. Christopher Brouse is developing a nociception monitor that automatically determines the level of activation of a patient’s ANS. It will use computer algorithms that analyze very small, fast changes in the patient’s heart rate, called heart rate variability (HRV). Previous research has shown that HRV responds to ANS activation much more predictably than other vital signs do; therefore, HRV can provide a better estimate. With the data gathered from his first pilot pain study, Brouse is now developing and fine tuning a pain index that correlates with ANS activity. By accurately monitoring subtle vital signs, the nociception monitor has the potential to increase patient safety during and after surgery and reduce recovery times. It could also be used for patients recovering from surgery to gauge their pain and respond with the appropriate amount of drugs.
Year: 2008
Is Transcranial Magnetic Stimulation a Useful Clinical Adjunct for Predicting Stroke Occurrence and Severity following Transient Ischemic Attack? A Prospective Cohort Study
Stroke continues to be one of the leading causes of death, long-term adult disability, and illness in Canada. Approximately 1/4 of ischemic strokes are preceded by a brief episode of neurological deficit, or transient ischemic attack (TIA). During a TIA, individuals experience stroke-like symptoms that rapidly disappear. Early stroke risk in patients with TIA is considerable and North American population-based estimates of recurrent stroke range from 9.5% at 90 days, to 14.5% at 1 year. These data highlight the importance of intervention for secondary stroke prevention. However, efforts to estimate stroke risk using clinical profile and diagnostic imaging have shown variable predictive value and validity. Therefore, new markers are needed to help clearly identify high risk individuals and improve current stroke prevention strategies. Jodi Edwards is studying if cortical motor excitability, measured using a brain stimulation technique called Transcranial Magnetic Stimulation (TMS), is a marker of increased stroke risk in individuals with TIA. TMS provides information about the activity of different types of neurons in the brain and with this research, she will determine if there is an association between altered thresholds of intracortical inhibition in the cortical hemisphere affected by TIA and stroke occurrence. In addition, she is also investigating if larger asymmetries in intracortical thresholds are predictive of increased clinical severity in stroke subsequent to TIA. This research has the potential to significantly advance the understanding of the mechanisms underlying TIA and provide a new technique for the identification of high-risk patients following a TIA. Ultimately, this study has the potential to improve stroke prevention strategies and reduce recurrent stroke risk in patients with TIA.
The role of active participation in the development of perspective taking in children with and without autism
Autism and its related disorders are characterized by widespread abnormalities of social interactions and communication, as well as severely restricted interests and repetitive behaviours. These disorders are described as lying on a continuum of severity, referred to as the autism spectrum, reflecting the diversity of symptoms in children with autism. Studies indicate that one major commonality among children on the autism spectrum is an impairment in their understanding of other people’s perspective or point of view. This ability is seen as the major underlying process in children’s overall social functioning. Newly-developed theories of how children typically develop perspective taking have provided important insights for assisting children with autism to improve their social understanding. However, while intervention programs are aimed at improving children’s social competence through increasing their ability to understand someone else’s point of view, the underlying mechanisms and effects on children’s ability to reason about other people’s perspectives are not well researched. Theo Elfers is investigating how perspective-taking develops by focusing on a specific aspect of social cognition — the role of children’s active engagement in perspective-taking tasks. Studying both children with and without autism, Elfers is giving the children structured tasks that allow the child to take both perspectives in a social exchange (e.g., gift giver and gift receiver), while allotting enough time for the child to remember each perspective and prompting the child to anticipate the other’s perspective. Ultimately, this work should provide researchers and mental health professionals with insights into how perspective-taking develops, and also increase the effectiveness of future training programs aimed at fostering social competence in children on the autism spectrum.
The effects of Sildenafil on cardiac and lung function in heart transplant recipients during exercise
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 — 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.
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. Heslop’s 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 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.
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 women’s 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. Novak’s 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. Whitman’s 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.