Sensorimotor deficits after stroke are commonly associated with increased activation in a number of cortical areas in the non-affected hemisphere, including primary motor and sensory cortex. Constraining the unaffected arm in individuals with stroke stimulates recovery in the use of the stroke affected arm, perhaps by reestablishing the balance of excitability between affected and non-affected cortices controlling each arm. However, the specific physiological mechanisms that follow decreasing unaffected arm use are not completely understood. Immobilization of the unaffected limb in stroke patients, by ischemia or anesthetic numbing, results in transient increases in motor function of the hemiparetic upper limb. The benefit of peripheral numbing may work through decreased proprioceptive and tactile inputs to sensory cortex which in turn diminish the overall excitability of the contralesional motor areas; the net result is a reduction in transcallosal inhibition on the affected cortex. However, beyond these preliminary findings, the role of the unaffected sensory cortex in movement deficits after stroke remains largely uncharacterized. Dr. Sean Meehan is investigating whether reducing the efficacy of proprioceptive and tactile inputs from the non-affected hand at the level of sensory cortex using continuous theta burst (cTBS), a variant of transcranial magnetic stimulation (TMS), can result not only in transient improvements in motor performance in the hemiparetic arm but also longer lasting functional changes associated with motor learning. The results of Dr. Meehanâs research may encourage rehabilitative strategies that target both the sensory and motor causes of movement deficits. The addition of sensory specific rehabilitative techniques may allow for even greater increases in function than are currently possible in individuals in the chronic phase of stroke. This line of research offers a promising new avenue for advances in the conceptualization of stroke rehabilitation.
Research Pillar: Clinical
Perceptual and attentional abnormalities in autism – understanding impaired discrimination of the eyes
Autism is a pervasive developmental disorder involving impairments in social interaction, verbal and non-verbal communication, a lack of imaginative play, and repetitive and restricted solitary activities. A critical goal of autism research is the identification of biological, behavioural and cognitive markers that will help researchers determine the links between genes and autism and aid in the development of effective diagnostic tools, as well as improve upon existing intervention and treatment programs. Of note, abnormal perceptual processing is currently a candidate marker of autism. There is mounting evidence to suggest that people with autism show specific perceptual abnormalities, and that these abnormalities may play a causal role in deficits in social processing. For example, research suggests that individuals with autism show abnormal perception of faces, with a reduced ability to discriminate visual changes to the eye area of a face, as compared with normal perception of changes to the nose and mouth. However, it is unclear whether these abnormalities are due to a deficit in perceiving visual information from the eyes, or a lack of attention to this visual information. Elina Birmingham’s research involves the use of eye tracking and a new methodology called the moving window technique, to measure the focus of attention in children with autism while they undertake visual face exploration. Her research will provide insight into several key questions regarding perceptual and attentional abnormalities as indicators of autism in children. The results of her study will contribute to the goal of identifying markers of autism, and as such may have important implications for treatment and intervention methods.
Social Attention and Visual Exploration in Children with Autism Spectrum Disorders
Autism is a severe neurological developmental disorder characterized, in part, by social impairment. A key social impairment present early in the development of children with autism is abnormal gaze following. Children with autism often do not follow the eye-gaze of others towards objects or events in the environment, which hampers their development of language and social skills. It may be that the seemingly abnormal gaze following evident in children with autism results from abnormal basic attentional responses to gaze cues. Clinical reports suggest that when in object-rich environments, these children demonstrate a diminished ability to focus on socially meaningful stimuli. Therefore, further research focusing on the ability to orient to gaze cues within complex visual environments such as classrooms, is critical. Adrienne Rombough has developed a computer task that examines orienting responses to gaze cues within complex visual scenes. In her current research she is using this program to examine the ability of children with autism to detect changes in complex visual scenes with or without the presence of gaze cues. Her study is designed to compare the performance of school-aged children with autism to that of mental age-matched, typically developing children. Her short term objective is to address the question of whether (and to what extent), the attention orienting response to gaze cues is abnormal in autism. This is the first known study to use an alternative, indirect measure of attention (i.e. change detection), to investigate gaze cueing within complex visual scenes. Over the longer term, Ms. Rombough’s findings could potentially improve the present understanding of how children with autism use social cues to explore their visual environments and how this skill set is potentially related to social impairment. The project is part of a larger research program designed to characterize the cognitive underpinnings of social impairments in autism.
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 personâs 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.
Defining Immune Abnormalities And Their Consequences In The HIV Exposed But Uninfected Child
The primary route of infection for human immunodeficiency virus (HIV), in infants is from mother to child. Following the introduction of ‘Prevention of Mother To Child Transmission’ (PMTCT), programs, HIV infection rates in newborns from mother to child (vertical transmission), have been reduced from 30 percent to less than five percent. As a result, the number of ‘HIV Exposed but Uninfected’ infants (HEU) has steadily risen. In South Africa, where 30 percent of all women of childbearing age are HIV infected, 300,000 HEU births occur per year. Recently, infection and death rates among HEU infants have been determined to be much higher than those in HIV unexposed (UE) infants. Consequently, there is an urgent need to understand why HEU infants are so vulnerable to infections. Briefly, when a person is exposed to an infecting microbe, two major arms of the immune system respond: innate immunity, which keeps the microbe at bay, and adaptive immunity, which eventually clears the infection. While it is now known that alterations in the adaptive immune system of HEU infants do take place, there is little known about how the innate immune system of HEU compared to that of the UE infant. Mr. Brian Reikie, working in collaboration with Stellenbosch University, South Africa, is conducting a pilot study to determine whether exposure to HIV, in the womb or around birth, activates the innate immune system, which then causes damage to the adaptive immune system. As well, he will explore the HIV-innate-adaptive interaction to help explain why HEU infants are so susceptible to infections. Beyond the study of HEU, this will be the first demonstration of how innate immune responsiveness correlates with development of either normal or altered adaptive vaccine immune responses over time. The findings from this project will provide the essential groundwork for urgently needed guidelines for appropriate treatment and clinical follow-up of this vulnerable population.
Do neurocognitive deficits in the evaluation of motor output contribute to falls risk in older adults?
A growing body of evidence suggests that cognitive impairment is a significant contributing factor in the increased incidence of falls among older adults. With that said, the exact neural systems within the brain that underlie an increased risk of falling remain unclear. Recently, it has been suggested that medial-frontal cortex, a region of the brain typically associated with cognitive control, plays an important role in evaluating the success or failure of movement. Therefore, one might assume that the ability of the medial-frontal system to evaluate motor output might be impaired with aging. Functional deficits within the medial-frontal system brought about by aging may result in a reduced ability to evaluate stride and/or balance, and subsequently contribute to the increased incidence of falls observed in older adults. Dr. Olave Krigolsonâs current research utilizes neuroimaging techniques to assess the effectiveness of the medial-frontal system in evaluating motor output in two groups of older adults; a group of older adults prone to falling and a group not prone to falling. Dr. Krigolson is testing the hypothesis that evaluation capabilities of the medial-frontal cortex will be diminished in older adults prone to falling compared to the control group. The findings from Dr. Krigolsonâs study will improve our understanding of the mechanisms that contribute to the increased propensity for falling evident with increasing age, and will also potentially provide a basis for the development of assessment techniques and interventions to decrease the occurrence of falls in older adults.
Imaging Early Micro-Structural Bone Changes in the Rheumatoid Hand: A High Resolution-Peripheral Computed Tomography (HR-pQCT) Study in People with Newly Diagnosed RA
Rheumatoid Arthritis (RA), affects one percent of the general population. Radiographic (x-ray), evidence of bone thinning (osteoporosis), and bony destruction (erosions), in the bone surrounding inflamed joints is an important diagnostic criterion for RA. These changes are present in the hands and feet of 80 percent of people with RA and can have profound implications with regard to the development of hand deformity, functional limitations and the need for restorative joint surgery. Early presentation of destructive bone changes is associated with a more aggressive disease progression and evidence suggests that starting disease-modifying anti-rheumatic drugs (DMARDs), soon after the diagnosis of RA may help prevent some people from developing bone damage. However, not all people with early RA respond to DMARDs, with ‘non-responders’ requiring more aggressive interventions including trials of combinations of different drug treatments or biologic response modifier drugs. Unfortunately, the time delay associated with implementing effective treatment in people with more aggressive or resistant RA means they are at greater risk for permanent bone damage. Current clinical imaging with Dual X-ray Absorptiometry (DXA), Computed Tomography (CT), and Magnetic Resonance Imaging (MRI), can detect bone damage earlier than x-ray but these tools are not able to identify the initial ‘micro-structural’ changes in the early RA hand. Dr. Lynne Feehan is characterizing early ‘micro’ structural hand bone changes over a two-year period in people with newly diagnosed RA using High Resolution – Peripheral Quantitative Computed Tomography (HR-pQCT), a promising new imaging system capable of imaging the very fine bone internal ‘micro’ detail at a resolution equivalent to the diameter of a human hair. The results of Dr. Feehanâs research could improve patientâs early access to appropriate therapy, and thereby improve their quality of life.
Predictors of Medication Adherence in Renal Transplant Patients: Self-Efficacy, Depressive Symptomology, and Neuropsychological abilities.
Chronic Kidney disease (CKD), is relatively common among middle-aged and older adults and the incidence is increasing. For example, 119 million Canadians had CKD in 1996, while by 2004 that number had reached roughly 154 million. Furthermore, just under 1,000 people received kidney transplants in Canada in 2005, while three times that many remained on wait lists that year alone. Needless to say, the successful clinical management of CKD is dependent on a number of factors. Recently, Ms. Theone Paterson and colleagues have determined that cognitive abilities are impaired in patients with CKD following successful kidney transplant, in a similar way to that seen in patients with CKD prior to kidney failure. Importantly, they also recently found that difficulties completing both traditional and everyday cognitive problems are predictive of decreased medication adherence among renal transplant patients, and that depressive symptoms partially mediate the relationship between traditional cognitive performance and medication adherence. Therefore, the extent to which real world functional issues such as adherence is predicted by traditional and everyday problem solving, depression and self-efficacy is an important issue in renal transplant, for patients, their healthcare providers, and their caregivers. In her current research program, Ms. Paterson is focusing on the relationships among traditional and everyday measures of cognitive performance, general and medication adherence-specific self-efficacy, self-reported depressive symptoms and medication adherence in people who have undergone successful renal transplantation. The results of this work will aid not only in understanding difficulties faced by transplant patients, but also in the development of interventions designed to improve adherence and consequently, real-world functioning for these patients. Additionally, the results of this research will be used to develop sensitive and valid measures to assess real-world function in patients with CKD and ultimately improve their quality of life.
The development of the corticospinal tract in premature newborns: impact of early brain injury and relationship with motor abilities
Approximately eight per cent of babies in British Columbia are born prematurely (less than 37 weeks after conception), and survival rates have improved dramatically for these infants. Motor and cognitive impairments are common among children born prematurely: five to 10 per cent will exhibit motor deficits such as cerebral palsy, and up to half will experience problems with brain functions (such as learning to speak). At school age, these delays in development can become greater concerns as they may interfere with learning and social interaction. Recent studies suggest that the developmental impairment observed may be associated with abnormal development of the brain regions responsible for motor and brain functioning. Early brain abnormalities, such as white matter injury (WMI), may underlie maturational impairments of these regions. A key brain pathway of interest is the corticospinal tract, which carries voluntary motor information from the control centre of the brain (the cortex) to muscles of the body. Elysia Adams is determining whether brain abnormalities, such as WMI, in premature newborns in their early life will affect their motor and brain function. Using advanced imaging techniques with magnetic resonance imaging (MRI), she is comparing corticospinal tract development among premature babies with and without these brain abnormalities,. This will allow her to determine whether WMI affects the development of the corticospinal tract and to establish whether later motor function can be predicted by assessing the tractâs development. Ultimately, this research could lead to ways to predict brain outcome among babies born prematurely. This would allow doctors to identify motor problems earlier and provide appropriate treatments, such as physiotherapy, to improve outcomes or prevent the long-term consequences of these developmental delays.
Video games can be good for you: an investigation of why games can be good and how to enhance their health benefits
In addition to video games being an enjoyable pastime for many people, research is increasingly indicating the beneficial effects of video game use on various cognitive abilities. Studies have demonstrated that in comparison to people who donât play video games, âgamersâ are typically better at focusing their attention and multi-tasking, and they demonstrate superior spatial processing and faster reaction times. A growing amount of anecdotal evidence suggests that video games could have health benefits, such as the use of video games as rehabilitation for stroke patients, or for improving the speed and accuracy of surgeons performing laparoscopic surgery. Although previous work has identified that video game use can lead to enhancements in attentional processing in the brain, research to date has been limited to studying how the brain orients its attention to tasks without considering the role of eye movements in this process. Joseph Chisholm is using video games to investigate the attentional differences between game players and non-game players. He is focusing on the use of âdistractorsâ â objects or events that attempt to capture an individualâs attention and distract from the task at hand. He will compare the ability of game players and non-game players to control what they pay attention to by measuring reaction times and eye movements. In identifying the mechanisms underlying how gaming enhances attentional control, this research could yield potentially novel and specialized treatment options for individuals with deficiencies in attentional processing, such as stroke patients.