Motor control deteriorates with age. For example, people over the age of 65 commit more traffic errors than younger drivers. However, it remains unclear the extent to which this increased error rate is brought about by failures of high-level cognitive control systems within the medial-frontal region of the brain as opposed to other body/brain systems. Olave Krigolson is assessing the degree to which errors by elderly individuals performing continuous motor tasks result from an impairment of error processing systems within the medial-frontal cortex. He is observing brain activity in this region of cortex during a series of experiments that will test continuous tracking and decision-making abilitiesâtwo types of tasks that are important for driving. Olaveâs research will improve our understanding of why motor errors occur more frequently among older people. Furthermore, it may help develop novel techniques for assessing the functionality of motor control systems in the elderly.
Research Pillar: Clinical
Cognitive and behavioural characterization of individuals genetically at risk for frontotemporal dementia
Frontotemporal dementia (FTD) is the second most common form of dementia affecting individuals under the age of 65. Characterized by the gradual wasting away of the brainâs frontal and anterior temporal lobes, FTD progressively affects mental function, personality and behaviour, while leaving memory largely intact. Over time, they lose the ability to organize and plan, become emotionally blunted and socially inappropriate, lose insight on the impact of their behaviour, and experience difficulty with speech and language. Currently, there is no cure for FTD and treatment methods are limited. Vulnerability to some forms of FTD has been linked to a specific gene mutation that runs in families. While the symptoms of FTD are well documented, few studies have looked at the characteristics of individuals who carry the mutation but do not yet show obvious FTD symptoms. However, research shows that even when they do not exhibit obvious symptoms of FTD, individuals who carry the gene mutation perform significantly worse on tests that measure frontal lobe functioning than family members who do not carry the mutated gene. Using measures such as cognitive testing, behavioural questionnaires and brain imaging, Amanda LaMarre is seeking to establish clinical markers of FTD in genetically at risk individuals in order to identify and distinguish the earliest symptoms. She hopes that by gaining a better understanding of the development and onset of FTD, her research will provide a base for future research aimed at preventing or slowing the progression of the disease.
Risk Assesment for Oral Cancer Prevention in the Community
Even in countries with the best survival rates, 40-50 per cent of patients with cancer of the mouth (oral cancers) do not survive five years beyond diagnosis and treatment. Late diagnosis plays a major role in this high mortality rate because oral lesions at high risk of progressing to cancer are often difficult to differentiate from lesions that are a result of trauma or infection. Denise Laronde is examining two components central to the development of an effective oral cancer screening program. She is identifying and validating tools that can be used by dental professionals to help identify which oral lesions require follow-up. She is also designing and implementing a pilot education program for dental professionals to help train them in the use of these devices. Transferring this new technology to the community may result in earlier identification of high-risk lesions, and increasing the potential for earlier treatment and ultimately, improved long-term survival.
An adaptive intensity modulated radiation therapy (IMRT) technique through complete on-line treatment plan modification
Radiation therapy uses high energy, penetrating radiation to destroy or stop development of cancer cells, a process which also causes damage to surrounding healthy tissue. Conventional radiation treatment is created using a planning software that generates a plan based on the patientâs internal geometry (position of the target cancer cells and surrounding organs), and this plan remains unchanged for the whole treatment process. The ability to more closely and uniformly target the cancer cells, which includes the ability to map and adjust to changes in the internal geometry between and during treatments, would help to minimize impact to surrounding healthy tissue. A new form of radiation therapy known as adaptive radiation therapy (ART) may hold the answer. This modality allows for modifications of the original treatment plan before each treatment fraction, while the patient is in the treatment room. However, due to time constraints, only a selected set of treatment parameters of the original plan can be modified, which limits the full potential of this technique. Ante Mestrovic is exploring the development of a method for rapid, complete treatment plan modification that characterizes the patientâs internal geometry using three-dimensional ray tracing. His goal is to develop a time-efficient way of adapting treatment plans immediately before each treatment session. This would provide for more precise targeting of cancer cells, helping to reduce radiation exposure to healthy tissue and surrounding organs and contributing to a better outcome for patients undergoing radiation therapy.
Pharmacogenetics of Mycophenolate in Thoracic Transplant Recipients: Role of UDP-Glucuronosyltransferase Genetic Polymorphisms
Thoracic (heart and/or lung) transplantation is an effective but aggressive measure for treatment of end-stage heart and lung diseases. However, rejection of the transplanted organ remains a major problem and frequently leads to organ loss and death. All transplant recipients take immunosuppressants (drugs that prevent rejection), yet over-immunosuppression exposes them to undesirable infections and other side effects. Mycophenolic acid (MPA) is an effective immunosuppressant commonly used in transplantation. However, tailoring MPA therapy is challenging due to the wide variability and unpredictability in treatment responsiveness and side effects among patients. Genetic makeup and metabolism of MPA have a significant bearing on drug responsiveness. While many studies provide better understanding of MPA in kidney transplant recipients, information on the thoracic transplant population is scarce. Lillian Tingâs research is exploring the role of genetics in determining treatment responses. The ultimate goal is to individualize regimens, even before treatment begins, for each patient in order to obtain optimal treatment response and minimal toxicity. The results from Lillianâs study will add valuable knowledge to transplantation management. It will be directly incorporated into patient care, improving patient survival and quality of life after transplantation.
Understanding social competence in Autism Spectrum Disorders: The development of a standardized measure
Autism and its related disorders are commonly described as lying along a continuum that ranges from mild to severe. As a whole, these disorders are often referred to as Autism Spectrum Disorders (ASD). ASD describes individuals who have three main areas of difficulty: communication and language; social interactions; and restricted or repetitive behaviours/interests. Although social difficulties represent the primary problem for higher functioning youth with ASD, there is a lack of standardized measures to assess the nature and severity of their social impairment. In British Columbia, it is particularly important that clinicians have access to standardized and psychometrically sound tools because ASD diagnoses are tied to publicly-funded services. Jodi Yager is developing and validating a measure of social competence that will be appropriate for use with higher functioning individuals with ASD. She anticipates this tool will ultimately be useful to mental health professionals in both clinical practice and research. Jodiâs standardized measure may play a role in assisting with important assessment and diagnostic procedures and in evaluating the effectiveness of interventions and programs (e.g. social skills training). In addition, by providing a detailed assessment of social strengths and weaknesses, this measure could prove helpful in treatment planning, such as recommending services and interventions that are specifically tailored to meet an individualâs needs. By improving our understanding and measurement of social functioning in youth with ASD, Jodiâs research will contribute to improving developmental outcomes and quality of life in this population.
Characterization of oligodendrocyte abnormalities in schizophrenia
Schizophrenia is a severe psychiatric illness affecting approximately one per cent of Canadians. While the causes are not yet fully understood, it is thought that the symptoms of this disorder may arise from abnormalities in nerve fibre connections between different brain regions. Mounting evidence suggests that a contributing factor may be abnormalities in myelin, the fatty insulating substance that surrounds nerve fibres and speeds up the transmission of nerve impulses. Studies have shown reduced density of oligodendrocytes, the brain cells that produce myelin, and altered expression of several proteins found specifically in myelinâsuggesting a possible source for impaired transmission of nerve impulses between brain regions. Through a series of investigations Dr. Clare Beasley is examining the role of oligodendrocytes in schizophrenia. She will characterize oligodendrocyte alterations in the brain in schizophrenia and examine their relationship with myelin proteins and lipids. By better understanding the connection between abnormalities in these myelin-producing cells and the symptoms of schizophrenia, she hopes to shed light on the cause of this devastating disorder.
Rostrolateral prefrontal cortex modulation using real-time fMRI feedback training in healthy volunteers and depressed patients
Depression is a common mental disorder characterized by sadness, low energy, feelings of guilt and low self-worth. Even after patients recover from a major episode of depression, they remain vulnerable to subsequent depression relapse. Such depression relapse can be triggered by a relatively mild experience of sadness, during which depression vulnerability expresses itself through reduced metacognitive awareness: the awareness of oneâs own thought processes. Neuroimaging studies suggest that increased activation within the brainâs lateral prefrontal cortexâthe same region linked to metacognitive awarenessâis a positive result of treatment for depression, and that consistent activation may reduce the risk of depressive relapse. Dr. Kalina Christoff is researching whether patients who are prone to depression can prevent relapse by learning how to better control their brain activity within this region. She is examining whether real-time feedback from functional magnetic resonance imaging (fMRI) can help patients learn to consciously modulate their brain activity and prevent or reduce relapse.
Neuromagnetic responses related to the development of orthographic perception
As normal hearing and sighted children learn to read, they gain knowledge of associations between letters or words and their related sounds. Particular brain regions and processes are implicated in readingâreflected by measurable changes in brain activityâwhich develop as children progressively gain reading ability. By recording the magnetic fields produced by the brain, Dr. Anthony Herdman is identifying the changes that occur in brain activities when children begin to recognize letters. He is also investigating what happens in childrenâs brains when they combine sight and sound in order to learn letter-sound and word-sound pairs. His goal is to gain a better understanding of the changes in cerebral activity within in the developing brain over the course reading acquisition.
Selective attention systems and their integration in children with Autism
Autism — a neurological disorder characterized by impaired communication and social interaction — is a severe and pervasive developmental disorder that usually appears in the first three years of a child’s life. Children and adults with autism have varying levels of difficulty with social interaction and communication. Early predictors of autism include the inability to notice and make meaning of social cues such as eyes and faces, while displaying an intense focus and attention to seemingly irrelevant, non-social objects such as watches or cars. These attentional disturbances are thought to play a key role in the development of perceptual abnormalitities, hindering social and emotional competence.
Dr. Grace Iarocci is investigating attentional disturbances in children with autism, Employing a series of computer tasks, she is assessing how the children’s orientation and selection attention processes are coordinated and integrated across vision and hearing. This innovative approach focuses on providing comprehensive and precise assessments of the efficiency of each of the processes of attention, as well as insight into the complexity of the organization and function of theses processes.
Dr. Iarocci is using the information gathered from this research to develop interventions that tackle the early markers underlying the behavioural symptoms of autism.