Neurodegeneration

Department: CFMM

Award Value: Reduced Scanning Rate

This project aims to: 1: Develop a novel high resolution, distortion-free μFA dMRI approach to enable robust subfield-specific measurements of μFA in the hippocampus. 2: Investigate the sensitivity of μFA to detect subfield specific tissue changes in the hippocampus via comparisons between ipsilateral and contralateral sides of MRI negative TLE patients and between the patients and healthy controls. Aim 3: Confirm the sensitivity of μFA to hippocampal axon density via comparisons of in vivo ;FA measurements to histology of tissue resected from TLE patients who undergo surgery. These aims clearly aligns with BrainsCAN, as it aims to more "deeply understand and specifically, accurately, and robustly measure subtle cognitive markers … in human patients", as outlined in the Alignment Document.

Department: LHSC

Award Value: Reduced Scanning Rate

The purpose of this project funded by NSERC is to characterize the reproducibility of chemical exchange saturation transfer contrast (amide proton transfer (APT) and nuclear Overhouser effect (NOE)) in the brain and spine.  This contrast is sensitive to tissue intracellular pH.  We are investigating whether alterations in CEST contrast, as a proxy of tissue pH, could be used to predict recovery following spinal cord decompression surgery in people with degenerative spinal cord compression (cervical myelopathy).   CEST image acquisition in the spine is sensitive to artefacts induced by breathing, cardiac motion, and cerebral spinal fluid pulsatility.  This study will involve the recruitment of both healthy volunteers and people with spinal cord compression.  CEST data with appropriate artefact mitigation will be acquired on the 3T MRI scanner at CFMM in both the brain and spinal cord to assess inter- and intra-individual reproducibility.  Participants will be scanned twice on the same day, and also on two separate days.  In patients, data will be acquired to determine how CEST contrast changes in relation to the severity of spinal compression and the degree of motor function impairment. Motor function impairment will be measured using established measures in this patient population as well as novel metrics developed in our laboratory.  Future studies will also relate the pH changes observed in the spinal cord to motor function recover following decompression surgery.

Department: LHSC/ McGill

Award Value: Reduced Scanning Rate

Currently, the precise roles of cortical demyelination and neurodegeneration in patients with Multiple Sclerosis (MS) are under-appreciated. Our recent work suggests quantitative magnetic resonance imaging (qMRI) of cortical neuroanatomy in concert with functional neuroimaging may help identify: (i) regions of cortical sub-pial demyelination at early stages of relapsing-remitting (RR) MS, (ii) how local cortical demyelination is linked to reductions in executive function and processing speed and (iii) a greater understanding of local hyperconnectivity and global network alterations in early RRMS.

Our reserach aligns with several of the key priorities of BrainsCAN research. First, in our high field imaging study we will evaluate fundamental links between network-level changes in fMRI signals and executive function in MS. Second, we will model the impact of local structural changes associated with brain atrophy in the cortex on processing speed deficits and sensorimotor function in MS patients. Third, we will employ sensitive, high spatial resolution 7 T MRI as an innovative tool to probe microstructural changes in the cortex - changes linked to disability progression and memory impairment in MS. Lastly, our project will uniquely leverage a pre-existing collaboration between the MRI unit of the McConnell Brain Imaging Centre at McGill and the CFMM at Western University. The benefits of a reduced rate for MRI scanning for our research are multi-fold: (i) it will enable us to utilize a neuroimaging protocol that combines resting-state fMRI with high resolution T1-weighted structural neuroimaging to examine structure-function relationships in the brain of MS patients, (ii) it will enable us to increase the sample size associated with our imaging study to potentially obtain a better knowledge of MS-linked cognitive decline, (iii) it will enhance our understanding of the application of multi-modal UHF MRI for mapping laminar cortical pathology in MS, (iv) it will provide partial support for one additional HQP at the PhD level.

Department: Robarts Research

Award Value: Reduced Scanning Rate

Stroke is a severe brain cardiovascular accident and it is a leading cause of disability, including impaired speech production, motor function, and general cognition. It is estimated that two percent of Canadians live with the effects of a stroke. The recovery process includes structural and functional reorganization of damaged brain networks, but its mechanisms remain unclear. Diffusion MRI is suitable for looking at microstructure changes in the tissue, however, traditional methods lack the necessary specificity to better understand the recovery process. The goal of this project is to utilize non-human primate stroke models with advanced diffusion and microstructure imaging techniques, such as OGSE, & microFA, and inhomogeneous MT to better investigate the cognitive recovery and plasticity after stroke. We will induce parietal strokes in marmosets and correlate, longitudinally, the observed changes in the 9.4T MRI images to performance on a behavioral assessment of spatial neglect. We expect to determine the extent to which these markers of plasticity predict functional recovery. The findings will be validated with ex-vivo 9.4T MRI and histology analysis. This project aligns with the BrainsCAN goals of clinical characterization of brain disorders, aiming at a deep understand of the brain plasticity following a stroke.

Department: LHSC

Award Value: Reduced Scanning Rate

The purpose of this project is to understand how Adderall-XR treatment in multiple sclerosis (MS) patients affects brain structure over a 12 week treatment period. Reduced cognitive abilities is a common feature of multiple sclerosis patients, and can occur as early as the first demyelinating episode and prior to a confirmed diagnosis of MS. One domain of cognition that is often impacted in MS patients is processing speed. MS patients with processing speed impairment will often complain about being slower to respond, difficulty with multitasking, and taking longer to complete tasks. Amphetamines have been identified as a potential therapeutic option in this MS population with processing speed impairments. Dr. Morrow has recently completed a pre-post dose pilot study investigating the efficacy of Adderall-XR treatment for processing speed impairments. This study found a significant increase in scores on the Symbol Digit Modalities Test (SDMT) task, which is designed to assess processing speed, when compared to placebo.

Dr. Morrow is now currently conducting a Canada-wide study that is recruiting patients with processing speed impairments, where they are treated with either placebo, 10 mg, or 20 mg of Adderall-XR for a period of 12 weeks. The cognitive functioning of the patients, as well as patient reported outcomes, are assessed at baseline, week 6, and week 12. Drs. Sarah Morrow, Corey Baron, and Christian Beaulieu are interested in determining if there are any structural changes, as determined by MRI, over the treatment period that could explain the effects seen in validated tasks testing processing speed.

Department: Robarts Research

Award Value: Reduced Scanning Rate

Respiratory symptoms have been most commonly associated with coronavirus disease (COVID-19) and in severe cases may lead to death. However, there is mounting evidence to suggest the virus may also have neurologic effects. As more evidence accumulates, it is becoming clear that severely ill patients experience neurological symptoms including headache, nausea, vomiting, acute cerebrovascular disease, impaired consciousness, seizures, and loss of taste and smell. These symptoms may result from cerebral tissue damage that may have long lasting neurological consequences persisting long past the recovery phase of the initial infection. The overall goal of this proposal is to determine the incidence of brain structural and metabolic abnormalities experienced by COVID-19 patients after recovery and the association of these brain injuries with cognitive and neuropsychological dysfunction. We propose to perform a prospective observational cohort study that examines patients after they have recovered from COVID-19 illness.

All imaging will be performed at the Centre for Functional and Metabolic Mapping supported by the CFREF. This study will utilize high resolution 3D brain images of brain structure, short echo-time 1H MR spectroscopy to measure metabolite levels, and advanced diffusion tensor imaging to measure tissue microstructure. Data will be acquired on the 7T MRI in people who have recovered from the respiratory symptoms of COVID19 and may have lingering neurological effects.

Department: LHSC

Award Value: Reduced Scanning Rate

he purpose of this project is to help validate clinical use of the 7T MRI in the MS population. Currently, the standard of care is through the use of either a 1.5T or 3T MRI. Health Canada currently does not approve the use of the 7T MRI to assess clinical changes in MS progression. We will create a cross-sectional cohort of subjects already undergoing a 7T MRI. On the same day we will perform a 3T MRI, allowing us to compare lesion detection on 3T and a 7T MRI performed on the same MS subjects. We will have two experienced neuro-radiologists read both MRIs to identify and quantify MS lesions. We will compare both intra-rater and inter-rater reliability between these two neuro-radiologists.

The results of this study will provide data essential to any application for the use of the 7T MRI for clinical use. Allowing research MRIs to also be used for clinical purposes will lead to decreased costs for our public health care system, as well as improve our ability to recruit subjects for ongoing research projects.

Department: Biology

Award Value: Reduced Scanning Rate

My research examines the role of brain metabolism on age-related memory decline and Alzheimer's disease pathogenesis. There is currently great interest in cerebral aerobic glycolysis, a form of metabolism in which glucose is broken down to generate lactate even under oxygen replete conditions. A prevailing theory termed the astrocyte neuron lactate shuttle hypothesis (ANLSH) posits that astrocytes generate lactate via aerobic glycolysis, which is subsequently transported to neurons to serve as a fuel source for synaptic transmission. However, recent studies, including two from my own lab, have challenged this theory by demonstrating that lactate dehydrogenase A (LDHA), the rate limiting enzyme that catalyzes lactate production, is also highly expressed in neurons.

A previous BrainsCAN funded project enabled us to generate transgenic mice in which the Ldha gene is inducibly upregulated or inactivated within adult neurons or astrocytes. These mice will help determine the contribution of either neuronal- or astrocyte-generated lactate on learning and memory consolidation. In addition, we will examine the effect of altered neuronal/astrocytic lactate production on age-dependent memory decline. Finally, we will breed our Ldha transgenic mice lines to an Alzheimer's disease (AD) mouse model (APP/PS1) to determine the effect of elevated or repressed lactate production on cognitive decline and amyloid pathology in an AD context.

A critical aspect of this project requires confirmation that lactate levels within the cortex and hippocampus are either increased or decreased depending on the Ldha transgenic line examined. We therefore need to perform 1H-MRS imaging to measure in vivo lactate levels in both young and old control and transgenic mice. MRS data collected by the 9.4T scanner within the CFMM facility is critical to not only validate our first of a kind mouse models but to also provide unique insight into the role of lactate metabolism on learning, memory and cognitive decline associated with natural aging and AD progression.

Department: Robarts Research

Award Value: Reduced Scanning Rate

The purpose of this project is to understand how a key ion channel setting cerebral arterial tone impacts brain blood flow in animal models of dyslipidemia. Chronic dyslipidemia has been shown to be a key risk factor in the development of vascular dementia. Our prelimary work has noted that this key ion channel is strongly downregulated during the initial phases of dyslipidemia which we presume will change blood flow delivery (more specifically cerebral autoregulation). In detail, it is our plan to monitor blood flow delivery with ASL-MRI in the cortex and the striatum of mice that display mild dyslipidemia as they are exposed to a hypertensive challenge. If blood flow delivery deficits are observed, dyslipidemic mice will be exposed evaluated for cognitive deficits, work that will be done in association with CFREF scientists.

It involves the use of imaging and potentially cognitive tests to evaluate deficits in memory, attention, learning, and problem-solving. It involves collaboration of range of basic-scientists.

Department: Robarts Research

Award Value: Reduced Scanning Rate

The CESTMRICH pilot study is looking to assess whether 7T CEST MRI can identify pH differences in compartments of intracranial hemorrhage (ICH) and perihematomal edema (PHE) in acute ICH patients. Additionally, it is hypothesized that pH alterations in acute ICH are associated with the extent of PHE as an outcome determinant. Cognitive function following acute ICH will be examined using a standard Montreal Cognitive Assessment tool at 90 days to assess whether there is a relationship between the degree of perihematomal edema following acute ICH and overall cognitive function. Reduced fee rates for the CESTMRICH study would give us the opportunity to enroll more participants into this pilot study in an effort to prove our hypothesises so as to warrant further larger scaled future studies in this area.

Department: Robarts Research

Award Value: Reduced Scanning Rate

Neurosurgical treatment of drug-resistant epilepsy or brain cancer, is highly challenging and requires complete removal of the lesion while sparing important functional areas and pathways [1]. In order to achieve this, a parsimonious delineation of the target lesion must be found that incorporates information regarding pathology and function. This however can be difficult as lesion boundaries can often be diffuse [2] or not readily apparent [3]. Incorrect delineation can lead to sub-optimal surgical outcomes, for example, it is known that surgical treatment of epilepsy is almost half as effective when a lesion is not clearly delineated [3]. Risk to function is also a reality, as 8.5% of brain tumour surgeries result in major neurological deficits (e.g. loss of speech or motor control) [4]. Furthermore, as our understanding of the human brain shifts to that of complex, dynamic, and highly connected network [5], it is becoming clear that any intervention in the brain may bear a significant risk to normal cognitive functioning.

It involves the use of imaging and potentially cognitive tests to evaluate deficits in memory, attention, learning, and problem-solving. It involves collaboration of range of basic-scientists.

Department: Robarts Research

Award Value: Reduced Scanning Rate

Concussion is a common and significant public health issue and immense efforts are required to improve the diagnosis, prognosis, and treatment of this condition. Currently, there is little agreement among medical professionals on how to diagnose concussion, as its neurobiology is still poorly understood and there is a general lack of standard clinical biomarkers for concussion. A closed-head mouse model of concussion will allow for the rigorous investigation of the pathophysiological mechanisms of concussion, and the validation and implementation of biomarkers, in a tightly controlled, time- and cost-efficient manner.

The overall goal of this project is to develop imaging biomarkers for the diagnosis and prognosis of concussion and apply them to better understand its pathophysiology. Axon beading and degeneration has been demonstrated in animal models of concussion using histology. However, there is no technology that can track these types of changes in the brain in vivo, which limits our ability to perform longitudinal animal studies. In this study, a non-invasive MRI acquisition and modelling approach (implemented on the 9.4 T MRI) will be developed and applied to enable in vivo tracking of axon beading, density, and myelination (a technique termed microstructural MRI at baseline and 4 time-points post-concussion. The MRI findings will be validated by histological investigations and correlated to behavioral measures of cognition.

Department: Psychology

Award Value: Reduced Rate

Traditional tools for assessing executive functions are designed for use in traditional laboratory settings. As such, they require trained personnel for their administration and interpretation, and are burdensome to administer. Further, these tasks are often boring in that they do not engage the user, which can introduce attention and boredom related confounds into the study protocol. This may be especially true in elderly populations, as mobility issues and cognitive decline can limit the capacity of individuals to make it into a research laboratory. The mobile games included in the current study, our technology addresses this challenge by blurring distinctions between assessment and play, and laboratory and home that figure prominently in conventional methods of assessments. These games can be delivered to the target population where ever they happen to be, that are fun and engaging.

The overarching goal of this NCE Age-Well funded project is to validate the use of mobile measurements of executive functions in older adults. The study will combine novel assessments of executive functions, described above, and functional MRI. A within subject design will be used, in which participants will attend 2 imaging sessions. This will allow us to capture individual variability in functional activation and task performance. Imaging analysis will test for engagement of known executive networks using general linear models and representative similarity analyses. In addition, DTI assessments will be collected to understand how executive functions are affected by white matter tract connectivity.In the absence of reliable and continuous measurement, it is difficult for researchers and caregivers to detect sudden changes in cognitive function, evaluate the efficacy of remedial interventions, and conceptualize mechanisms of change that are intrinsic to aging.

Department: Robarts Research

Award Value: Reduced Scanning Rate

Structural and resting state functional magnetic resonance imaging will be used to investigate how high fat / high sugar (HFHS) diets alter brain architecture and relate to changes in functional networks. Brain imaging of anaesthetised mice will be conducted in the 9.4T MRI Scanner to acquire structural and resting state fMRI data. For both structural and functional MRI, a priori regions-of-interest include the striatum, prefrontal cortex and hippocampus, and the connections between these areas.

Contemporary viewpoints regard obesity as a medical condition that impacts on multiple systems, including the brain. The project will provide transformative understanding of how diet can impact the development of brain networks and high-level cognitive function. The outcomes of this project will provide the basis for significantly reducing the impact of diet-induced cognitive decline through health recommendations in the clinic and public policy regarding diets.

Department: Robarts Research

Award Value: Reduced Scanning Rate

The purpose of this study is to investigate the effects of rehabilitation on the brains of patients with degenerative cervical myelopathy (DCM). DCM is the most common cause of spinal cord dysfunction in adults, with patients describing the loss of hand dexterity as one of the most disabling symptoms limiting independence. While there are no accepted clinical protocols for post-surgical rehabilitation to recover hand function in myelopathy patients, targeted rehabilitation for other conditions affecting the brain, such as stroke, has been shown to induce cortical recruitment that can be mapped by non-invasive imaging.

Through previous collaborative efforts, co-applicants Duggal and Bartha have found that cortical reorganization and metabolic changes in the brain correlate with neurological recovery of hand function in patients recovering from spinal cord compression. Using fMRI and MR spectroscopy, we will determine if targeted task-specific rehabilitation after surgery alters brain metabolism and activation, indicative of brain plasticity, and if these imaging changes correlate with improved dexterity. Understanding how the brain responds to focused rehabilitation is the critical first step in designing patient centred neuro-restorative therapies.

Department: Psychology

Award Value: Reduced Scanning Rate

The purpose is to determine the nature of structural and functional changes that occur in the brains of humans with sensory loss. Research in normal hearing individuals has demonstrated that 7T myeloarchitecture maps correlate highly with tonotopic (core) regions of auditory cortex. One aim of the current study is to determine to what extent this relationship holds following hearing loss. This is critically important, as the ability to localize subregions of the auditory cortex of the deaf is limited by the lack of an activity-independent measure. The second aim of this resaerch is to determine to what extent auditory cortical regions are contributing to non-auditory sensory processing in the deaf, and to examine the way in which visual/somatosensory stimuli are encoded in the pattern of voxels in "auditory cortex". When one sensory modality is lost, such as in deafness, the area of cortex that would normally process stimuli in the abset modality is functionally reorganized to contribute to the remaining senses.

While this is often considered to be compensatory in nature, we hypothesize that this rededication of cortical resources may contribute to the inability of some cochlear implant users to acquire language skills similar to their normal hearing peers. The overarching goal of this program of research is to better understand how reorganized auditory cortex can be returned to auditory perception following the resumption of hearing via a cochlear prosthesis.

Department: CNS

Award Value: Reduced Scanning Rate

Many patients with neurodegenerative diseases such as Parkinson's disease (PD) experience deficits in social and emotional processes which we often take for granted. For example, PD patients have troubles expressing their own emotions, recognizing the emotions of others, and understanding irony. However, the majority of current literature fails to thoroughly establish why these symptoms occur. Therefore, the purpose of the current project is to elucidate the mechanims behind the socioemotional symptoms of Parkinson's disease. Not only will this set the groundwork for future symptomatic treatment approaches, but it will also increase our knowledge of the role of the striatum and dopamine in social and emotional behaviors, and shed light on the mechanisms behind similar socioemotional symptoms seen in other striatal/dopamine disorders (e.g., obsessive compulsive disorder, substance use disorder, schizoprhrenia).

We aim to use functional MRI to examine brain activity during several socioemotional tasks designed to measure behaviors such as emotion recognition and humor comprehension. Throughout these tasks, we will also record facial EMG data using the BrainProducts BrainAMP MR ExG amplifier and recording system, making full use of this BrainsCAN-owned equipment. Simultaneous EMG-fMRI recording is a challenge which has only been conducted by a few research groups worldwide, yet offers enormous benefits above and beyond traditional fMRI or EMG recording alone.

Department: Robarts Research

Award Value: Reduced Scanning Rate

Total hip arthroplasty (THA) is a common and successful surgical procedure to treat advanced arthritis or trauma of the hip. Seeking greater implant longevity, metal-on-metal (MoM) bearings were introduced for THA. Many of these MoM devices experienced excessive wear leading to the release of metal particles, causing adverse local tissue reactions and pain in patients. Neurological issues have also been reported in the literature. One patient described cognitive impairment and an MRI revealed signs of encephalomyelitis, which reversed when the implant was removed. Another patient with high blood levels of cobalt from a highly worn MoM THA developed rapidly progressing Parkinson disease symptoms, which also partially resolved after revision of the implant. Another case series examining 10 patients reported patients with toxic levels of cobalt and chromium due to MoM THA experienced depression and short-term memory deficit.

As THA patients are living with their implants for a longer period of time, buildup of metal ions and the body’s response to these ions are a concern, regardless of bearing material. This has never been thoroughly investigated, and it is not known what levels of metal ions might be found in the brains of THA patients. We are self-funding this pilot study to determine whether metal ion buildup is occurring in the brains of patients with 'normally' wearing THA implants. The results may lead to a much larger study proposal which would include a significant cognitive assessment component examining patients with various kinds of THA implants that have been in place from short to long term.

Department: Robarts Research

Award Value: Reduced Scanning Rate

The purpose of this project is to understand how multiple sclerosis lesions in grey and white matter affect cognitive function in a mouse model of Multiple sclerosis. Degredation of cognitive function is a common consequence of multiple sclerosis, but its origins are not well understood. This study will use novel anatomical MRI methods to delineate lesions in white matter and cortical and subcortical grey matter. We will also collect resting state fMRI and high resolution DTI at 9.4T in order to understand how tracts and connectivity are affected by the observed lesions. Additionally, validated cognitive batteries using mouse touchscreen testing will be done in the BrainsCAN Rodent Cognitive Core.

It involves the use of imaging and cognitive batteries to evaluate deficits in memory, attention, learning, problem-solving in rodents that are akin to those in patients. It involves collaboration of basic-scientists and clinicians to achieve this goal.

Department: Robarts Research

Award Value: Reduced Scanning Rate

The purpose of this project is to develop quantitative methods to assess brain function that can be used for longitudinal studies in patient cohorts. Functional MRI is very useful for studying brain function, but it is a non-quantitative technique that is difficult to interpret from session to session. Furthermore fMRI responses are highly dependent on the state of neurovascular coupling in tissue, which is altered during ageing and in disease. Quantitative methods that can measure flow and oxygenation can be used to normalize such studies across patients and sessions. This project involves the use of quantitative susceptibility mapping and cerebral blood flow mapping to obtain quantitative measures related to the Blood Oxygenation Level Dependent (BOLD) signal that underlies fMRI.

Functional MRI is the basis of much of modern day cognitive neuroscience, yet its biophysical basis is poorly understood. As a tool for mapping relative changes it is very powerful, but in order to measure absolute changes that are meaningful across patient populations and ages, other qquantitative methods are needed. These studies will be particularly important for patient chohorts with Alzheimer's or other neurodegenerative diseases where neural activity and neurovascular coupling both llikely change and need to be disentangled.

Department: Robarts Research

Award Value: Reduced Scanning Rate

The purpose of this project is to track the longitudinal evolution of various blood, proteomic, cognitive and imaging biomarkers in a cohort of female rugby players in order to determine which one are best used to make return-to-play decisions after a concussion. Our measurements to date show cumulative changes in MRI/MRS parameters even in players who are not concussed, and similar, but stronger changes in players who receive a concussion. The imaging and spectroscopy biomarkers persist even after the cognitive scores return to baseline. This poses the question as to whether the cognitive scores or the imaging measurements are the appropriate ones to use when determining the appropriate time to let the player back on the field.

It involves the use of blood, proteomic, imaging and cognitive batteries to evaluate athletes playing a concussion prone sport. Results from this study would shed light on some of the mechanisms of the concussion process and its recovery. Furthermore, the unanticipated finding that changes in the same direction as concussion in the players who do not report a concussion needs to be understood, to decide whether thr imaging and spectroscopy changes reflect a degnerative or compensatory process.

Department: BMI

Award Value: Reduced Scanning Rate

The purpose of this project is to characterize the neural mechanisms of musical memory. We will scan participants in an initial session while they listen to 16 unfamiliar music stimuli. Participants will train on half of the stimuli over the course of 2-3 weeks. We will then scan participants in a final session while they listen to all 16 music stimuli again, half familia r and half unfamiliar. ISS analysis and BOLD contrasts will be done to explore differences in familiar and unfamiliar music processing. To our knowledge, this is the first music familiarity study to control for the musical features, and actually manipulate familiarity levels. The results of this study will determine the neural correlates of music familiarity in healthy participants. Once established, these neural correlates could be explored in patients with Alzheimer's disease (AD). Memory for music is relatively spared in AD and understanding how the brain encodes musical memory in healthy participants may give us insight into why this phenomenon occurs in AD, as well as how memory for music differs from memory for other types of material.

It involves the use of imaging to evaluate memory in healthy participants to better understand memory deficitis in AD. This project will involve colaboration between labs within the Brain and Mind institute to ensure the most effective measures and protocols are used.

Department: Medical Biophysics

Award Value: Reduced Scanning Rate

Vascular and metabolic dysfunction are common in a wide variety of neurological disorders. Perfusion can be readily measured with CT or MRI. Likewise, the gold-standard for measuring glucose metabolism is FDG-PET. We are investigating an alternative contrast mechanism using an infusion of glucose and chemical exchange saturation transfer (CEST) MRI. CEST-MRI is sensitive to glucose concentration, but will be influenced by a variety of other factors, including changes in pH, blood glucose, T1 and underlying metabolites that contribute to the CEST signal. In order to untangle the glucose CEST-MRI signal, we are using a C6 rat model of glioma, which yields significant changes in vascularity and metabolism 10-12 days after surgery. We are comparing measurements made with both CT perfusion and FDG-PET to measurements made the following day with CEST-MRI during a constant infusion of glucose on the 9.4T MRI. The potential applications of MR-based measurements of glucose are multifold. Glucose could be a biodegradable, FDA-approved contrast agent that, with CEST-MRI, yields an alternative means to measure glucose metabolism and/or perfusion.

This project is focused on potentially transformative scientific research that can be translated to a variety of different brain disorders. It also has a clear path for translation into the clinical setting, where FDG and glucose are both already approved for patient use. Specifically, regional changes in glucose metabolism have been established in a wide variety of neurodegenerative disorders, including but not limited to: TBI, dementia, stroke, and epilepsy.

Department: Kinesiology

Award Value: Reduced Scanning Rate

Autonomic dysfunction (AD) may be a key contributor to the level of cognitive impairment seen in a number of neurological diseases. The most common manifestation of AD is Neurogenic Orthostatic Hypotension (NOH). NOH is defined as a drop in systolic blood pressure (SBP) ≥30mmHg within 3 minutes of standing or head-up tilt. Cognitive impairment is often reported in diseases associated with NOH. At least three mechanisms may explain the relationship between NOH and cognitive impairment. First, NOH may cause changes in cerebral blood perfusion in critical cortical regions leading to cognitive dysfunction. Evidence suggests that as patients move from sitting to standing, a drop in blood pressure elicits decreased blood flow and cerebral hypo-perfusion in various cortical regions. Furthermore, patients with long-standing chronic hypotension demonstrate reduced attention, as measured by reaction time, due to reduced blood flow in the middle cerebral artery leading to overall reduced cortical activity.

Second, changes in autonomic arousal may impact cognitive functioning through dysregulated afferent signaling to cognitive areas. Autonomic afferents enter the brain via brainstem nuclei, ascending via hypothalamic areas which contains direct and indirect connections with structures involved in cognitive functioning such as the anterior cingulate, prefrontal cortices, hippocampus and insula. These areas also make up part of the cortical autonomic network and have been correlated with changes in heart rate and blood pressure. Thus, excessive or deficient autonomic afferent signaling may impair cortical arousal of specific areas involved in autonomic and cognitive processes. Lastly, the brain and cognitive reserve hypothesis postulates that larger brain volume may protect against cognitive decline, and lifetime intellectual enrichment attenuates the effect of disease burden on cognition. As a result of cerebral hypo-perfusion, specific areas of the brain may exhibit reduced volume that could further impact cognitive functioning. Therefore, our primary objective is to: Investigate whether there is an association between NOH, brain volume and cognition. To achieve our objective, both patients and healthy controls will be compared for 1) structural and functional cortical differences 2) standard cognitive testing during an orthostatic challenge.

Department: Medical Biophysics

Award Value: Reduced Scanning Rate

Converging literature suggests that Alzheimer's disease (AD) and cerebrovascular disease not only coexist, but interact. Based on literature and our work, white matter inflammation appears to be the likeliest mechanism to explain the reciprocal interactions between AD and stroke. We have previously demonstrated experimentally that we can accelerate AD-related pathology, inflammation and memory impairment by inducing a stroke in rodent models of AD. We have developed a novel transgenic rat model of AD that overexpresses human Swedish/Indiana mutations of the amyloid precursor protein - Fisher TgF344AD. These rats do not spontaneously develop extracellular amyloid deposits (key pathological feature of AD), making it an ideal model to test the role of post-stroke white matter inflammation in initiating and/or accelerating AD related pathology. We have strong preliminary data indicating that white matter inflammation increases with age in these rats. We have histology evidence that white matter inflammation is accelerated by the induction of stroke, particularly in the transgenic AD rats.

Moreover, we have evidence that white matter inflammation correlates strongly with the level of cognitive impairment in these rats. In vivo imaging corroboration of our white matter inflammation findings is still necessary. Using the 9.4T MRI, we will acquire high resolution structural images of the brain at multiple timepoints in the TgF344AD rat mode (baseline, 7-days post-stroke, and 1-3 months post-stroke). Neuronflammation will be measured directly with a PET tracer sensitive to the translocator protein (TSPO) overexpressed in activated microglia (18F-FEPPA) using both a standalone PET system and simultaneous 3T PET/MRI at SJHC to enable accurate co-registration. Combining MRI and PET imaging modalities creates tremendous opportunities to examine both pathological and biochemical process in vivo and therefore is a powerful tool to analyze amyloid deposition along with its corresponding inflammation in TgF344AD rats following stroke.

Department: Robarts Research

Award Value: Reduced Scanning Rate

Neurosurgical treatment of drug-resistant epilepsy or brain cancer, is highly challenging and requires complete removal of the lesion while sparing important functional areas and pathways. In order to achieve this, a parsimonious delineation of the target lesion must be found that incorporates information regarding pathology and function. This however can be difficult as lesion boundaries can often be diffuse or not readily apparent. Incorrect delineation can lead to sub-optimal surgical outcomes, for example, it is known that surgical treatment of epilepsy is almost half as effective when a lesion is not clearly delineated. Risk to function is also a reality, as 8.5% of brain tumour surgeries result in major neurological deficits (e.g. loss of speech or motor control). Furthermore, as our understanding of the human brain shifts to that of complex, dynamic, and highly connected network, it is becoming clear that any intervention in the brain may bear a significant risk to normal cognitive functioning.

We are imaging epilepsy patients to improve localization of epileptogenic foci for clinical treatment, as well as improve our understanding of the how epilepsy affects brain networks. By improving in-vivo imaging in neurological disorders and targeted surgical therapies, and will involve both imaging and computational cores.

Department: Robarts Research

Award Value: Reduced Scanning Rate

The purpose of this project is to understand how acute inactivation of a cortical hub area changes large-scale functional connectivity. We will utilize unilateral chemogenetic deactivation of the frontal eye field in macaque monkeys and collect resting-state fMRI data at 7T to measure changes in whole-brain functional connectivity. We will transfect neurons in the frontal eye field with the hM4Di DREADD which leads to suppression of neural activity when activated with CNO. The fMRI experiments will be complemented by behavioural experiments outside the scanner. The study is completely novel and uses state-of-the-art chemogenetic deactivation techniques in macaque monkeys. In collaboration with Drs. McIntosh and Shen at the Rotman Research Inst., we will compare the functional connectivity results with predictions from the virtual brain model. We will exchange our data with Dr. Procyk (Lyon) and develop together pathway-specific DREADDs.

It involves the use of functional imaging and behavioural testing in nonhuman primates to understand functional connectivity changes following an acute deactivation of a frontal cortical brain area. This model will help us to understand the neural basis of changes in functional resting-state connectivity found in neurological and neuropsychiatric disorders.

Department: Kinesiology

Award Value: Reduced Scanning Rate

The purpose of this study is to evaluate procedures affecting modulation of the sympathetic nervous system, and the underlying cortical neurological substrates. Autonomic function often is closely aligned with cognitive function. Some argue that the autonomic cardiovascular response to emotion or cognitive tasks determines the perception of that task. In other cases, an autonomic response affecting heart rate, blood pressure or skin conductance, accompanies cognitive tasks possibly complicating neuroimaging outcomes. Autonomic dysfunction is suspected in cardiovascular mortality and several diseases. Previous research in our laboratory and others found that Type I/II sensory nerve stimulation (sub-motor stimulation of the forearm flexors through anesthetized skin) reduces sympathetic nerve activity and enhances parasympathetic activity in young, healthy individuals via modulating patterns of activity within the cortical autonomic network. Therefore, neuromodulation by Type I/II sensory nerve stimulation may represent a potential adjunct method to study autonomic-cogntive interactions as well as therapy for restoring autonomic balance.

It involves the use of imaging to investigate a novel form of neuromodulation that may contribute to cortical neurological studies ranging from cognitition to cardioavascular control, and neural mapping of sensory-autonomic interactions. We collaborate with many groups in these types of studies and the reduced costs of neuroimaging will allow us to broaden the range of tests in both types and ages of.

Department: Kinesiology

Award Value: Reduced Scanning Rate

Higher cortical functions, ranging from cognitive to autonomic neurological outcomes, are supported by a very high need for oxygen delivery that, in turn, exhibits complex control mechansims. Therefore, vascular impairments threaten neurological functions of all sorts and has, in fact become the emerging hypothesis regarding several neurological impairments including dementias. Heart disease is the second leading cause of death and disability globally but the mortality rates are declining in Canada (Stats Canada 2012) due to improvements in early diagnosis and treatment. However, improved survival now is increasing neurologic risk for cognitive decline and cerebrovascular risk for stroke in survivors of ischemic heart disease, leading to delayed, but arguably more burdensome, disability. Given the close association between cerebrovascular health and neurological outcomes, we need to understand the impact of peripheral vascular disease, and treatments for heart disease, on cerebrovasuclar outcomes.

The studies outlined here will use a prospective training model to evaluate a) the continuum of risk for cardiovascular disease (CVD) on brain health, emphasizing novel cerebrovascular outcomes, cortical mass, and autonomic neurologic outcomes, and b) the cerebrovascular and correlated neurologic improvements in these patients in response to six months of prescriptive exercise training. The imaging components will emphasize i) total brain structure via T1 image, ii) modified T1 to enhance subcortical conduit vessel luminal space during variations on carbon dioxide breathing (to study cerebrovasuclar reactivity, or during pharmacological perturbations (e.g., sodium nitroglycerine), iii) T2 FLAIR imaging.

Department: Robarts Research

Award Value: Reduced Scanning Rate

The purpose of this project is to understand how multiple sclerosis lesions in grey and white matter affect cognitive funciton in patients. Degredation of cognitive function is a common consequence of multiple sclerosis, but its origins are not well understood. This study will use novel anatomical MRI methods to delineate lesions in white matter and cortical and subcortical grey matter. We will also collect resting state fMRI and high resolution DTI using modified Human Connectome protocols in order to understand how tracts and connectivity are affected by the observed lesions. Additionally, validated cognitive batteries will be used by Dr. Morrow and her research staff to assess cognition at the initial, 2 year, 5 year and 7 year time points. MRI will be performed every 6 months as lesions can change over this time period.

It involves the use of imaging and cognitive batteries to evaluate deficits in memory, attention, learning, problem-solving and communication in MS patients. It involves collaboration of basic-scientists and clinicians to achieve this goal.

Department: Robarts Research

Award Value: Reduced Scanning Rate

The purpose of this project is to understand how acute inactivation of cortical or subcortical areas changes large-scale functional connectivity. We will utilize unilateral chemogenetic deactivation of cortical and subcortical areas in marmoset monkeys and collect resting-state fMRI data at 9.4T to measure changes in whole-brain functional connectivity. We will transfect neurons in selected brain areas with the hM4Di DREADD which leads to suppression of neural activity when activated with CNO. Some of the fMRI experiments will be complemented by behavioural experiments outside the scanner. The study is completely novel and uses state-of-the-art chemogenetic deactivation techniques in marmoset monkeys. In collaboration with Drs. McIntosh and Shen at the Rotman Research Inst., we will compare the functional connectivity results with predictions from the virtual brain model. We will exchange our data with Dr. Procyk (Lyon) and develop together pathway-specific DREADDs.

It involves the use of functional imaging and behavioural testing in nonhuman primates to understand functional connectivity changes following an acute deactivation of a subcortical or cortical brain area. This model will help us to understand the neural basis of changes in functional resting-state connectivity found in neurological and neuropsychiatric disorders.

Department: Robarts Research

Award Value: Reduced Scanning Rate

The purpose of this project is to understand how muscarinic and dopaminergic drugs affect large-scale functional connectivity. We will perform resting-state fMRI and task-based fMRI in awake marmoset monkeys at 9.4T. Monkeys will perform simple saccadic eye movement tasks during some of the experiments. Drugs will be administered systemically and the effects on large-scale functional connectivity will be investigated. Eye movements will be monitored during the task-based fMRI experiments using a high-field compatible MRI camera. Task-selective braina areas will be identified which can then be further explored using laminar electrophysiological recordings outside the scanner. Graph theoretical measures will be utilized to characterize drug-induced changes in functional connectivity.

It involves the use of functional imaging and behavioural testing in a novel nonhuman primate model and to explore the effects of different muscarinic and dopaminergic drugs on functional brain connectivity. This New World nonhuman primate model will help us to understand the neural basis of changes in functional resting-state connectivity found in neurological and neuropsychiatric disorders.

Department: Robarts Research

Award Value: Reduced Rate

The purpose of this project is to understand how the brain reorganizes after a frontal ischemic stroke and how changes in functional connectivity over time correlate with functional recovery of the stroke-induced spatial orientation bias. The study is novel and uses an experimentally induced stroke in macaque monkeys. We collect resting-state fMRI and high resolution DTI at 7T to correlate funcitonal connectivity at different times following the stroke with behavioural performance in saccade selection task. In collaboration with Drs. McIntosh and Shen with the Rotman Research Inst., we will compare the funcitonal connectivity resutls with predictions from the virtual brain model.

It involves the use of functional imaging and behavioural testing in nonhuman primates to evaluate functional and structural connectivity changes in a preclinical nonhuman primate mode for post-stroke recovery of a spatial extinction syndrome that has debilitating effects on the quality of life for many stroke survivors.

Department: Robarts Research

Award Value: Reduced Rate

The purpose of this project is to understand how hippocampal function and metabolism affect cognitive funciton and memory impairment in people with Alzheimer's disease. Progressive cogntive and memory decline are hallmark features of Alzheimer's disease, but the earliest metabolic and functional correlates are not well understood. This study will use novel measurements of metabolite levels in the hippocampus in combination with state of the art measurements of functional and structural connectivity between the hippocampus and other nodes of the default mode network. Data will be acquired in normal healthy elderly, people with mild cognitive impairment and people with Alzheimer's disease. In addition to a 7T MRI scan, each subject is assessed using the National Alzheimer's Coordinating Centre Neuropsychlogical Battery and a variety of memory tests including the Number Span test and the Trailmaking test. This cross sectional study will examine the relationship between the neurometabolic profile of the hippocampus and cognitive performance as well as the relationship between glutamate levels in the hippocampus and functional connectivity within the default mode network.

It involves the use of imaging and cognitive batteries to evaluate deficits in memory, attention, learning, problem-solving and communication in people with Alzhiemer's disease. It involves collaboration of basic-scientists and clinicians to achieve this goal.

Department: CNS

Award Value: Reduced Rate

The aims of this study is to prospectively define the utility of interictal 7T anatomical MRI and 7T 1H-MRS in idiopathic localization-related, temporal lobe epilepsy, assessing the changes in the NAA signal and in the NA/(Cho + Cr) ratios in areas of ictal onset (seizure onset), and comparing the results with histopathological findings in patients undergoing surgical resection. Recently, it has been shown that Glutamate exhibits a concentration dependent chemical exchange saturation transfer (CEST) effect between its amine (-NH2) group protons and bulk water protons (GluCEST). Adding GluCEST to our protocol would allow us an additional novel and accurate method of measuring Glutamate. We would be able to compare Glutamate levels obtained with GluCEST to those obtained with with MRS.

It involves the use of imaging and cognitive batteries to evaluate deficits in memory, attention, learning, problem-solving and communication in epilepsy patients. It involves the collaboration of basic scientists and clinicans to achieve this goal.

Department: CNS

Award Value: Reduced Rate

Patients with medically intractable epilepsy due to central malformations of cortical development will have fMRI and MRS studies to evaluate organization of somatosensory cortex and metabolic profile of the malformations. The aim of this study is to: 1) determine whether functional reorganization of primary sensorimotor cortex occurs in patients with epileptogenic malformations of cortical development of the rolandic and peri-rolandic regions.2) To evaluate the use of functional MRI as a tool for the assessment of brain reorganization due to malformations of cortical development.3) To determine the metabolic profile of the different malformations of cortical development, in patients with intractable epilepsy.We hypothesize that patients with some malformations will demonstrate metabolic abnormalities and also reorganized localization of cortical functions

It involves the use of imaging and cognitive batteries to evaluate deficits in memory, attention, learning, problem-solving and communication in epilepsy patients. It involves the collaboration of basic scientists and clinicans to achieve this goal.

Department: Robarts Research

Award Value: Reduced Rate

Neurosurgical treatment of brain lesions, in epilepsy or brain cancer, is highly challenging and requires complete removal of the lesion while sparing important functional areas and pathways. In order to achieve this, a parsimonious delineation of the target lesion must be found that incorporates information regarding pathology and function. This however can be difficult as lesion boundaries can often be diffuse or not readily apparent. Incorrect delineation can lead to sub-optimal surgical outcomes, for example, it is known that surgical treatment of epilepsy is almost half as effective when a lesion is not clearly delineated. Risk to function is also a reality, as 8.5% of brain tumour surgeries result in major neurological deficits (e.g. loss of speech or motor control). Furthermore, as our understanding of the human brain shifts to that of complex, dynamic, and highly connected network, it is becoming clear that any intervention in the brain may bear a significant risk to normal cognitive functioning.

We are developing novel image analytics pipelines using state-of-the-art multi-modal quantitative imaging at 3T and 7T to improve early diagnosis of neurological disorders and planning for neurosurgical interventions. These include ultra-high resolution structural imaging with computational anatomical modelling, advanced diffusion imaging of microstructure, and high-resolution functional imaging for interrogating specific circuits.

Department: CNS

Award Value: Reduced Rate

The purpose of this project to characterize the metabolic, functional, pathological and signal transduction consequences of degenerative spinal cord compression; in the spinal cord and in the brain of patients, and to validate parallel findings in a new rat model of reversible spinal cord compression. Specifically, we will confirm whether our novel rat model accurately mimics the behavioural, metabolic, and imaging changes observed in the human. Our novel rat model involves the surgical implantation of a slowly expanding hydrogel pledget at spinal segment C6. The size and diameter of the implant gradually increased over time, leading to progressively increasing spinal cord compression and injury. The purpose of this study is to correlate the severity of spinal cord compression (implant size) to behavioural phenotype and imaging correlates of ischemia and metabolism in the spinal cord and brain. Behavioural measurements will include grip strength, pain (using von Frey hairs) and gait (using beam and catwalk testing). In this longitudinal study, imaging measurements of the brain and/or spinal cord including MR spectroscopy will be made at 24 hours, 2, 4, 8, 12 and 16 weeks post-implantation. This study will utilize the 9.4T small animal MRI scanner at the CFMM. Data will be acquired in animals receiving implants and also sham operated animals.

It involves the use of MRI biomarkers and relates these to functional measurements and pain. It involves collaboration of basic-scientists and clinicians to achieve this goal.

Department: CNS

Award Value: Reduced Rate

This objective of this project is to determine whether instructed mimcry alone or in combination with intranasal oxytocin may augment brain activation as measured by fMRI BOLD signal, in brain regions related to emotion processing and empathy in patients with Frontotemporal Dementia. The project aligns with the themes and goals of BrainsCAN as it is a direct test of the potential efficacy of a behavioural intervention and pharmacologic intervention on a burdensome symptom in patients with dementia.

Participants complete two fMRI scans two weeks apart in a double blind placebo controlled randomized cross-over design. At one visit they receive intranasal oxytocin or placebo prior to the scan, on the other visit they receive the alternate treatment. Healthy participants complete one scan in which they are given placebo (though they are informed that they could receive oxytocin or placebo). Participants are debriefed after the scan. To date approximately n=17 patients with FTD have completed the protocol and n=8 controls. Our sample size goal is n=22 patients and n=20 controls.

Department: Gait and Brain

Award Value: Reduced Rate, increase participants

There are no clinically meaningful predictors of progression to dementia in people with mild cognitive impairment (MCI) and subjective cognitive impairment (SCI). The purpose of this study is to evaluate whether subtle variations in gait while performing a simple cognitive task is a reliable, easy to perform, and feasible methodology to detect those older adults at higher risk of progression to dementia and also, at higher risk of further mobility decline and falls. This study will use MRI at the following time points: Baseline, 18M and 36M. Additionally, validated cognitive batteries will be used by Dr. Montero Odasso and his research staff to assess cognition every 6 months throughout the duration of the study.

It involves the use of imaging and cognitive batteries to evaluate changes in study participants with MCI and SCI. Important questions to address are whether vascular risk factors, and brain anatomical changes, such as brain atrophy, white matter hyperintensities, correlate with gait variability, and together with further cognitive and mobility decline in people with MCI.

Department: Gait and Brain

Award Value: Reduced Rate, increase participants

The purpose of this project is to evaluate the effect of aerobic and progressive resistance training exercises, isolated or combined with cognitive training and vitamin D supplementation, in older adults with Mild Cognitive Impairment (MCI).This study will use MRI at two time points: Baseline and 6M (post intervention). Additionally, validated cognitive batteries will be used by Dr. Montero Odasso and his research staff to assess cognition at baseline, 6 month, and 1 year time points.

It involves the use of imaging and cognitive batteries to evaluate changes post-intervention (Exercise, Cognitive Training, Vitamin D) in participants with MCI. As a secondary hypothesis of this trial, all active training interventions will improve brain morphology and biochemistry compared with control placebo-interventions as defined by: increased hippocampal volume (mm3) by MRI scanning; positive localized Voxel-Based Morphometry (VBM) brain changes (z-score relative change); decreased whole brain volume of White Matter Hyper-intensities (WMHs) (mm3); and lead to beneficial hippocampal and anterior and posterior cingulate MRS metabolite changes (% increase in N-acetylaspartate, and increase in phosphocreatine metabolites).

Department: CNS

Award Value: Reduced Rate

This project is a pre/post non randomized feasibility study evaluating sedentary post- menopausal women with subjective cognitive decline taking part in an exercise intervention program (jazzercise). The primary outcomes are to understand if the jazzercise program improves physical fitness, cognition, mood, and brain function measuring exercise quantity and quality. Neuroimaging will be done at baseline and at 6 months using the 3T MRI at the CFMM and will measure changes in hippocampal volume, metabolite levels posterior cingulate and motor cortex using MRS, resting state MRI, blood flow using arterial spin labeling and tissue microstructure using DTI.

It involves the use of imaging, exercise, and cognitive batteries to evaluate if jazzersice will improve parameters of brain function including cognitive function, gait and balance in people with Subjective Cognitive Impairment due to Alzhiemer's disease.

Department: Robarts Research

Award Value: Reduced Rate

The purpose of this project is to understand how intracellular pH is altered in mouse models of brain cancer. High grade brain tumours represent a major treatment challenge with median survival times ranging from 12-18 months. As the brain tumour increases in volume patients experience a range of symptoms ranging from epileptic seizures to cognitive dysfunction. Improved diagnosis, prognosis, and treatment monitoring could lead to a significant improvement in patient quality of life including cognitive function. We are investigating whether pharmacologic manipulation of intracellular pH (acidification) in brain tumours is indicative of tumour treatment response, and can be used directly as method of tumour control by inducing apoptosis. This study will use novel measurements of tumour pH made by chemical exchange saturation transfer (CEST). Data will be in healthy people and people with brain tumours on the 7T MRI. Patients will be characterized using clinical assessments. The purpose of the human study is to assess the feasibility of pharmacologic pH-weighted CEST MRI and to quantify the magnitude of pharmacologicaly induced pH response.

It involves the development and use of pH-weighted pharmacologic MRI in a preclincial model of brain cancer and in patients with brain cancer (glioma), which result in impairments of cogntive function. It involves collaboration of basic-scientists and clinicians to achieve this goal.

Department: Robarts Research

Award Value: Reduced Rate

White Matter Hyperintensities (WMH) seen in magnetic resonance imaging (MRI), are considered markers of cerebrovascular disease (CVD) that appear in normal aging as well as in conjunction with neurodegenerative processes. Although WMH are seen and reported in a large fraction of clinical MRI scans, there are few studies characterizing neuropathology of these lesions and their etiology is not understood. Here, we will solve this problem by combining high field MRI imageing of fixed post-mortem human brain tissue with extensive histological examination of the identified WMH lesions. This work represents an important area of study due to the lack of understanding regarding the overlap of WMH with other disease processes, such as Alzheimer's Disease (AD) and CVD, and the lack of consensus regarding their clinical significance. An improved understanding of the etiology underlying WMH could lead to improved interpretation of MRI imaging findings in aging populations.

By targeting processes involved in cognitive decline across multiple diagnostic categories. It represents a multidisciplinary approach involving imaging and neuropathological examination that is based upon previous imaging studies and animal models studying white matter disease. It will be the first study to our knowledge that involves studying post-mortem WMH using advanced imaging techniques, such as quantitative multi-parametric sequences with a 7 Tesla MRI. The benefit of the reduced rate scanning will enable our group to scan a large number of post-mortem samples, with a comprehensive MR imaging protocol, allowing for observation of a large number of WMH for histological study. Furthermore, it will provide the opportunity to study a wider variety of neuropathological features due the flexibility that a larger sample with varying degrees of AD pathology and CVD offers.

Department: Robarts Research

Award Value: Reduced Rate

The purpose of this project is to characterize the behavioural, neuroimaging, neuropathological, and neurochemical effect of expressing Thr175Asp-tau or wild-type human tau in rat entorhinal cortex or hippocampus. This rat model involving bilateral innoculation of the hippocampus is being developed to study frontotemporal dysfunction occuring in conjunction with amyotrophic lateral sclerosis (ALS). We are investigating whether diffusion tensor imaging, and more specifically neurite orientation and dispersion density imaging (NODDI) can be used to detect microstructural abnormalities in this rat model that are associated with cognitive decline. This study will utilize high resolution 3D NODDI images of the rat brain acquired on the 9.4T small animal MRI scanner at the CFMM. In this longitudial study, data will be acquired from several different groups of rats at intervals ranging from weekly to quarterly depending on the severity of the model. All groups of rats are tested at 1 week, 3 months, and 6 months after inoculation for motor and cognitive function using standard behavioural (motor and cognitive) paradigms. Rats will undergo novel object recognition tasks to test working and short-term memory.

It involves the use of MRI biomarkers of cognitive decline in combination with established measures of memory performance to evaluate a novel model of frontotemporal dysfunction in ALS. It involves collaboration of basic-scientists and clinicians to achieve this goal.

Department: Robarts Research

Award Value: Reduced Rate

The purpose of this project is to demonstrate using touchscreen technology that cognitive impairments in concussed mice are similar to those in concussed humans . We will evaluate concussed mice on the 5 choice serial reaction time test (5-CSRTT) that measures attentional control in mice and on the pairwise visual discrimination (PD) test with reversal that measures behavioural flexibility. A secondary goal of this application is to investigate whether imaging and blood biomarker changes noted in our human concussion studies are also present in concussed mice. These experiments will establish a platform to investigate how different genetic and pharmacological interventions affect recovery of cognitive function after concussion with the goal of clinical translation of appropriate biomarkers and development of therapeutic interventions.

This study will utilize highs resolution 3D brain images of brain structure, short echo-time 1H MR spectroscopy to measure levels of glutamine, and resting state functional MRI to measure brain network connectivity. Data will be acquired on the 9.4T MRI in a mouse model of concussion prior to concussion and then 48 hrs, 1 week, 4 weeks, and 8 weeks post concussion. It involves the use of MRI biomarkers of cognitive decline in combination with established measures of cognitive performance to evaluate the effects of concussion. It involves collaboration of imaging scientists and neuroscientists to achieve this goal.

Department: Kinesiology

Award Value: Reduced Rate

Dementia is one of the most pressing health care issues of the 21 st century. Mild cognitive impairment (MCI) is a well-recognized risk factor for dementia, and may represent the prodromal stage of Alzheimer's disease (AD). Older adults with MCI develop AD at a rate of 10-30% annually versus 1-2% in those without MCI. Nevertheless, not all individuals with MCI convert to AD. Thus, there is a strong interest to identify patient characteristics that predict conversion. Our study aims to examine whether self-efficacy (confidence in one's ability to execute necessary courses of action to satisfy situational or domain-specific depands) may be a significant determinant of future dementia risk among older adults with MCI. OBJECTIVES: To conduct a cross-sectional pilot study with community-dwelling adults aged 65-80 years with MCI to ascertain the association between self-efficacy, cognitive function, hippocampal volume, functional activation during a memory task, and resting state functional connectivity.

We are interested in examining the relationship between a clinical population (older adults with MCI), cognitive function, and brain structure and function. This project also provides the opportunity to train one HQP (MSc student) on MRI protocol, data collection, and analysis.

Department: Kinesiology

Award Value: Reduced Rate

Dementia is one of the most pressing health care issues of the 21 st century. Importantly, older adults with pre-diabetes and diabetes experience greater cognitive decline and a higher risk of dementia than their non-diabetic counterparts. One promising intervention strategy for combating cognitive decline is exercise. Indeed, exercise has been found to improve executive functions, change functional activation patterns during the performance of a cognitive task (as measured via fMRI), and maintain or increase key brain structures, such as the hippocmapus. While these findings hold for healthy older adults and certain at-risk populations (e.g., mild cognitive impairment, MCI), it is currently unknown whether patients at-risk for diabetes would receive the same benefit from exercise. Yet targeting this population may delay or prevent the onset of not only diabetes, but also cognitive decline. OBJECTIVES: To conduct a pilot feasibility study to assess whether: 1) We can recruit and implement an exercise program in older adults at-risk for diabetes, and 2) Engaging in exercise 3x/week for 6 months will lead to changes in executive function and brain function/structure.

We are interested in examining changes in brain function and structure as the result of an exercise intervention. This project also provides the opportunity to train one HQP (MSc student) on MRI protocol, data collection, and analysis.

Department: CNS

Award Value: Reduced Rate

Patients with Frontotemporal Dementia have deficits in recognition of negative facial expressions. We have previously shown that these deficits are correlated with reduced BOLD signal in limbic regions and increased BOLD signal in dorsal regions during viewing of emotional facial expressions. FTD is hereditary in approximately 40% of cases. The objective of this project is to determine whether individuals who have a family member with Frontotemporal Dementia may show altered BOLD signal during viewing of emotional facial expressions in the pre-symptomatic state. The project aligns with the themes and goals of BrainsCAN as it explores task based fMRI with a task targeted to an early cognitive deficit as a potential novel biomarker of early neural dysfunction in a neurodegenerative disease.

Participants complete 1 fMRI scan (1 hour) as well as cognitive and behavioural tasks (facial expression recognition) outside the scanner. To date approximately n=24 family members and n=17 controls have completed the protocol. Our sample size goal is n=60 family members and n=30 controls.

Department: BMI

Award Value: Reduced Rate

Previous behavioral studies show that the auditory spatial localization ability of early-blind people improved after wearing an audio bracelet for several weeks. The bracelet emits sounds when the blind individuals move their arms. The purpose of this project is to investigate the possible neural mechanisms underlying the improvement in behavioral performance that is typically observed after blind people wear the bracelet for a few weeks. We will collect functional imaging data, resting state, and DTI data before participants wear the ABBI, immediately after or six months after they wear the ABBI to reveal any neural changes assciated with behavioral improvement.

It involves the use of imaging and behavioral evaluation to understand the neuroplastic mechanisms underlying the effectiveness of an assistive device for blind individuals. Bindness is a major health problem in Canada; more than 5.5 million Canadians have a major eye disease that could cause vision loss.

Department: LHSC

Award Value: Reduced Rate

The purpose of project is to understand how manipulation of the bacteria in the gut of people with multiple sclerosis affect immune function in patients. Degredation of cognitive function is a common consequence of multiple sclerosis, its origins are not well understood, but are thought to be secondary to damage to the brain as a result of immune dysregulation. This study will use brain MRI scans to monitor response to a novel intervention called FMT [fecal microbial transplantation].

It involves the use of imaging to assess response to a treatment with the potential to impact the long term consequences of MS damage in the brain, including what patients fear the most: cognitive deficits in memory, attention, learning, problemsolving and communication. It involves collaboration of basic-scientists and clinicians to achieve this goal.

Department: Psychology

Award Value: Reduced Scanning Rate

The purpose of this program of research is to evaluate how the onset of hearing loss affects structural and functional development of sensory cortices within sensitive periods for normal development. A number of studies across species have shown that following the onset of hearing loss, auditory cortical regions are functionally reorganized to undertake processing within the remaining sensory modalities. We have conducted a number of detailed anatomical studies seeking to quantify the changes in neural connectivity that might underlie this plasticity; however, across cortical regions, the patterns of connectivity in adult animals deafened at birth show no significant differences when compared to normal hearing animals.

The current study seeks to address these complex and conflicting results (functional change in the absence of anatomical change) by determine whether dynamic changes are occurring withing developmental windows that are not captured by examining mature animals. Measures of cortical thickness, surface area and sulcal depth will be taken from high-resolution anatomical images and will be correlated to histological measures. White matter tracts will also be reconstructed from DTI measures to examine connectivity between sensory regions. These measures will be complemented by measures of functional connectivity derived from resting-state scans. Finally, measures of anatomical development will be correlated to the onset of auditory function using fMRI measures of auditory-evoked activity. These studies will provide the first comprehensive examination of the interplay between structural and functional sensitive periods in auditory development in a robust and reliable model of human sensory processing. The results of this research program will reveal how auditory cortex changes throughout development, allowing for the subsequent onset of complex processes like speech production and language acquisition.