2010 — 2015 |
Schon, Karin |
K99Activity Code Description: To support the initial phase of a Career/Research Transition award program that provides 1-2 years of mentored support for highly motivated, advanced postdoctoral research scientists. R00Activity Code Description: To support the second phase of a Career/Research Transition award program that provides 1 -3 years of independent research support (R00) contingent on securing an independent research position. Award recipients will be expected to compete successfully for independent R01 support from the NIH during the R00 research transition award period. |
Aerobic Exercise, Neurotrophins, and Fmri of Hippocampal Function and Structure @ Boston University (Charles River Campus)
DESCRIPTION (provided by applicant): The research proposed in this Pathways grant identifies and seeks to fill a current gap in knowledge regarding the relationship between aerobic exercise and cardiovascular fitness and functional and structural brain health in humans. The proposed human neuroimaging studies build upon a large body of existing animal research, and aim to extend this work to humans. The candidate is interested in establishing an independent research career in which she can study the effects of aerobic exercise and cardiovascular fitness on cognition and brain health in humans across the lifespan. The candidate's past and current research has included functional Magnetic Resonance Imaging (fMRI) studies of interactions between working memory and long-term memory and the role of the medial temporal lobes (including the hippocampus) and prefrontal cortex in working memory. The overall goal of this proposal is to prepare the candidate for a career as an independent scientist in translational cognitive neuroscience. Mentors include Dr. Chantal E. Stern, D.Phil., an expert in the cognitive neuroimaging of memory, Dr. Robert C. Wagenaar, Ph.D., a professor of exercise physiology and neurorehabilitation who is known for his work on movement disorders, Dr. Andrew E. Budson, M.D., an expert in cognitive and behavioral neurology, who is known for his work on cognitive dysfunction and memory dysfunction in Alzheimer's Disease, and Dr. Alice Cronin-Golomb, Ph.D. a professor of clinical psychology and an expert in the neuropsychology of aging. The goals of the research plan are to 1) establish a link between aerobic exercise, cardiovascular fitness, the functional neuroanatomy of hippocampal-dependent memory, and a neurotrophin, the Brain-Derived Neurotrophic Factor (BDNF) in humans using two memory tasks and fMRI (Specific Aim #1), 2) investigate whether a 12-week aerobic exercise intervention in healthy young and older sedentary adults is associated with an improvement in memory task performance, increased serum BDNF levels, and enhanced task-related hippocampal activity using fMRI and a pretest-posttest randomized control group design (Specific Aim #2), and 3) investigate whether the same aerobic exercise intervention in healthy young and older sedentary individuals results in increased volume in the hippocampus and/or hippocampal subfields, and cortical thickness in other brain areas using structural MRI and morphometric methods. The candidate will acquire essential training in exercise physiology and neurorehabilitation, geriatric neurology, clinical neuropsychological assessment, morphometric analyses of structural MRI images, and in clinical trial design. The project will enable the candidate to establish an externally funded research program in translational cognitive neuroscience. Aerobic exercise may be an effective and low-cost intervention resulting in healthy aging by promoting not only physical health, but also brain health. Regular moderate intensity aerobic exercise may have neuroprotective effects throughout the lifespan. PUBLIC HEALTH RELEVANCE: Regular moderate intensity aerobic exercise may be an effective and low-cost intervention for healthy aging by promoting not only physical health, but also brain health, and may have neuroprotective effects throughout the lifespan. These effects of exercise on the brain have been studied extensively in animal models, but not in humans. This set of studies aims to examine the relationship between aging, exercise, and the brain in healthy young and older individuals.
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2016 — 2017 |
Schon, Karin |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
The Entorhinal Cortex and Aerobic Exercise in Aging @ Boston University Medical Campus
? DESCRIPTION (provided by applicant): The overall goal of this project is to investigate the response of the entorhinal-hippocampal memory system to aerobic exercise training in initially physically inactive, healthy seniors. Entorhinal-hippocampal communication is critical for successful navigation and context-dependent memory formation. This region shows profound pathology in Alzheimer's disease. Entorhinal and hippocampal atrophy rates accelerate with age in cognitively intact seniors, who also show impaired navigation and reduced activity in hippocampal and parahippocampal areas during allocentric navigation. Allocentric navigation is a form of flexible navigation that depends on successful encoding of relationships between landmarks in the environment. Physical exercise consistently appears as one of the most effective interventions to attenuate cognitive decline in Alzheimer's disease, and promotes healthy cognitive and brain aging, including the hippocampus. The entorhinal cortex has direct projections to the dentate gyrus, the neurogenic zone of the hippocampus, which is known to respond strongly to exercise in animal models. Environmental enrichment promotes not only hippocampal integrity, but also in- creases cortical thickness in the entorhinal cortex in rodents. Animal research has demonstrated that physical exercise is one of the critical variables for environmental enrichment induced brain changes. In humans, it is currently unknown what mechanisms underlie these changes, and if aerobic exercise has an impact on entorhinal integrity and entorhinal-hippocampal communication. It is fundamentally important to fill this knowledge gap, because the entorhinal cortex sits at the epicenter of inputs to the hippocampus, serving as a gateway for cortical-hippocampal communications. We hypothesize that the entorhinal cortex and entorhinal-hippocampal communication are primary functional/anatomic targets of aerobic exercise. In two Specific Aims we seek to test the hypothesis that entorhinal functional integrity and entorhinal-hippocampal functional connectivity during memory task performance (Specific Aim #1) and during allocentric navigation in a virtual environment (Specific Aim #2) are enhanced following exercise training in initially physically inactive seniors and that this enhancement is positively related to changes in cognition. We will also investigate whether particular subsets of participants, such as those with poor performance on spatial reasoning tests or those with greater entorhinal atrophy, might be more responsive to aerobic exercise. To investigate these aims, we will use a randomized, controlled clinical trial of exercise training with baseline and follow-up assessments of behavioral performance on cognitive tasks of entorhinal and hippocampal integrity, aerobic fitness, and brain function using high-resolution functional and structural MRI techniques optimized for examining the entorhinal-hippocampal memory system. The proposed project is directly relevant to the mission of the National Institute on Aging through its focus on understanding the neurobiological underpinnings of the aging process with the goal to promote healthy cognitive and brain aging through lifestyle changes.
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2020 |
Schon, Karin |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Psychosocial Stressors and the Hippocampal Memory System in African American Seniors @ Boston University Medical Campus
PROJECT SUMMARY / ABSTRACT A larger percentage of African Americans than Americans of European ancestry have Alzheimer's disease (AD). The underlying causes of this health disparity are not well understood. African American seniors perform worse than white seniors on a range of cognitive tests. Differences in socioeconomic and health status account for large portions of this disparity, but differences remain. Although race has no biological basis, discrimination related to racial minority status is a salient chronic psychosocial stressor in African Americans that has negative health consequences, contributing to obesity, hypertension, and other conditions. This suggests that psychosocial chronic stress due to experiences of racism may contribute to the health disparities in AD and cognition. The hippocampus is a brain area critical for learning and memory that, together with the entorhinal cortex, is negatively impacted by both AD and chronic stress. Stress models have shown that the rate of adult neurogenesis in the hippocampus, which is the generation of new neurons in the adult brain, is negatively affected by chronic stress, aging, and AD. In addition, the hippocampus and entorhinal cortex have a high concentration of glucocorticoid receptors, which are binding sites for the ?stress hormone? cortisol. Another well-established modulator of adult neurogenesis is aerobic exercise. Aerobic exercise and chronic stress are both potent, but opposite modulators of adult neurogenesis. Increasing physical activity is one of the most effective interventions for slowing down cognitive decline in aging and AD. The goal of this research is to examine how psycho-social chronic stress due to experiences of racism affects the hippocampal memory system (Aim 1), and to examine an association between moderate-intensity physical activity and hippocampal function and structure (Aim 2A) comparing African American seniors with those of European ancestry. We will then investigate whether cortisol, measured in saliva, mediates, i.e. explains, the association between chronic stress and brain integrity, and whether moderate-intensity physical activity and race moderate the strength of the correlation between chronic stress and integrity of the hippocampus and of cortical regions known to be affected by AD (Aim 2B). We will address these questions with high-resolution functional and structural MRI to examine brain integrity. These neuroimaging techniques have the resolution to zoom in on the dentate gyrus subfield of the hippocampus, which is the primary area where adult neurogenesis occurs, while at the same time allowing examination of cortical AD signature regions. We will leverage the availability of an African American cohort in the Health Outreach Program for the Elderly (HOPE) registry at the Boston University Alzheimer's Disease Center. The proposed work could generate a new hypothesis: individuals experiencing chronic psychosocial stress due to racism may show accelerated cognitive decline consistent with AD. In the future this new hypothesis could then be tested by following HOPE participants longitudinally and could examine exercise training as a modulator. Reducing the AD health disparity among racial/ethnic groups in the U.S. is a critical public health goal.
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