Steven M. Weisberg, Ph.D. - US grants

? DESCRIPTION (provided by applicant): Spatial navigation is often difficult, even in ideal circumstances. But navigation can be profoundly impaired in many stroke victims, in patients with Parkinson's or Alzheimer's disease, and during the course of normal aging. Losing the ability to navigate can lead to dangerous behaviors like wandering, and to loss of autonomy. One possible way to support navigation is effective communication of easily interpretable spatial information. Schemas - simplified spatial depictions of concepts - offer a representational format in which spatial information can be communicated, preserving analog properties of images and categorical properties of words. Schemas could offer an encoding advantage to impaired navigators, because the capacity to process schemas may be differentially spared in neurodegenerative diseases or strokes. The goal of this project is to understand how the brain represents spatial directions in verbal, schematic, and pictorial formats, and to compare the efficiency with which different formats are processed. In service of this goal, three studies with specific, achievable goals are proposed in the current plan. In these studies, we will test whether schemas of spatial directions are represented bilaterally (using neuroimaging and brain-lesion patient methods), and if schemas are processed and translated more efficiently than words or images (using behavioral methods). We hypothesize that spatial directions are coded in format-dependent and format- independent manners. Findings from these studies will provide actionable outcomes, which will directly improve the communication of spatial directions for patients with brain lesions. In the long term, this project will inform interventions focusing n the creation and use of efficient representations of spatial directions, thereby improving the safety and autonomy of brain-damaged populations.

Project Abstract A cornerstone of cognitive neuroscience involves the idea that cognitive expertise can be tracked through focal changes in gray matter. One proposed mechanism for how this could work is that changes in synaptic plasticity result in dendritic growth, which in turn result in volumetric increase in gray matter observable with MRI. Consistent with this, one highly influential study suggested that taxi-drivers, who routinely employ cognitive maps and their memory of environments to navigate, have an enlarged posterior hippocampus compared to healthy control subjects and bus-drivers. A recent large- sample study from co-PI Weisberg, however, found no correlation between hippocampal volume and navigational performance in a city-like virtual reality task. Recent work has also cast doubt on whether gray matter volume changes are an appropriate measure of plasticity as they also likely involve changes in vascularization and other difficult to isolate factors. Both task-related functional and resting state connectivity offer a novel and powerful means of assaying brain wide changes potentially better related to plasticity. Such measures could also arguably be better candidates for tracking changes in skill acquisition. Here, we propose to resolve the issues above, and additionally attempt to separate navigation vs. memory functions, by having one group of participants undergo intensive training in orientation and another group undergo intensive training in episodic memory (Aim 1). We will obtain pre- and post-training measures of structural brain volume, task-related functional connectivity, and resting state connectivity to determine whether and how novel cognitive skill acquisition affects these neural measures. In addition, we will collect structural brain scans and behavioral measures from published studies to attempt understand what brain regions correlate with navigation and memory performance (Aim 2). This will allow us to perform a meta- analysis of a large sample of studies to determine how regional brain volume correlates with individual variability in these two important cognitive functions. The expected outcomes of this proposal are a better understanding of how focal gray matter vs. connectivity, as measured with MRI, relate to memory vs. navigation skills. Such outcomes could influence cognitive or stimulation therapies for stroke patients by providing insight into what brain regions or networks to target to mitigate cognitive decline.

Project Summary: Spatial navigation is an essential task for living a safe, independent life. Spatial navigation skills decline in normal aging and become progressively impaired in patients with Alzheimer?s disease (AD)1,2, severely impacting their daily life function, independence, and health3. Despite the use of compensatory navigational tools like signs, maps, and verbal directions, supporting spatial navigation in older adults and those with age-associated neurodegenerative disease remains a challenge. A major impediment to designing interventions is the limited understanding of how spatial direction comprehension is affected by the normal aging process and neurodegenerative disease. The goal of this project is to determine how normal aging and age-associated neurodegenerative disease affect spatial direction comprehension, and to elucidate the neural mechanisms underpinning spatial direction comprehension in healthy young and older adults. Our primary hypothesis is that spatial direction comprehension is supported as a result of increased connectivity between regions of the brain dedicated to encoding individual formats (i.e.,visual scenes, arrows, and words), which will result in specific patterns of impairment among older adults and those with amnestic mild cognitive impairment (aMCI), a precursor to Alzheimer?s disease. We also hypothesize that the intraparietal sulcus (IPS) ? a region that encodes spatial directions with respect to the navigator's current facing direction ? will function as a hub by computing spatial directions from all representational formats, an idea which has been supported by recent advances in fMRI. To test these hypotheses, the candidate will employ converging methodologies from cognitive neuroscience, including advanced functional magnetic resonance imaging techniques (network neuroscience and functional connectivity), and behavioral assessment of healthy young adults and older adults, and patients with amnestic mild cognitive impairment (aMCI). This award will enable the candidate to learn critical new methodologies, which will help uncover the neural instantiation of spatial direction comprehension. Through research projects and training experiences, the candidate will apply these methodologies to test new hypotheses and questions about how spatial direction comprehension deteriorates in older adults and in patients with age-related dementias. This research proposal will be undertaken at the University of Florida ? an elite research institution with access to fMRI, a large population of older adults with and without age-related dementia, and experts in network neuroscience, neurology, and cognitive neuroscience. This award will also provide critical preliminary data that will be applied to an R01 proposal on supporting spatial navigation in older adults and those with Alzheimer?s disease and related dementias.