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.