The cognitive and behavioral effects of prenatal alcohol exposure (PAE) have broad, lifelong impacts on individuals with a fetal alcohol spectrum disorder (FASD), with fewer than half of individuals with an FASD able to live independently as adults. Combined with the current prevalence estimates of FASD, at up to 5% of the population in the United States, this leads to considerable societal costs. Despite this disease burden, there are no pharmaceutical agents and few interventions specific to FASD. This project will facilitate forward and backward translation between animal and human models with a long-term goal of guiding development of interventions to alleviate the effects of PAE. Neural oscillations are ubiquitous in mammalian brains and are measurable using local field potentials and noninvasive measures. Using magnetoencephalography in adolescents 12-16 years of age, this clinical project will elicit neural oscillations in two cognitive tasks and rest, which have been reliably used in both rodent and human models, and assess structural connectivity using diffusion tensor imaging. We have shown previously that alpha oscillations are altered due to PAE during rest and alpha power was linked to cortico-thalamic connectivity in younger individuals with an FASD. We hypothesize that these alterations in alpha oscillations persist into adolescence and are related to cortico- thalamic connectivity as examined in Component 4 (functional connectivity) and Component 6 (structural connectivity). We have previously identified altered gamma oscillations in adolescents with an FASD in basic sensory tasks and here we hypothesize that gamma alterations will be evident during cognitive tasks and related to cognitive effects of PAE that persist into adolescence. In aim 1, we will test these hypotheses by quantifying the group differences of alpha and gamma oscillations during performance of a visual spatial working memory task, a set-shifting task, and during rest. In aim 2 we will test the underlying mechanisms related to altered neural oscillations using the Human Neocortical Neurosolver computational model designed to model noninvasive population responses measured with MEG. We hypothesize that altering cortico- thalamic model parameters will alter alpha oscillations in line with empirical findings. We further hypothesize that altering excitatory/inhibitory input parameters due to the effects of PAE on inhibitory interneurons will best match alterations in gamma oscillations measured empirically. Finally, aim 3 will examine the effects of chronic stress, often experienced by individuals with an FASD, on alpha and gamma oscillations to gain a broader understanding of how environment combines with the effects of PAE to alter brain function in adolescence. This aim will align with Component 5. This innovative project is the first to link noninvasive measures of neural oscillations to PAE preclinical studies using similar tasks, the first to apply a biophysic...