Multimodal imaging of prenatal alcohol exposure: Mechanisms underlying spatial navigation memory deficits in children and adolescents

Project Summary/Abstract Exposure to alcohol during prenatal brain development, perturbs hippocampal development and results in lifelong cognitive deficits in spatial memory. While rodent models have characterized cellular and synaptic changes produced by prenatal alcohol exposure (PAE), the neurophysiological mechanisms in humans remains poorly understood. There is a critical need to identify neural circuitry and brain dynamics involved in spatial memory deficits in humans. Determining the neural mechanisms underlying spatial memory deficits in children with PAE will provide foundational knowledge on how PAE alters brain function and a novel scientific framework allowing for the identification of potential treatments and interventions. Previous studies have shown that hippocampal-entorhinal circuits play critical roles in the encoding of spatial memories, while sharp-wave ripples are oscillatory events that propagate between regions to produce memory consolidation. This proposal aims to significantly advance our understanding of the neurophysiological oscillatory and dynamic changes that occur following PAE. We will conduct a multimodal neuroimaging study (fMRI and MEG) of N=112 participants between ages 8-14 years old indexing spatial navigation memory. Our overarching hypothesis is that PAE deficits to spatial memory are a consequence of a loss of hippocampal circuitry and perturbed theta-gamma oscillations. The reduction in neural oscillations will be predictive of spatial memory impairment following PAE. In Aim 1 we will examine theta oscillations within hippocampal and parahippocampal regions following encoding of spatial navigation memory to determine the temporal characteristics of spatial deficits in children with PAE. In Aim 2 we will examine gamma oscillations within prefrontal cortices following navigational breaks to determine the temporal characteristics of early memory consolidation deficits in children with PAE. In Aim 3 we will we will determine if children with PAE recruit appropriate task-dependent neural circuits during hidden platform spatial navigation. This multimodal neuroimaging study uses an ecologically valid paradigm that is highly innovative and the complementary tools could identify key mechanisms underlying neurocognitive deficits in children and adolescents with PAE. In line with the Katz Early Stage Investigator mechanism- using fMRI and multimodal data fusion of fMRI and MEG to examine spatial memory is a new research direction for the PI; the project leverages her skills in developmental neuroimaging with MEG and research examining the long- term consequences of PAE.