UC Irvine

Decades of research have investigated the impact of the quantity and quality of maternal care on the development of healthy cognitive and emotional function in both human and rodent offspring. Emerging from this literature is the notion that the (un)predictability of maternal signals in early infancy is an important factor influencing the development of these systems. In animal models, exposure to unpredictable patterns of maternal behavior alters brain circuit maturation and cognitive and emotional outcomes, including impaired memory performance and anhedonia (the loss of pleasure or lack of reactivity to pleasurable stimuli). However, whether exposure to such signals in humans alters the development of brain pathways is unknown. In Chapter 2 of this Dissertation, in mother–child dyads, we tested the hypothesis that exposure to unpredictable maternal signals in infancy is associated with aberrant maturation of corticolimbic pathways. We focused on the uncinate fasciculus, the primary fiber bundle connecting the amygdala to the orbitofrontal cortex and a key component of the medial temporal lobe–prefrontal cortex circuit. Using high angular resolution diffusion imaging, we discovered that higher maternal unpredictability during infancy was associated with greater uncinate fasciculus generalized fractional anisotropy (a correlate of fractional anisotropy with distinct advantages). In a separate experiment, Chapter 3 of this Dissertation tested the hypothesized role of the uncinate fasciculus in adjudicating between competing memory representations at retrieval. Using multimodal imaging, we discovered that greater uncinate fasciculus integrity is associated with reduced hippocampal dentate and CA3 activity during correct discrimination of similar emotional stimuli. Together, this work yields novel insight into neurobiological mechanisms of vulnerability to cognitive deficits and advances our knowledge of the function of medial prefrontal white matter connectivity with the temporal lobe.