Acute stress shifts the brain into a state that fosters rapid defense mechanisms. Stress-related neuromodulators are thought to trigger this change by altering properties of large-scale neural populations throughout the brain. We investigated this brain-state shift in humans. During exposure to a fear-related acute stressor, responsiveness and interconnectivity within a network including cortical (frontoinsular, dorsal anterior cingulate, inferotemporal, and temporoparietal) and subcortical (amygdala, thalamus, hypothalamus, and midbrain) regions increased as a function of stress response magnitudes. β-adrenergic receptor blockade, but not cortisol synthesis inhibition, diminished this increase. Thus, our findings reveal that noradrenergic activation during acute stress results in prolonged coupling within a distributed network that integrates information exchange between regions involved in autonomic-neuroendocrine control and vigilant attentional reorienting.

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Background Early childhood anxiety has been linked to an increased risk for developing mood and anxiety disorders. Little, however, is known about its effect on the brain during early childhood – a period when anxiety-related traits begin to be reliably identifiable. Even less is known about the neurodevelopmental origins of individual differences in childhood anxiety. Methods We combined structural and functional magnetic resonance imaging (fMRI) with neuropsychological assessment of anxiety based on daily life experiences to investigate the effects of anxiety on the brain in seventy-six young children. We then used machine learning algorithms with balanced cross-validation to examine brain-based predictors of individual differences in childhood anxiety. Results Even in children as young as ages 7–9, high childhood anxiety is associated with enlarged amygdala volume and this enlargement is localized specifically to the basolateral amygdala. High childhood anxiety is also associated with increased connectivity between the amygdala and distributed brain systems involved in attention, emotion perception and regulation, and these effects are most prominent effect in basolateral amygdala. Critically, machine learning algorithms revealed that levels of childhood anxiety could be reliably predicted by amygdala morphometry and intrinsic functional connectivity, with the left basolateral amygdala emerging again as the strongest predictor. Conclusions Individual differences in anxiety can be reliably detected with high predictive value in amygdala-centric emotion circuits at a surprisingly young age. Our study provides important new insights into the neurodevelopmental origins of anxiety, and has significant implications for the development of predictive biomarkers to identify children at-risk for anxiety disorders.

The importance of the hippocampal system for rapid learning and memory is well recognized, but its contributions to a cardinal feature of children's cognitive development – the transition from procedure-based to memory-based problem solving strategies – are unknown. Here we show that the hippocampal system is pivotal to this strategic transition. Longitudinal fMRI in children, ages 7 to 9, revealed that the transition from use of counting to memory-based retrieval parallels increased hippocampal and decreased prefrontal-parietal engagement during arithmetic problem solving. Critically, longitudinal improvements in retrieval strategy use were predicted by increased hippocampal-neocortical functional connectivity. Beyond childhood, retrieval strategy use continued to improve through adolescence into adulthood, and was associated with decreased activation but more stable inter-problem representations in the hippocampus. Our findings provide novel insights into the dynamic role of the hippocampus in the maturation of memory-based problem solving, and establish a critical link between hippocampal-neocortical reorganization and children's cognitive development.