The future of neuroscience in developmental psychopathology.

Developmental psychopathology started as an intersection of fields and is now a field itself. As we contemplate the future of this field, we consider the ways in which a newer, interdisciplinary field - human developmental neuroscience - can inform, and be informed by, developmental psychopathology. To do so, we outline principles of developmental psychopathology and how they are and/or can be implemented in developmental neuroscience. In turn, we highlight how the collaboration between these fields can lead to richer models and more impactful translation. In doing so, we describe the ways in which models from developmental psychopathology can enrich developmental neuroscience and future directions for developmental psychopathology.

Emotional distractors and attentional control in anxious youth: eye tracking and fMRI data.

Attentional control theory suggests that high cognitive demands impair the flexible deployment of attention control in anxious adults, particularly when paired with external threats. Extending this work to pediatric anxiety, we report two studies utilising eye tracking (Study 1) and functional magnetic resonance imaging (Study 2). Both studies use a visual search paradigm to examine anxiety-related differences in the impact of threat on attentional control at varying levels of task difficulty. In Study 1, youth ages 8-18 years (N = 109), completed the paradigm during eye tracking. Results indicated that youth with more severe anxiety took longer to fixate on and identify the target, specifically on difficult trials, compared to youth with less anxiety. However, no anxiety-related effects of emotional distraction (faces) emerged. In Study 2, a separate cohort of 8-18-year-olds (N = 72) completed a similar paradigm during fMRI. Behaviourally, youth with more severe anxiety were slower to respond on searches following non-threatening, compared to threatening, distractors, but this effect did not vary by task difficulty. The same interaction emerged in the neuroimaging analysis in the superior parietal lobule and precentral gyrus-more severe anxiety was associated with greater brain response following non-threatening distractors. Theoretical implications of these inconsistent findings are discussed.

Cued fear memory generalization increases over time.

Fear memory is a highly stable and durable form of memory, even over vast (remote) time frames. Nevertheless, some elements of fear memory can be forgotten, resulting in generalization. The purpose of this study is to determine how cued fear memory generalizes over time and measure underlying patterns of cortico-amygdala synaptic plasticity. We established generalization gradients at recent (1-d) and remote (30-d) retention intervals following auditory cued fear conditioning in adult male C57BL/6 mice. Results revealed a flattening of the generalization gradient (increased generalization) that was dissociated from contextual fear generalization, indicating a specific influence of time on cued fear memory performance. This effect reversed after a brief exposure to the novel stimulus soon after learning. Measurements from cortico-amygdala imaging of the activity-regulated cytoskeletal Arc/arg 3.1 (Arc) protein using immunohistochemistry after cued fear memory retrieval revealed a stable pattern of Arc expression in the dorsolateral amygdala, but temporally dynamic expression in the cortex. Over time, increased fear memory generalization was associated with a reduction in Arc expression in the agranular insular and infralimbic cortices while discrimination learning was associated with increased Arc expression in the prelimbic cortex. These data identify the dorsolateral amygdala, medial prefrontal, and insular cortices as loci for synaptic plasticity underlying cued fear memory generalization over time.

Chronic Ethanol During Adolescence Impacts Corticolimbic Dendritic Spines and Behavior.

BACKGROUND: Risk for alcohol use disorders (AUDs) in adulthood is linked to alcohol drinking during adolescence, but understanding of the neural and behavioral consequences of alcohol exposure during adolescence remains incomplete. Here, we examined the neurobehavioral impact of adolescent chronic intermittent EtOH (CIE) vapor exposure in mice. METHODS: C57BL/6J-background Thy1-EGFP mice were CIE-exposed during adolescence or adulthood and examined, as adults, for alterations in the density and morphology of dendritic spines in infralimbic (IL) cortex, prelimbic (PL) cortex, and basolateral amygdala (BLA). In parallel, adolescent- and adult-exposed C57BL/6J mice were tested as adults for 2-bottle EtOH drinking, sensitivity to EtOH intoxication (loss of righting reflex [LORR]), blood EtOH clearance, and measures of operant responding for food reward. RESULTS: CIE during adolescence decreased IL neuronal spine density and increased the head width of relatively wide-head IL and BLA spines, whereas CIE decreased head width of relatively narrow-head BLA spines. Adolescents had higher EtOH consumption prior to CIE than adults, while CIE during adulthood, but not adolescence, increased EtOH consumption relative to pre-CIE baseline. CIE produced a tolerance-like decrease in LORR sensitivity to EtOH challenge, irrespective of the age at which mice received CIE exposure. Mice exposed to CIE during adolescence, but not adulthood, required more sessions than AIR controls to reliably respond for food reward on a fixed-ratio (FR) 1, but not subsequent FR3, reinforcement schedule. On a progressive ratio reinforcement schedule, break point responding was higher in the adolescent- than the adult-exposed mice, regardless of CIE. Finally, footshock punishment markedly suppressed responding for reward in all groups. CONCLUSIONS: Exposure to CIE during adolescence altered dendritic spine density and morphology in IL and BLA neurons, in parallel with a limited set of behavioral alterations. Together, these data add to growing evidence that key corticolimbic circuits are vulnerable to the effects of alcohol during adolescence, with lasting, potentially detrimental, consequences for behavior.