Disruptions in fear-extinction learning are centrally implicated in a range of stress-related disorders, including anxiety and posttraumatic stress disorder. Given that these disorders frequently begin in childhood/adolescence, an understanding of fear-extinction learning in children is essential for (1) detecting the source of developmental susceptibility, (2) identifying mechanisms leading to pathology, and (3) informing the development and/or more judicious application of treatments for youth. Here, we offer and validate a novel virtual reality paradigm to study threat-related learning and extinction in children that models real-world cues, environments, and fear-inducing events that children are likely to experience, and are linked to the development of fear- and stress-related pathologies. We found that our paradigm is well tolerated in children as young as 6 years, that children show intact fear and extinction learning, and show evidence of divergence in subjective, physiological, and behavioral measures of conditioned fear. The paradigm is available for use in 3-D and in 2-D (e.g., for the MRI scanner) upon request at www.tnp2lab.org.
Introduction:Adequate sleep is essential for cognitive and emotion-related functioning, and 9 to 12 hr of sleep is recommended for children ages 6 to 12 years and 8 to 10 hr for children ages 13 to 18 years. However, national survey data indicate that older youth sleep for fewer hours and fall asleep later than younger youth. This shift in sleep duration and timing corresponds with a sharp increase in onset of emotion-related problems (e.g., anxiety, depression) during adolescence. Given that both sleep duration and timing have been linked to emotion-related outcomes, the present study tests the effects of sleep duration and timing, and their interaction, on resting-state functional connectivity (RS-FC) of corticolimbic emotion-related neural circuitry in children and adolescents.Methods:A total of 63 children and adolescents (6–17 years, 34 females) completed a weekend overnight sleep journal and a 10-min resting-state functional magnetic resonance imaging scan the next day (Sunday). Whole-brain RS-FC of the amygdala was computed, and the effects of sleep duration, timing (i.e., midpoint of sleep), and their interaction were explored using regression analyses.Results:Overall, we found that older youth tended to sleep later and for fewer hours than younger youth. Controlling for age, shorter sleep duration was associated with lower RS-FC between the amygdala and regions implicated in emotion regulation, including ventral anterior cingulate cortex, precentral gyrus, and superior temporal gyrus. Interestingly, midpoint of sleep was associated with altered connectivity in a distinct set of brain regions involved in interoception and sensory processing, including insula, supramarginal gyrus, and postcentral gyrus. Our data also indicate widespread interactive effects of sleep duration and midpoint on brain regions implicated in emotion regulation, sensory processing, and motor control.Conclusion:These results suggest that both sleep duration and midpoint of sleep are associated with next-day RS-FC within corticolimbic emotion-related neural circuitry in children and adolescents. The observed interactive effects of sleep duration and timing on RS-FC may reflect how homeostatic and circadian process interact in the brain and explain the complex patterns observed with respect to emotional health when considering sleep duration and timing. Sleep-related changes in corticolimbic circuitry may contribute to the onset of emotion-related problems during adolescence.
Background: In healthy adults, successful between-session recall of extinction learning depends on the hippocampus and ventromedial prefrontal cortex (vmPFC), especially when tested in the extinction context. Poor extinction recall and dysfunction within hippocampal-vmPFC circuitry are associated with fear-based disorders (e.g., anxiety, posttraumatic stress disorder). Despite the early age of onset of virtually all fear-based disorders and the protracted development of the hippocampus and vmPFC across the first two decades of life, little is known about extinction recall and the underlying neural correlates in children. Methods: Here, we tested extinction recall in 43 pre-adolescent children (ages 6–11 yrs) by coupling functional magnetic resonance imaging and virtual reality with a novel interpersonal threat-related two-day (ABBA) fear-extinction paradigm. Conditioned fear responding was assessed at behavioral, subjective, physiological, and neural levels. Results: Although children demonstrated intact within-session extinction, there was poor between-session recall of extinction learning (retention index: 13.56%), evidenced by elevations in skin conductance, avoidant behavioral responses, and subjective ratings. Elevations in conditioning fear responding were accompanied by activation in the hippocampus and insula, and increased connectivity of the hippocampus with the insula and dorsal anterior cingulate cortex - regions implicated in the return of fear in adult studies. Children who kept more distance from the extinguished cue during extinction subsequently demonstrated heightened hippocampal-cingulate coupling during recall, suggesting that avoidant behavior interferes with extinction retention. Conclusions: Poor extinction recall in children may have implications for developmental vulnerability to fear-based disorders, and for the application of therapeutic strategies that rely on principles of extinction (e.g., exposure therapy) to pediatric samples.
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