Distinct neural signatures of threat learning in adolescents and adults

Abstract

Most teenage fears subside with age, a change that may reflect brain maturation in the service of refined fear learning. Whereas adults clearly demarcate safe situations from real dangers, attenuating fear to the former but not the latter, adolescents' immaturity in prefrontal cortex function may limit their ability to form clear-cut threat categories, allowing pervasive fears to manifest. Here we developed a discrimination learning paradigm that assesses the ability to categorize threat from safety cues to test these hypotheses on age differences in neurodevelopment. In experiment 1, we first demonstrated the capacity of this paradigm to generate threat/safety discrimination learning in both adolescents and adults. Next, in experiment 2, we used this paradigm to compare the behavioral and neural correlates of threat/safety discrimination learning in adolescents and adults using functional MRI. This second experiment yielded three sets of findings. First, when labeling threats online, adolescents reported less discrimination between threat and safety cues than adults. Second, adolescents were more likely than adults to engage early-maturing subcortical structures during threat/safety discrimination learning. Third, adults' but not adolescents' engagement of late-maturing prefrontal cortex regions correlated positively with fear ratings during threat/safety discrimination learning. These data are consistent with the role of dorsolateral regions during category learning, particularly when differences between stimuli are subtle [Miller EK, Cohen JD (2001) Annu Rev Neurosci 24:167-202]. These findings suggest that maturational differences in subcortical and prefrontal regions between adolescent and adult brains may relate to age-related differences in threat/safety discrimination. amygdala | brain development | discriminative fear conditioning | threat responding | anxiety

Teens that fear screams: A comparison of fear conditioning, extinction, and reinstatement in adolescents and adults

“…The finding that adolescents showed stronger conditioning relative to adults on the latency of first fixation to the CSþ measure is consistent with previous studies reporting elevated threat responding during adolescence (Den & Richardson, 2013;Lau et al, 2011). Specifically, in the present study, adolescents showed a decrease in the latency of first fixation to the CSþ from preacquisition to conditioning.…”

“…Although there were no differences in fear ratings of the CSþ (i.e., the threat cue that actually predicted the aversive US) between the two age groups, adolescents had higher fear ratings to the CSÀ (i.e., the safety cue that did not predict the aversive US) than did the adults. Lau et al (2011) concluded that overgeneralization of fear from the CSþ to the CSÀ in adolescents was driven by greater subcortical relative to cortical activity, providing support for the "imbalance" model.…”

Sensitive Periods in Affective Development: Nonlinear Maturation of Fear Learning

“…Children as young as 3 years show evidence of fear acquisition (Gao et al, 2010), with discrimination between an aversively conditioned and a neutral stimulus (CS þ 4CS À ) improving with age (Gao et al, 2010;Glenn et al, 2012). This increased discrimination ability with age continues into adulthood, and is associated with distinct developmental patterns of neural activity during fear learning (Lau et al, 2011). Consistent developmental changes in fear extinction learning have been observed across species.…”

Evaluating differences in Pavlovian fear acquisition and extinction as predictors of outcome from cognitive behavioural therapy for anxious children

“…Similar to findings in anxious adults (e.g., Michael, Blechert, Vriends, Margraf, & Wilhelm, 2007;Orr et al, 2000;Peri, Ben-Shakhar, Orr, & Shalev, 2000), experimental studies have found that anxious, relative to nonanxious, youth show larger physiological responses particularly during initial trials of extinction, and more negative evaluations of the CS+ than the CSÀ, as well as larger responses overall to both CSs (e.g., Craske et al, 2008;Jovanovic et al, 2014;Lau et al, 2008Lau et al, , 2011Liberman, Lipp, Spence, & March, 2006;Waters, Henry, & Neumann, 2009). If CBT reduces fear via extinction principles during exposure therapy (Vervliet et al, 2013), then individual differences during extinction trials may predict response to CBT.…”