Extinction of Conditioned Fear in Adolescents and Adults: A Human fMRI Study.

Despina E Ganella,Sarah Whittle,Jee Hyun Kim,Katherine D Drummond,Eleni P Ganella

doi:10.3389/fnhum.2017.00647

Abstract

Little is known about the neural correlates of fear learning in adolescents, a population at increased risk for anxiety disorders. Healthy adolescents (mean age 16.26) and adults (mean age 29.85) completed a fear learning paradigm across two stages during functional magnetic resonance imaging (fMRI). Stage 1 involved conditioning and extinction, and stage 2 involved extinction recall, re-conditioning, followed by re-extinction. During extinction recall, we observed a higher skin conductance response to the CS+ relative to CS− in adolescents compared to adults, which was accompanied by a reduction in dorsolateral prefrontal cortex (dlPFC) activity. Relative to adults, adolescents also had significantly reduced activation in the ventromedial PFC, dlPFC, posterior cingulate cortex (PCC), and temporoparietal junction (TPJ) during extinction recall compared to late extinction. Age differences in PCC activation between late extinction and late conditioning were also observed. These results show for the first time that healthy adolescent humans show different behavioral responses, and dampened PFC activity during short-term extinction recall compared to healthy adults. We also identify the PCC and TPJ as novel regions that may be associated with impaired extinction in adolescents. Also, while adults showed significant correlations between differential SCR and BOLD activity in some brain regions during late extinction and recall, adolescents did not show any significant correlations. This study highlights adolescent-specific neural correlates of extinction, which may explain the peak in prevalence of anxiety disorders during adolescence.

Highlights

Anxiety disorders have the highest lifetime prevalence of all mental disorders (Kessler et al, 2005) and adolescence has been identified as a vulnerable period for their emergence (Merikangas et al, 2011; Polanczyk et al, 2015)
Tukey honest significant difference (HSD) multiple comparisons revealed that late conditioning was significantly different to early conditioning and late extinction (∗p’s < 0.05) (Figure 1B)
This indicates that Skin conductance response (SCR) for conditioned stimulus (CS)+ compared to CS− significantly increased by late conditioning compared to early conditioning, and it significantly decreased by late extinction

Summary

Introduction

Anxiety disorders have the highest lifetime prevalence of all mental disorders (Kessler et al, 2005) and adolescence has been identified as a vulnerable period for their emergence (Merikangas et al, 2011; Polanczyk et al, 2015). Extinction of conditioned fear is the reduction in fear shown to a fear-inducing stimulus when it has been repeatedly presented without any threatening outcome. This process is thought to underlie vulnerability to anxiety disorders, and it is the most widely used model to understand fMRI of Extinction in Youths and Adults exposure-based therapies (Milad and Quirk, 2012). We have shown that adolescent rats are impaired in extinction of a fear conditioned stimulus (CS) compared to adult rats (McCallum et al, 2010; Kim et al, 2011; Zbukvic et al, 2017). Adolescent rats fail to remember extinction when tested the day and show significantly higher levels of fear compared to older rats (i.e., adolescent rats show deficits in extinction recall), as well as compared to fear levels at the end of extinction (McCallum et al, 2010; Kim et al, 2011; Ganella et al, 2017; Zbukvic et al, 2017)

Methods

Results

Discussion

Conclusion