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

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

Despina E Ganella et al. Front Hum Neurosci.

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.

Keywords: adolescence; behavior therapy; fear; memory; prefrontal cortex.

Figures

Figure 1
Figure 1
Outline of the behavioral paradigm and corresponding skin conductance response data. (A) A schema of the behavioral paradigm: conditioning, extinction, recall, re-conditioning and re-extinction. Face stimuli are from NimStim set of facial expressions http://www.macbrain.org/resources.htm with the permission to publish these stimuli. (B) Skin conductance response (SCR) for adults and adolescents during the functional magnetic resonance imaging paradigm (fMRI). Stage 1 - conditioning and extinction; late conditioning was significantly different to early conditioning and late extinction (*ps < 0.05). Stage 2 - recall, re-conditioning and re-extinction; there was a significant age effect with adolescents showing more SCR compared to adults (**p < 0.0001). CS, conditioned stimulus.
Figure 2
Figure 2
Recall contrast. Adults showed significantly greater activation in the (A) dorsolateral prefrontal cortex (dlPFC) and (B) posterior cingulate cortex (PCC) compared to adolescents during the recall phase (CS+ > CS−). Post-hoc tests identified significant differences between CS+ and CS− at each phase for each age in dlPFC and PCC (*ps < 0.05). Graph generated from BOLD signal from a 6 mm sphere around the peak coordinates of the significant cluster.
Figure 3
Figure 3
Recall vs. late extinction contrast. Adults showed significantly greater activation in the (A) dorsolateral prefrontal cortex (dlPFC), (B) ventromedial prefrontal cortex (vmPFC), (C) posterior cingulate cortex (PCC), and (D) temporoparietal junction (TPJ) compared to adolescents during the recall phase (CS+ > CS−) vs. late extinction (CS+ > CS−). In these brain regions, post-hoc tests identified significant differences between CS+ and CS− within recall phase in each age group (*ps < 0.05). In PCC and TPJ, CS+ and CS− activation was also significantly different during late extinction for adolescents (*ps < 0.05). Graph generated from BOLD signal from a 6 mm sphere around the peak coordinates of the significant cluster. Arrows highlight the vmPFC and PCC regions.
Figure 4
Figure 4
Early extinction vs. early conditioning contrast and late conditioning vs. late extinction contrast findings. (A) Early extinction vs. early conditioning contrast. Adolescents showed significantly greater activation in the ventromedial prefrontal cortex (vmPFC) compared to adults during early extinction (CS+ > CS−) vs. early conditioning (CS+ > CS−). Post-hoc tests identified a significant difference between CS+ and CS−, in adolescents during early conditioning (*p < 0.05). (B) Late conditioning vs. late extinction contrast. Adolescents showed significantly greater activation in the posterior cingulate cortex (PCC) compared to adults during late extinction (CS+ > CS−) compared to late conditioning (CS+ > CS−). Graphs generated from BOLD signal from a 6 mm sphere around the peak coordinates of the significant cluster.
Figure 5
Figure 5
Correlations between brain activity and skin conductance response. (A) During late extinction, ventromedial PFC (vmPFC) activity negatively correlates with skin condutance response (SCR) in adult but not in adolescent participants (Adults r = −0.63; Adolescents r = 0.19). (B) Posterior cingulate cortex (PCC) activity during late extinction negatively correlates with SCR in adult but not in adolescent participants (Adults r = −0.62; Adolescents r = −0.144). (C) Dorsolateral prefrontal cortex (dlPFC) activity during recall positively correlates with SCR during recall in adult but not in adolescent participants (Adults r = 0.64; Adolescents r = 0.36). *Indicates a significant correlation p < 0.05.

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