Developmental aspects of fear generalization - A MEG study on neurocognitive correlates in adolescents versus adults

Abstract

Background: Fear generalization is pivotal for the survival-promoting avoidance of potential danger, but, if too pronounced, it promotes pathological anxiety. Similar to adult patients with anxiety disorders, healthy children tend to show overgeneralized fear responses.

Objective: This study aims to investigate neuro-developmental aspects of fear generalization in adolescence - a critical age for the development of anxiety disorders.

Methods: We compared healthy adolescents (14-17 years) with healthy adults (19-34 years) regarding their fear responses towards tilted Gabor gratings (conditioned stimuli, CS; and slightly differently titled generalization stimuli, GS). In the conditioning phase, CS were paired (CS+) or remained unpaired (CS-) with an aversive stimulus (unconditioned stimuli, US). In the test phase, behavioral, peripheral and neural responses to CS and GS were captured by fear- and UCS expectancy ratings, a perceptual discrimination task, pupil dilation and source estimations of event-related magnetic fields.

Results: Closely resembling adults, adolescents showed robust generalization gradients of fear ratings, pupil dilation, and estimated neural source activity. However, in the UCS expectancy ratings, adolescents revealed shallower generalization gradients indicating overgeneralization. Moreover, adolescents showed stronger visual cortical activity after as compared to before conditioning to all stimuli.

Conclusion: Various aspects of fear learning and generalization appear to be mature in healthy adolescents. Yet, cognitive aspects might show a slower course of development.

Keywords: Adolescence; Brain development; EEG; Event-related fields; Fear conditioning; Fear generalization; MEG.

Fig. 1

Flow-chart visualizing the recruitment pathways. Note: Due to the overall high number of adolescents with dental retainers, participants with retainers were only excluded if retainers caused artifacts in the MEG signal. This was tested by means of an MEG pretest.

Fig. 2

Experimental Procedure. A. The assessment consisted of a Baseline Perceptual Midpoint (PM) Task, an MEG-Baseline phase, an MEG-Conditioning phase which terminated with a fear rating of the CS+ , the CS- and the respective audiovisual USs, an MEG-Test-Phase, which terminated with fear- and UCS expectancy ratings of the CS+ , the CS- and all GS, and – again – the PM Task. B. Sequence of stimulus presentation during the MEG Baseline, Conditioning and Test phase. Stimuli were repeatedly presented. In the Conditioning and Test phase the CS+ predicted the UCS in 33% of the cases while a warning signal predicted all UCS in the Baseline phase. Parallel to the MEG-signal pupil dilation was recorded. C. Example of stimulus set used as CS+ /- and GS (here: orientations between 11° and 35°).

Fig. 3

Subjective Ratings and Perceptual Midpoint Task. A. Fear ratings indicating subjective fear responses from 1 (no fear) to 10 (extreme fear) in response to the CS+ , CS- and the GS. B. UCS expectancy ratings indicating the perceived probability that the UCS would appear following CS+ , CS- and GS on a scale from 1 = very unlikely to 10 = very likely. C. Perceptual midpoint task. Top and middle: Relative frequencies of each GS to be classified as more similar to CS- (left side) or more similar to CS+ (right side) before (Baseline) and after (Test) the Conditioning phase, respectively. Frequencies are provided separately for adults (top) and adolescents (middle). Bottom: Test minusBaseline differences of relative frequencies. Error bars indicate 95% confidence intervals.

Fig. 4

Changes of Pupil diameter. Significant linear effects in pupil diameter as revealed by the temporal cluster permutation analysis of linear gradients. Group-independent negative effects (constriction from CS- to CS+) were observed in an early time interval (Pupil A: 13–913 ms after stimulus onset), while group-independent positive effects (dilation from CS- to CS+) were observed in a later time interval (Pupil B: 1187–1493 ms after stimulus onset, N = 74). Bar graphs show the change in pupil diameter (Test minus Baseline) for each group (adults, adolescents) within the respective time-intervals. Error bars denote 95% confidence intervals.

Fig. 5

MEG Clusters based on Linear Trend Analyses. Clusters revealing negative linear gradients (i.e., CS- > CS+) are indicated in blue (top), clusters revealing positive linear gradients (i.e., CS- < CS+) are indicated in red (bottom). Bar graphs show the regional neural activity (Test minus Baseline in nAM) in the displayed clusters. Error bars denote 95% confidence intervals. For visualization purposes, clusters based on L2-MNE topographies were projected on standard 3D brain models.