Nothing to fear? Neural systems supporting avoidance behavior in healthy youths

Abstract

Active avoidance involving controlling and modifying threatening situations characterizes many forms of clinical pathology, particularly childhood anxiety. Presently our understanding of the neural systems supporting human avoidance is largely based on nonhuman research. Establishing the generality of nonhuman findings to healthy children is a needed first step towards advancing developmental affective neuroscience research on avoidance in childhood anxiety. Accordingly, this investigation examined brain activation patterns to threatening cues that prompted avoidance in healthy youths. During functional magnetic resonance imaging, fifteen youths (ages 9-13) completed a task that alternately required approach or avoidance behaviors. On each trial either a threatening 'Snake' cue or a 'Reward' cue advanced towards a bank containing earned points. Directional buttons enabled subjects to move cues away from (Avoidance) or towards the bank (Approach). Avoidance cues elicited activation in regions hypothesized to support avoidance in nonhumans (amygdala, insula, striatum and thalamus). Results also highlighted that avoidance response rates were positively correlated with amygdala activation and negatively correlated with insula and anterior cingulate activation. Moreover, increased amygdala activity was associated with decreased insula and anterior cingulate activity. Our results suggest that nonhuman neurophysiological research findings on avoidance may generalize to neural systems associated with avoidance in childhood. Perhaps most importantly, the amygdala/insula activation observed suggests that threat-related responses can be maintained even when aversive events are consistently avoided, which may account for the persistence of avoidance-coping in childhood anxiety. The present approach may offer developmental affective neuroscience a conceptual and methodological framework for investigating avoidance in childhood anxiety.

Figure 1. Approach-Avoidance task cues and response contingencies

The schematic reveals the general structure of approach, avoidance and control trials---see Methods for timing parameters. One cue was presented per trial and presentation order was randomized over two imaging sessions. Prior to neuroimaging, subjects learned to use two available response button to physically move cues towards (right) or away (left) from a hypothetical off-screen ‘bank’ containing their points. During presentation of a slow paced Approach cue (described as a ‘Money’ cue) all subjects advanced the cue towards the bank by repeatedly pressing a target button in order to earn points. During a fast paced Avoidance cue (described as a point-eating ‘Snake’ cue) all subjects moved the cue away from the bank by repeatedly pressing a target button in order to prevent point loss. During a slow paced control cue subjects were instructed that moving the cue in either direction was inconsequential, with correct responding producing an arbitrary symbol.

Figure 2. Regional activation to Avoidance and Approach cues

Panel A highlights activation to the avoidance cue in regions hypothesized to support nonhuman instrumental avoidance (amygdala, insula, thalamus and striatum). Plots show individual subject contrast values (avoidance parameter estimate – control parameter estimate) for avoidance in the right amygdala and insula. Panel B highlights limited activation to the cue that prompted approach behavior.

Figure 3. Correlations between activation to avoidance cue and avoidance response rates

The top plot highlights a positive correlation in the amygdala between avoidance cue activation and avoidance response rates. The remaining plots highlight negative correlations in the insula and anterior cingulate between avoidance cue activation and avoidance response rates. Similar relations were not observed for the approach cue.