Isolating neural components of threat bias in pediatric anxiety

Abstract

Background: Attention biases toward threat are often detected in individuals with anxiety disorders. Threat biases can be measured experimentally through dot-probe paradigms, in which individuals detect a probe following a stimulus pair including a threat. On these tasks, individuals with anxiety tend to detect probes that occur in a location previously occupied by a threat (i.e., congruent) faster than when opposite threats (i.e., incongruent). In pediatric anxiety disorders, dot-probe paradigms detect abnormal attention biases toward threat and abnormal ventrolateral prefrontal cortex (vlPFC) function. However, it remains unclear if this aberrant vlPFC activation occurs while subjects process threats (e.g., angry faces) or, alternatively, while they process and respond to probes. This magnetoencephalography (MEG) study was designed to answer this question.

Methods: Adolescents with either generalized anxiety disorder (GAD, n = 17) or no psychiatric diagnosis (n = 25) performed a dot-probe task involving angry and neutral faces while MEG data were collected. Synthetic Aperture Magnetometry (SAM) beamformer technique was used to determine whether there were group differences in power ratios while subjects processed threats (i.e., angry vs. neutral faces) or when subjects responded to incongruent versus. congruent probes.

Results: Group differences in vlPFC activation during the response period emerged with a 1-30 Hz frequency band. No group differences in vlPFC activation were detected in response to angry-face cues.

Conclusions: In the dot-probe task, anxiety-related perturbations in vlPFC activation reflect abnormal attention control when responding to behaviorally relevant probes, but not to angry faces. Given that motor responses to these probes are used to calculate threat bias, this study provides insight into the pathophysiology reflected in this commonly used marker of anxiety. In addition, this finding may inform the development of novel anxiety-disorder treatments targeting the vlPFC to enhance attention control to task-relevant demands.

Figure 1

Dot-probe paradigm and time period definitions. In dot-probe trials, participants view a fixation cross (500 ms). Then, two facial expressions of a single individual appear (500 ms). Following the face pair, a dot-probe appears (200 ms) and participants indicate via button press the orientation of the dot probe, horizontal (..) or vertical (:). A 1300 ms inter-stimulus interval separates trials. Two trial types, are used to assess attention bias (incongruent vs. congruent). In congruent trials, the dot probe appears in the same location that the emotional face (e.g., angry) had previously appeared. In incongruent trials, the dot probe appears in the opposite location. For the oscillatory power analysis, face presentation (red/dark gray arrow), response (blue/light gray arrow), and baseline control periods (black arrows) were examined. A 500 ms face presentation and a1000 ms response period served as active periods. Active periods and corresponding baseline periods were of equal length.

Figure 2

Correlations between trait anxiety measures, threat bias and vlPFC power. (a) Across both groups, Spielberger State Trait Anxiety Inventory-Children (STAI) trait anxiety scores were negatively correlated with threat bias [R=−0.35, p<0.03]. No group differences in the correlation were noted [p>0.5, patient: R=−0.30, p>0.3; healthy adolescents: R=−0.49, p<0.02]. (b) The correlation between trait anxiety and vlPFC activation during the response period for threat bias contrast was significantly different between groups [Fisher’s r-to-Z=−2.05, p<0.05]. Trait anxiety negatively correlated with vlPFC activation only in the healthy group [patient: R=0.23, p>0.4, healthy: R=−0.44, p<0.04].

Figure 3

Between-group difference in oscillatory power during response period of threat bias In the 1-30 Hz frequency band, compared with healthy adolescents, adolescents with generalized anxiety disorder exhibited greater negative power in ventrolateral prefrontal cortex (vlPFC, [(28,20,−8), t=−3.17, k=10; (35,34,−8), t=−3.13, k=5]) during the response period between incongruent and congruent conditions. Significance was detected using p<0.005 threshold and cluster size k>4, approximating a p<0.05 False Discovery Rate correction. For illustrative purposes, the graph represents extracted normalized power values in the functionally-defined vlPFC cluster highlighted by the crosshairs. Left-Posterior-Inferior coordinates reported. t=t-score, k=cluster size.