This is the first study to map neural processing engaged during real-world social interactions in either anxious or healthy adolescents. Two main fMRI findings emerged. First, anxious adolescents showed greater amygdala activation than did healthy adolescents when viewing photographs of peers rated as less desirable relative to those deemed more desirable for an anticipated social interaction. Second, these differences were paralleled by differing patterns of coactivation in the amygdala-vlPFC circuitry. These findings emerged against a backdrop of behavioral findings. Compared with healthy adolescents, anxious adolescents perceived unfamiliar peers as less likely to want to chat with them, consistent with studies demonstrating that anxious youth view themselves as socially unaccepted.30
Thus, the current task replicates and adds to previous work demonstrating a cognitive bias about social evaluation in adolescent anxiety by linking this observation to measures of neural system function. Indeed, social stimuli typically considered non-threatening (ie, smiling peers) elicited robust amygdala responses only in patients, especially when viewing peers whom they had rated negatively.
Because participants were told that peers would learn of their ratings, having rated certain peers as undesirable was expected to generate particularly heightened levels of concern about evaluation in the anxious participant. However, the amygdala response to the low-desirability peers may reflect other processes as well, eg, avoidance of specific individuals or concern about the possibility of chatting with peers that the participant did not like. Further work is needed to extend the current findings to delineate the precise feature of low-desirability peers that elicits a heightened amygdala response in socially anxious adolescents. However, we documented a strong relationship between participants’ initial ratings of each peer’s desirability and later ratings of expected peer evaluation; this provides some evidence that participants’ initial impressions relate to a lasting aspect of the social-evaluative processes that can be engaged 2 weeks later. Regardless of the precise psychological context that most robustly elicits between-group differences in the adolescent amygdala response, the present findings add to prior work in both adolescents and adults. Specifically, the current and prior findings suggest that psychological interpretations initiate or maintain social information processing biases associated with neural function in anxiety disorders.11,20,22
The present study underscores the powerful role of interactions between attention and stimulus properties in shaping the amygdala response, adding to previous work. Specifically, adult social phobia also involves a pronounced amygdala response to socially threatening faces, but this heightened response occurs when attention is constrained to a nonemotional context.20,23
As in the current work, our previous research in at-risk or anxious adolescents also shows that focusing attention on disorder-relevant cognitions elicits amygdala hyperactivation.11,26
Moreover, the current study adds to these findings by showing that appraisal variations influence amygdala response even for social stimuli that prototypically appear nonthreatening. This finding again illustrates the powerful effect of viewing context as mediated by changes in attention. The lack of amygdala engagement during appraisal of peer evaluation in controls suggests that adolescents without social anxiety do not demonstrate the same cognitive biases and associated neural responses that reflect fear of social evaluation.
Amygdala-response differences were paralleled by differential amygdala-vlPFC coactivation, circuitry previously implicated in attention modulation42
and behavioral flexibility.43
These results complement prior findings in adolescents.11,13,14
As in other research,29
our measures of anxiety severity and task performance both correlated with amygdala-vlPFC connectivity. This centrally implicates perturbed amygdala-vlPFC engagement in core cognitive features of adolescent social anxiety. However, beyond our work on vlPFC engagement in adolescent anxiety, considerable research in adult humans and animal models also implicates ventral-medial PFC (vmPFC) in amygdala regulation, particularly in extinction-related processes.44–46
Accordingly, one might also expect between-group differences in vmPFC-amygdala connectivity in the current study. As noted, our prior work more consistently implicates the vlPFC than the vmPFC in adolescent anxiety. Nevertheless, because neither our prior nor our present work specifically targets extinction and related emotion-regulatory processes most consistently shown to engage vmPFC,11,13,14
the current and prior data do not firmly address questions on the role of vmPFC engagement in adolescent anxiety.
The current and prior findings in adolescent anxiety disorders suggest that distinct amygdala-vlPFC perturbations manifest in distinct psychological contexts. The vlPFC and amygdala are strongly interconnected anatomically,47
and the 2 regions can reliably be engaged by the same class of stimuli.11,25,31
However, available data also show that the vlPFC and amygdala perform different functions. For example, while the amygdala is more closely associated with controlling attention to orchestrate stimulus-reinforcement learning, vlPFC is more closely associated with stimulus-response learning, as manifest on response-reversal and flexibility tasks.43
In the context of the present task, these data suggest that vlPFC activity might reflect positive vlPFC-amygdala coupling arising from the amygdala, which signals the need to avoid an interaction and adjust behavior accordingly. In other work on attention orienting, briefly presented threats served as implicit distracters from task-related goals. In this context, negative amygdala-vlPFC connectivity occurs in healthy adolescents but not in adolescents with generalized anxiety disorder.14
This may reflect the specific effect on orienting behavior and vlPFC response that emerges when threat cues draw attention away from a competing attention-orienting task; in this instance, engagement of the vlPFC in healthy subjects in tandem with associated negative vlPFC-amygdala coupling might facilitate competent task performance by maintaining representations of task-related goals despite the presence of salient emotional distractors. Regardless, evidence of stronger positive amygdala-vlPFC connectivity or stronger vlPFC engagement in patients than controls emerges across many neuroimaging studies.11,13,22,48,49
This is consistent with data implicating amygdala-vlPFC circuitry in decision making and behavioral response where salient emotional cues appear.24
The present study has several limitations. First, the sample size is relatively small. Because results derived from small samples are associated more commonly with type II rather than type I error, the potential for masking true effects increases; however, observation of expected significant findings reduces this possibility. Nonetheless, given limitations in statistical power associated with small samples, greater caution is needed when interpreting negative rather than positive findings. Second, roughly half of the patients did not meet criteria for SP, though all reported significant concerns about social interactions. Limiting probands to those with SP could provide a more homogenous sample, reduce variance, and increase statistical power; again, this limitation is also likely to contribute more to type II than type I errors, further suggesting the need to emphasize positive more than negative findings. However, the sample selection approach did not hinder our ability to detect hypothesized group differences and a secondary analysis suggested that amygdala dysfunction might indeed occur in both SP and other adolescent anxiety disorders involving heightened social concerns. Observation of correlations among anxiety symptom ratings, task performance, and neural engagement also support this possibility. Nevertheless, an important future step will be to conduct a larger, more definitive study of participants with varying levels of social anxiety across the full range of the social anxiety continuum. This would provide vital data on key questions arising from this initial study concerning the degree to which perturbed amygdala and associated amygdala-vlPFC circuitry function in adolescent social anxiety is best viewed as a categorical or continuous construct. Third, the social evaluation task has some limitations. Task sensitivity to group differences may have been reduced because our key event incorporated 2 subcomponents rather than examining each component separately and additional “jitter” time was not interspersed between subcomponents. This limitation may have been offset by the advantages gained in task feasibility and psychological fidelity that was maintained, particularly given confirmation of expected findings. Nonetheless, future studies should attempt to separate neural response to picture presentation and to rating.
Despite these limitations, the present study has several strengths. First, the task paradigm is unique in that it engaged psychological processes central to clinical adolescent anxiety concerning social events. Moreover, our past work used photographs of adults to elicit amygdala hyperactivation to negative-valence faces,11,13,14,26
whereas the present study used positive-valence adolescent faces. Second, the present findings support theoretical models. Anxious adolescents demonstrated neural abnormalities when assessing how peers whom they rated negatively would evaluate them in return. This effect occurred despite the positive accepting cues depicted in the peers. Third, functional connectivity patterns support prior studies on circuitry encompassing the vPFC and the amygdala. Future studies may examine connectivity to add further insight on cognitive modulation of emotion and its role in cognitive-behavioral treatments. These results also inform a more precise model of the brain’s response to complex social interactions, increasing precision in attempts to understand neurophysiological and cognitive mechanisms that underlie adolescent social anxiety.