Objective Behavioral inhibition is an early childhood temperament recently associated with altered striatal response in adolescence to incentives of increasing magnitudes. Since early childhood behavioral inhibition is also associated with risk for adolescent social phobia, a similar pattern of striatal activation may manifest in social phobia. The present study compares striatal function in healthy adolescents, adolescents with social phobia, and adolescents with generalized anxiety disorder. Method Blood-oxygen-level-dependent signal in striatal regions was examined in 58 medication-free adolescents—14 with social phobia, 18 with generalized anxiety disorder but not social phobia, and 26 with no psychiatric disorder—matched on sex, age, puberty, IQ, and socioeconomic status. During functional magnetic resonance imaging, participants responded to incentive cues depicting potential monetary gains or losses of varying magnitudes. Results While anticipating incentives of increasing magnitude, adolescents with social phobia showed increasingly heightened caudate and putamen activation at a level greater than that seen in the healthy comparison and generalized anxiety disorder groups. The generalized anxiety disorder group showed a unique valence-specific putamen response relative to the healthy comparison or social phobia group. Both patient groups displayed more complex patterns in the nucleus accumbens than in the caudate or putamen. Conclusions Caudate and putamen hypersensitivity to incentives of increasing magnitudes characterizes adolescent social phobia, relative to activation in this region in adolescents with generalized anxiety disorder as well as healthy adolescents. Thus, these findings resemble the pattern previously found in adolescents with early childhood behavioral inhibition, thereby implicating similar neural responses to anticipation of incentives in both early childhood behavioral inhibition and adolescent social phobia.

Reward neurocircuitry links motivation with complex behavioral responses. Studies of incentive processing have repeatedly demonstrated activation of nucleus accumbens (NAc), thalamus, and anterior insula, three key components of reward neurocircuitry. The contribution of the thalamus to this circuitry in humans has been relatively ignored, a gap that needs to be filled, given the central role of this structure in processing and filtering information. This study aimed to understand how these three regions function as a network during gain or loss anticipation in adults and youth. Towards this goal, functional magnetic resonance imaging (fMRI) and dynamic causal modeling (DCM) were used to examine effective connectivity among these three nodes in healthy adults and adolescents who performed the monetary incentive delay (MID) task. Seven connectivity models, based on anatomic connections, were tested. They were estimated for incentive anticipation and underwent Bayesian Model Selection (BMS) to determine the best-fit model for each adult and adolescent group. Connection strengths were extracted from the best-fit model and examined for significance in each group. These variables were then entered into a linear mixed model to test between-group effects on effective connectivity in reward neurocircuitry. The best-fit model for both groups included all possible anatomic connections. Three main findings emerged: (1) Across the task, thalamus and insula significantly influenced NAc; (2) A broader set of significant connections was found for the loss-cue condition than the gain-cue condition in both groups; (3) Finally, between-group comparisons of connectivity strength failed to detect statistical differences, suggesting that adults and adolescents use this incentive-processing network in a similar manner. This study demonstrates the way in which the thalamus and insula influence the NAc during incentive processing in humans. Specifically, this is the first study to demonstrate in humans the key role of thalamus projections onto the NAc in support of reward processing. Our results suggest that anticipation of gain/loss involves an ‘alerting’ signal (thalamus) that converges with interoceptive information (insula) to shape action selection programs in the ventral striatum.

The present study compared blood oxygen level dependent (BOLD) response in behaviorally inhibited and behaviorally non-inhibited adolescents to positive and negative feedback following their choice in a reward task. Previous data in these same subjects showed enhanced activation in striatal areas in behaviorally inhibited subjects to cues predicting gain or a loss. However, no analyses had examined responses following actual gains or losses. Relative to non-inhibited subjects, behaviorally inhibited subjects in the current study showed enhanced caudate response to negative but not positive feedback, indicating that striatal sensitivity to feedback may be specific to aversive information. In addition, compared to non-inhibited subjects, behaviorally inhibited subjects exhibited reduced differentiation between positive and negative feedback in ventromedial prefrontal cortex (vmPFC). This suggests a perturbed ability to encode reward value.

Background Attention biases towards 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 towards 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 vs. 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.