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Comparing neural correlates of conditioned inhibition between children with and without anxiety disorders - A preliminary study.

ABSTRACT: Cognitive-behavioral therapy (CBT), a first-line treatment for pediatric anxiety disorders, is based on principles of threat learning and extinction. However, CBT does not work sufficiently for up to 40% of clinically anxious youth. The neural and behavioral correlates of conditioned inhibition might provide promising targets for attempts to improve CBT response. During conditioned inhibition, threat and safety cues appear together, forming a safety compound. Here, we test whether this safety compound elicits a reduced fear response compared to pairing the threat cue with a novel cue (novel compound). The current pilot study compares behavioral, physiological, and neural correlates of conditioned inhibition between children with (n = 17, M_age = 13.09, SD_age = 3.05) and without (n = 18, M_age = 14.49, SD_age = 2.38) anxiety disorders. Behavioral and physiological measures did not differ between children with and without anxiety disorders during fear acquisition. During testing, children with anxiety disorders showed overall higher skin conductance response and expected to hear the aversive sound following the novel compound more often than children without anxiety disorders. Children with anxiety disorders showed more activity in the right ventromedial prefrontal cortex (vmPFC) to the safety versus novel compound. Children without anxiety disorders showed the opposite pattern - more right vmPFC activity to the novel versus safety compound (F(1,31) = 5.40, p = 0.03). No group differences manifested within the amygdala, dorsal anterior cingulate cortex, or hippocampus. These pilot findings suggest a feasible approach for examining conditioned inhibition in pediatric anxiety disorders. If replicated in larger samples, findings may implicate perturbed conditioned inhibition in pediatric anxiety disorders and provide targets for CBT.

SUBMITTER: Harrewijn A

PROVIDER: S-EPMC7855938 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Empathy is characterized by the ability to understand and share an emotional experience with another person and is closely tied to compassion and concern for others. Consequently, this increased emotional awareness and sensitivity may also be related to increased anxiety. Taken from another perspective, higher general anxiety may translate into increased concern for others, or concern for how one's actions might affect others, and therefore may be linked to increased empathy. Furthermore, self-reflection is positively related to perspective-taking and empathic concern, while rumination is closely tied to anxiety, thus providing an additional connecting point between empathy and anxiety through enhanced internally generated thought. While previous literature suggests a relationship between empathy and anxiety, this has yet to be empirically studied using neuroimaging tools aimed at investigating the underlying neural correlates that may support these convergent responses. We therefore conducted an functional magnetic resonance imaging (fMRI) study (N = 49) in which participants viewed fearful and neutral human faces and rated how the faces made them feel, to promote introspection. Participants also completed questionnaires assessing empathy Toronto Empathy Questionnaire (TEQ), trait anxiety State Trait Anxiety Inventory (STAI), worry Penn State Worry Questionnaire (PSWQ) and rumination Ruminative Responses Scale (RRS). Behaviorally, empathy positively correlated with worry, worry and rumination positively correlated with anxiety, and significant indirect relationships were found between empathy and anxiety through worry and rumination. Using the neuroimaging face processing task as a backdrop on which the neurobiological mechanisms of empathy and anxiety may interact, regressions of questionnaires with brain activations revealed that empathy related to activation in the temporoparietal junction (TPJ), anxiety related to bilateral insula activation, and worry related to medial prefrontal cortex (mPFC) activation, while rumination showed increased engagement of all three aforementioned regions. Functional connectivity (FC) analyses showed increased communication between the left amygdala and insula related to higher empathy, worry and rumination. Finally, whole-brain analysis using median split groups from questionnaires revealed that the lower halves of anxiety, worry and rumination exhibited increased activation in top-down attentional networks. In sum, empathy, worry and rumination related to enhanced bottom-up processing, while worry, rumination and anxiety exhibited decreased top-down attentional control, suggesting an indirect relationship between empathy and anxiety through the ruminative tendencies of worry.

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Comparing neural correlates of conditioned inhibition between children with and without anxiety disorders - A preliminary study.

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