Altered Development of Amygdala-Anterior Cingulate Cortex Connectivity in Anxious Youth and Young Adults

Abstract

Background Development of cortico-amygdala circuitry underlies the maturation of emotion processing and regulation, and age-related changes in amygdala connectivity with anterior cingulate cortex (ACC) have been shown to mediate normative developmental decreases in anxiety. It remains unclear whether developmental changes in this circuitry relate to pathological anxiety in youth. The current functional magnetic resonance imaging (fMRI) study addresses this question by examining amygdala functional connectivity in anxious and healthy individuals spanning the developmental period from childhood through adulthood. Methods Youth and young adults (age 7–25) with current anxiety disorders (n=57) and healthy comparisons (n=61) completed an fMRI emotional face processing task known to elicit amygdala activation in youth and adults. We examined interaction effects of anxiety group and age on amygdala connectivity with frontolimbic regions during processing of happy, angry, and fearful faces. Results Anxiety interacted with age to predict amygdala-ACC connectivity across emotional faces. Among healthy comparisons, age was negatively related to connectivity. In contrast, age was positively associated with amygdala-ACC connectivity in the anxious group. Group effects were also observed on amygdala connectivity with midcingulate and middle frontal gyri. Effects of anxiety and age on amygdala activation were not significant. Conclusions Results indicate that anxiety is characterized by altered patterns of age-related changes in amygdala connectivity during emotional face processing. Positive associations between age and amygdala-ACC connectivity among anxious youth and young adults may indicate failure to establish early bottom-up connections in childhood and/or less top-down regulation of the amygdala into adulthood.

Development of White Matter Microstructure and Intrinsic Functional Connectivity Between the Amygdala and Ventromedial Prefrontal Cortex: Associations With Anxiety and Depression

“…These findings suggest that a lack of developmental decrease in neural connectivity between CM amygdala and rACC associated with increases in anxiety and depression traits. In support of these findings, task-based neuroimaging studies of emotional face processing show a shift from positive to negative connectivity in amygdala fronto-limbic circuits during typical development (109); young adults with anxiety fail to show this change, suggesting that an altered pattern of age-associated changes in amygdala connectivity is associated with increased anxiety(110). Intriguingly, higher amygdala-vmPFC connectivity has been associated with anxiety in typically developing 7–9 years olds (50); however, the effects were strongest in the BL amygdala, not the CM amygdala.…”

Neural correlates of explicit and implicit emotion processing in relation to treatment response in pediatric anxiety

“…Alternatively, there may be differences in the direction of ACC activation depending on age and development. For example, recent work suggests that anxiety is characterized by altered developmental patterns of amygdala connectivity with ACC from childhood into young adulthood (Kujawa, Wu, et al., ). In addition, a separate study shows that age moderates the link between anxiety and the error‐related negativity, an event‐related potential component that is generated in the ACC (Meyer, Weinberg, Klein, & Hajcak, ).…”

Biological Aging in Childhood and Adolescence Following Experiences of Threat and Deprivation: A Systematic Review and Meta-Analysis

“…One possibility is that amygdala-PFC functional connectivity is not a reliable marker of neural development. Unlike cortical thickness which has been studied widely across large representative samples (for review see Vijayakumar et al, 2016), research documenting amygdala-PFC connectivity as a marker of maturation is more modest Kujawa et al, 2016;Silvers, Insel, et al, 2016b;Wu et al, 2016), and to our knowledge, all of the studies that have demonstrated a developmental shift in this circuit have been crosssectional. As such, amygdala-mPFC connectivity may be an unreliable marker of neural maturation.…”