Resting-State Functional and Structural Connectivity Within an Insula-Amygdala Route Specifically Index State and Trait Anxiety

Background: Conjoint activity of the insula and amygdala has frequently been reported during emotional stimulation in general and in anxiety-related contexts in particular. However, direct connectivity between the insula and amygdala in this framework has received little attention so far. Studying whether inter-individual differences in anxiety reflect variation in insula-amygdala connectivity is a way to push forward the understanding of network-related aspects underlying anxious behavior. Methods: To investigate functional and structural connectivity, we applied resting-state functional magnetic resonance imaging and diffusion tensor imaging in a group of 32 healthy subjects. Specific measures of connectivity between subregions of the insula and amygdala were related to subjects' anxiety levels. Results: Resting-state functional connectivity between the anterior insula and the basolateral amygdala was strongly related to state anxiety, explaining 40% of behavioral variance across subjects. This was substantiated by applying tractography, yielding a relationship between trait anxiety and axial diffusivity for a direct pathway between anterior insula and basolateral amygdala. Conclusions: Our results indicate that anterior insula and basolateral amygdala constitute a network part that is prominently linked to anxiety. Within this route, state and trait behavioral impacts seem to be specifically linked to dynamic functional and more static structural neural aspects, respectively. Insula-amygdala resting-state functional connectivity can be assessed in an easy and straightforward way and has high potential to serve as a biomarker for anxiety.