Emotion reactivity-related brain network analysis in generalized anxiety disorder: a task fMRI study

Generalized anxiety disorder (GAD) is closely associated with emotional dysregulation. Patients with GAD tend to overreact to emotional stimuli and are impaired in emotional regulation. Using emotional regulation task, studies have found hypo-activation in prefrontal cortex (PFC) of GAD patients and concluded with inadequate top-down control. However, results remain inconsistent concerning PFC and limbic area's reactivity to emotional stimuli. What's more, only a few studies aim to identify how limbic area interacts with PFC in GAD patients. The current study aims to identify the difference in PFC-limbic circuitry response to emotional stimuli between GAD patients and healthy controls (HCs) from the perspective of brain network. Through brain network analysis, it revealed the connectivity between limbic area and PFC, and moreover, the orientation of connectivity, all of which gave a better test of inadequate top-down control hypothesis.

During fMRI scanning, participants were required to complete an emotional face identification task (fearful, neutral, happy facial expression). 30 participants (16 GAD patients, 14 HCs) were included in the formal analysis. A Bayesian-network based method was used to identify the brain network consisting of several pre-hypothesized regions of interest (ROIs) under each condition (negative, positive, neutral). In total, six graphs were obtained. Each of them represented the brain network that was common to the group under corresponding condition.

Results revealed that GAD patients showed more bottom-up connection but less top-down connection regardless of condition, relative to HCs. Also, the insula was more connected but the amygdala was less connected regardless of condition, relative to HCs. the results also revealed a very different brain network response between GAD patients and HCs even under neutral condition.

More bottom-up connection but less top-down connection may indicate that GAD patients are insufficient in top-down control, in keeping with inadequate top-down control hypothesis. The more connected insula may indicate GAD patients' abnormality in interoception processing. Relative to HCs, distinct brain network response pattern in GAD patients under neutral condition suggests GAD patients' abnormality in distinguishing safety from threat and intolerance of uncertainty.