Aberrant Effective Connectivity of the Right Anterior Insula in Primary Insomnia

Objective: Daytime cognitive impairment is an essential symptom of primary insomnia (PI). However, the underlying neural substrate remains largely unknown. Many studies have shown that the right anterior insula (rAI) as a key node of salience network (SN) plays a critical role in switching between the executive control network (ECN) and the default mode network (DMN) for better performance of cognitively demanding tasks. Aberrant effective connectivity (directional functional connectivity) of rAI with ECN or DMN may be one reason for daytime cognitive impairment in PI patients. Up to now, no effective connectivity study has been conducted on patients with PI during resting-state. Our aim is to investigate the effective connectivity between the rAI and the other voxels in the whole brain in PI. Materials and Methods: Fifty drug-naive patients with PI and 40 age- and sex-matched healthy controls were scanned using resting-state functional MRI. Seed-based Granger causality analysis was used to examine effective connectivity between the rAI, including ventral and dorsal part, and the whole brain. The effective connectivity was compared between the two groups and was correlated with clinical characteristics. Results: Compared with controls, patients showed decreased effective connectivity from the rAI to the bilateral precuneus, the left postcentral gyrus (extending to bilateral precuneus) and the bilateral cerebellum posterior lobe, and decreased effective connectivity from the bilateral orbitofrontal cortex (OFC) to the rAI (single voxel P< 0.001, AlphaSim corrected with P < 0.01). Additionally, effective connectivity from the ventral rAI to the left postcentral gyrus and from the left OFC to the ventral rAI were significantly negatively correlated with Insomnia Severity Index scores (r = -0.28, P = 0.046 and r = -0.29, P = 0.038 respectively). Conclusion: The present study is the first to reveal aberrant effective connectivity between the SN hub (rAI) and the posterior DMN hub (precuneus) as well as decision-making region (OFC) and sensori-motor region in PI. These findings suggest an aberrant salience processing system of the rAI in PI patients.