Abnormal Functional Connectivity of Anterior Cingulate Cortex in Patients With Primary Insomnia: A Resting-State Functional Magnetic Resonance Imaging Study

Chao-Qun Yan, Cun-Zhi Liu, Xu Wang, Jian-Wei Huo, Ping Zhou, Shuai Zhang, Qing-Nan Fu, Jie Zhang, Zhong-Yan Wang, Qing-Quan Liu

Background: Recently, there have been many reports about abnormalities regarding structural and functional brain connectivity of the patients with primary insomnia. However, the alterations in functional interaction between the left and right cerebral hemispheres have not been well understood. The resting-state fMRI approach, which reveals spontaneous neural fluctuations in blood-oxygen-level-dependent signals, offers a method to quantify functional interactions between the hemispheres directly. Methods: We compared interhemispheric functional connectivity (FC) between 26 patients with primary insomnia (48.85 ± 12.02 years) and 28 healthy controls (49.07 ± 11.81 years) using a voxel-mirrored homotopic connectivity (VMHC) method. The patients with primary insomnia and healthy controls were matched for age, gender, and education. Brain regions, which had significant differences in VMHC maps between the primary insomnia and healthy control groups, were defined as seed region of interests. A seed-based approach was further used to reveal significant differences of FC between the seeds and the whole contralateral hemisphere. Results: The patients with primary insomnia showed higher VMHC than healthy controls in the anterior cingulate cortex (ACC) bilaterally. The seed-based analyses demonstrated increased FC between the left ACC and right thalamus (and the right ACC and left orbitofrontal cortex) in patients with primary insomnia, revealing abnormal connectivity between the two cerebral hemispheres. The VMHC values in the ACC were positively correlated with the time to fall asleep and Self-Rating Depression Scale scores (SDS). Conclusions: The results demonstrate that there is abnormal interhemispheric resting-state FC in the brain regions of patients with primary insomnia, especially in the ACC. Our finding demonstrates valid evidence that the ACC is an area of interest in the neurobiology of primary insomnia.