Abnormal Functional Connectivity Intra- and Inter-Network in Resting-State Brain Networks of Patients with Toothache

Yuping Zhu,1 Xunfu Lai,1 Mengting Wang,2 Xin Tang,1 Tianyi Wan,3 Bin Li,1 Xiaoming Liu,1 Jialin Wu,1 Lei He,1 Yulin He1 1Department of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Department of Radiology, Yichang Central People’s Hospital, Yichang, People’s Republic of China; 3Department of Radiology, Jiangxi Provincial People’s Hospital, Nanchang, People’s Republic of ChinaCorrespondence: Yulin He, Department of Radiology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86 0791 8869 3802, Email ndyfy02171@ncu.edu.cnObjective: To separate the resting-state network of patients with dental pain using independent component analysis (ICA) and analyze abnormal changes in functional connectivity within as well as between the networks.Patients and Methods: Twenty-three patients with dental pain and 30 healthy controls participated in this study. We extracted the resting-state functional network components of both using ICA. Functional connectivity differences within 14 resting-state brain networks were analyzed at the voxel level. Directional interactions between networks were analyzed using Granger causality analysis. Subsequently, functional connectivity values and causal coefficients were assessed for correlations with clinical parameters.Results: Compared to healthy controls, we found enhanced functional connectivity in the left superior temporal gyrus of anterior protrusion network and the right Rolandic operculum of auditory network in patients with dental pain (p< 0.01 and cluster-level p< 0.05, Gaussian random field corrected). In contrast, functional connectivity of the right precuneus in the precuneus network was reduced, and were significantly as well as negatively correlated to those of the Visual Analogue Scale (r=− 4.93, p=0.017), Hamilton Anxiety Scale (r=− 0.46, p=0.027), and Hamilton Depression Scale (r=− 0.563, p< 0.01), using the Spearman correlation analysis. Regarding the causal relationship between resting-state brain networks, we found increased connectivity from the language network to the precuneus in patients with dental pain (p< 0.05, false discovery rate corrected). However, the increase in causal coefficients from the verbal network to the precuneus network was independent of clinical parameters.Conclusion: Patients with toothache exhibited abnormal functional changes in cognitive-emotion-related brain networks, such as the salience, auditory, and precuneus networks, thereby offering a new imaging basis for understanding central neural mechanisms in dental pain patients.Keywords: toothache, independent component analysis, resting-state networks, Granger causality