Disconnection of the hippocampus and amygdala associated with lesion load in relapsing–remitting multiple sclerosis: a structural and functional connectivity study

Abstract

Fuqing Zhou,1,2,* Ying Zhuang,3,* Lingling Wang,4 Yue Zhang,5 Lin Wu,1,2 Xianjun Zeng,1,2 Honghan Gong1,2 1Department of Radiology, The First Affiliated Hospital, Nanchang University, 2Jiangxi Province Medical Imaging Research Institute, 3Department of Oncology, The Second Hospital of Nanchang, Nanchang, Jiangxi Province, 4Department of Geriatrics, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, 5Department of Radiology, The Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi Province, People’s Republic of China *These authors contributed equally to this work Background and purpose: Little is known about the functional and structural connectivity (FC and SC) of the hippocampus and amygdala, which are two important structures involved in cognitive processes, or their involvement in relapsing–remitting multiple sclerosis (RRMS). In this study, we aimed to examine the connectivity of white-matter (WM) tracts and the synchrony of intrinsic neuronal activity in outer regions connected with the hippocampus or amygdala in RRMS patients.Patients and methods: Twenty-three RRMS patients and 23 healthy subjects participated in this study. Diffusion tensor probabilistic tractography was used to examine the SC, the FC correlation coefficient (FC-CC) and combined FC strength (FCS), which was derived from the resting-state functional magnetic resonance imaging used to examine the FC, of the connection between the hippocampus or the amygdala and other regions, and the correlations of these connections with clinical markers. Results: Compared with healthy subjects, the RRMS patients showed significantly decreased SC and increased FCS of the bilateral hippocampus, and left amygdala. Their slightly increased FC-CC was positively correlated with WM tract damage in the right hippocampus (ρ=0.57, P=0.005); an increased FCS was also positively correlated with WM tract damage in the right amygdala. A relationship was observed between the WM lesion load and SC alterations, including the lg(N tracts) of the right hippocampus (ρ=-0.68, P<0.05), lg(N tracts) (ρ=-0.69, P<0.05), and fractional anisotropy (ρ=-0.68, P<0.05) and radial diffusivity of the left hippocampus (ρ=0.45, P<0.05). A relationship between WM lesion load and FCS of the left amygdale was also observed. Conclusion: The concurrent increased functional connections and demyelination-related structural disconnectivity between the hippocampus or amygdala and other regions in RRMS suggest that the functional–structural relationships require further investigation. Keywords: relapsing–remitting multiple sclerosis, hippocampus, limbic system, functional connectivity, structural connectivity, fiber tractography