Aberrant Multimodal Brain Networks in Patients with Anti-NMDA Receptor Encephalitis

Abstract

Objective: To explore large-scale brain network alterations and examine their clinical and neuropsychological relevance in patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Methods: We enrolled 24 patients with anti-NMDAR encephalitis and 26 matched healthy controls (HCs) who underwent a comprehensive neuropsychological test battery and multimodal MRI scanning. Based on the multimodal MRI dataset, individual morphological, structural and functional brain networks were constructed and compared between the two groups at multiple levels. The associations with clinical/neuropsychological variables and the discriminant ability of significant alterations were further studied. Results: Compared with the HCs, patients with anti-NMDAR encephalitis exhibited cognitive deficits in verbal memory, spatial episodic memory and information processing speed. Multimodal network analysis revealed complicated network disruption patterns in the patients depending on the imaging modalities. Specifically, anti-NMDAR encephalitis profoundly affected morphological and structural networks, but subtle alterations were observed in functional networks. Intriguingly, decreased hierarchy and increased nodal centrality in the lateral orbital gyrus were convergently observed among the three types of networks in the patients. Moreover, the alterations, particularly those from structural networks, correlated well with clinical and neuropsychological variables of the patients and could distinguish the diseased individuals from the HCs with excellent performance (area under the curve = 0.933). Conclusions: The current study provides a comprehensive view of characteristic multimodal network dysfunction in anti-NMDAR encephalitis, which is crucial to establish new diagnostic biomarkers and promising therapeutic targets for the disease. Funding Statement: This work was supported by the National Natural Science Foundation of China (grant number 81922036, 81671764, 81571631, and 81401377), the ECTRIMS-MAGNIMS Fellowship from The European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (YL) and the Beijing Natural Science fund (grant number 7162077). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study was approved by the institutional review board of Xuanwu hospital, Capital Medical University, Beijing, China and written informed consent was obtained from each participant.