Investigation of the effective connectivity between the anti-NMDAR encephalitis default mode network and the medial temporal lobe network using spectral dynamic causal modelling.

Abstract

Background: Research has indicated that anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis involves global network dysfunction, linking memory deficits to connectivity in the hippocampus, default mode network (DMN), and medial temporal lobe network (MTL). Most relevant cognitive studies have focused on functional connectivity (FC) rather than effective connectivity (EC), meaning that the directed interactions and causal relationships between the DMN and MTL remain unexplored.

Methods: Herein, we collected resting-state functional MRI (fMRI) data from 23 patients with anti-NMDAR encephalitis (mean age 30.04 ± 12.67 years) and 23 matched controls (mean age 28.87 ± 9.36 years). Spectral dynamic causal modelling (spDCM) was applied to assess the effective connectivity among the 12 predefined regions of interest in the DMN and MTL.

Results: Effective connectivity (EC) within and between the DMN and MTL networks significantly differed in the NMDAR-resistant encephalitis group compared to controls; the positive EC within the DMN and from the MTL to the DMN was enhanced, while the negative EC from the DMN to the MTL increased, and the positive EC within the MTL decreased. The mean DMN connectivity values in the anti-NMDAR group were negatively correlated with California Verbal Learning Test (CVLT) and Modified Mental State Examination (MMSE) scores, an effect which remained significant after adjusting for age, sex, and body mass index.

Conclusion: This study identified differences in the connectivity between the DMN and MTL networks in patients with post-acute anti-NMDAR encephalitis, suggesting a possible disconnection. The parahippocampal gyrus (PHG) mediates connections between the hippocampus and the posterior cingulate cortex (PCC). Structural or functional loss of the PHG may affect the integration between the MTL memory system and DMN nodes, correlating with cognitive deficits. This study provides crucial results to improve our understanding of the directed integration between the DMN and MTL networks, providing new evidence.