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BackgroundIn recent years, imaging technologies have been rapidly evolving, with an emphasis on the characterization of brain structure changes and functional imaging in patients with autoimmune encephalitis. However, the neural basis of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and its linked cognitive decline is unclear. Our research aimed to assess changes in the functional brain network in patients with anti-NMDAR encephalitis and whether these changes lead to cognitive impairment.MethodsTwenty-one anti-NMDAR encephalitis patients and 22 age-, gender-, and education status-matched healthy controls were assessed using resting functional magnetic resonance imaging (fMRI) scanning and neuropsychological tests, including the Hamilton Depression Scale (HAMD24), the Montreal Cognitive Assessment (MoCA), and the Hamilton Anxiety Scale (HAMA). A functional brain network was constructed using fMRI, and the topology of the network parameters was analyzed using graph theory. Next, we extracted the aberrant topological parameters of the functional network as seeds and compared causal connectivity with the whole brain. Lastly, we explored the correlation of aberrant topological structures with deficits in cognitive performance.ResultsRelative to healthy controls, anti-NMDAR encephalitis patients exhibited decreased MoCA scores and increased HAMA and HAMD24 scores (p < 0.05). The nodal clustering coefficient and nodal local efficiency of the left insula (Insula_L) were significantly decreased in anti-NMDAR encephalitis patients (p < 0.05 following Bonferroni correction). Moreover, anti-NMDAR encephalitis patients showed a weakened causal connectivity from the left insula to the left inferior parietal lobe (Parietal_Inf_L) compared to healthy controls. Conversely, the left superior parietal lobe (Parietal_sup_L) exhibited an enhanced causal connectivity to the left insula in anti-NMDAR encephalitis patients compared to controls. Unexpectedly, these alterations were not correlated with any neuropsychological test scores.ConclusionThis research describes topological abnormalities in the functional brain network in anti-NMDAR encephalitis. These results will be conducive to understand the structure and function of the brain network of patients with anti-NMDAR encephalitis and further explore the neuropathophysiological mechanisms.

Background:Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disease with typical clinical features. Whether and how cerebral gray matter structural damage inherent to the disorder affects cognitive function in patients is still unclear. Therefore, this study aimed to explore the changes in cerebral gray matter volume and whether these alterations contribute to cognitive impairment and mood disorders.MethodsForty patients with anti-NMDAR encephalitis and forty healthy controls (HCs) matched for gender, age, and education were recruited. All participants underwent attention network tests (ANT), neuropsychological tests and magnetic resonance imaging (MRI). Voxel-based morphological analysis (VBM) and correlation analysis was performed on all participants. Finally, according to the course of disease, patients were divided into two groups: NMDARE_SD (short duration; course ≤ 2 years since diagnosis) and NMDARE_LD (long duration; course >2 years since diagnosis), to evaluate gray matter volume changes that differ as a function of disease course.ResultsCompared to HCs, patients with anti-NMDAR encephalitis showed decreased executive control ability and lower MoCA score, while increased anxiety and depression as reflected by HAMA and HAMD24 scores (all P < 0.05). In VBM analysis, patients showed decreased gray matter volume in bilateral thalamus, left medial prefrontal cortex (mPFC_L), left superior temporal gyrus (STG_L), and left rectus gyrus. In the analysis stratified by disease course, the NMDARE_LD group exhibited decreased gray matter volume in the left precuneus and right posterior cerebellar lobe compared to the NMDARE_SD group.ConclusionsPatients with anti-NMDAR encephalitis have cognitive, executive, and emotional dysfunction, and the sites of gray matter atrophy are concentrated in the thalamus, frontal lobe, and temporal lobe. These abnormalities may be involved in the process of cognitive and affective dysfunction.Patients with different courses of anti-NMDAR encephalitis have different brain atrophy sites. These results may help to clarify the contradiction between clinical and imaging manifestations of anti NMDAR encephalitis, which is worthy of further longitudinal studies.