Abstract
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.
Highlights
Anti-N-methyl-D-aspartate receptor encephalitis (NMDAR) is an autoimmune disease mediated by IgG antibodies to the NR1 subunits of NMDA receptors
No significant differences was found for age, gender, years of education, and head motion between anti-NMDAR encephalitis patients and healthy controls (HC) (p > 0.05)
We found that the superior parietal lobe (Parietal_sup_L) exhibited enhanced causal connectivity to the left insula compared to controls (Table 3 and Figure 1)
Summary
Anti-N-methyl-D-aspartate receptor encephalitis (NMDAR) is an autoimmune disease mediated by IgG antibodies to the NR1 subunits of NMDA receptors. GCA is a reliable method for assessing causal association which can study directional connections between different brain regions and dynamically observe changes in brain networks. It has been used in several studies examining the pathogenesis of neurodegenerative diseases (Li et al, 2019; Pang et al, 2019; Hao et al, 2020). We used graph theory to quantify the topological properties of the brain network in anti-NMDAR encephalitis patients to elucidate the network nodes and causal connectivity of brain function. 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
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