Cerebral Functional Activity And Connectivity Changes In Anti-N-Methyl-D-Aspartate Receptor Encephalitis:A Resting-State FMRI Study

Objective Anti-N-methyl-D-aspartate（NMDA）receptor encephalitis showing severe neuropsychiatric symptoms and cognitive dysfunction is the most common type of autoimmune encephalitis.However,the corresponding standard clinical magnetic resonance imaging（MRI）presents normal or atypical in the majority of patients with anti-NMDA receptor encephalitis.Even if some lesions can be observed,it is difficult to explain all the clinical manifestations,which leads to the clinical-radiological contradiction.Here,this study aimed to investigate the cerebral spontaneous activity and connectivity changes by using resting-state functional MRI technology in patients with anti-NMDA receptor encephalitis,and whether these alterations contributed to cognition and mood disorders.Methods A total of 17 patients with anti-NMDA receptor encephalitis diagnosed by the First Affiliated Hospital of Guangxi Medical University from January2015 to June 2018 were divided into patient group,and eighteen gender,age and education-matched healthy controls（HC group）were recruited.All participants underwent neuropsychological tests(including Montreal Cognitive Assessment（Mo CA）,Hamilton Anxiety Scale（HAMA）,and Hamilton Depression Scale(HAMD₂₄))and resting-state functional MRI.MRI data was firstly analyzed by amplitude of low-frequency fluctuation（ALFF）,and two-sample t test was used to analyze the difference between patient group and HC group.Then,brain regions with altered ALFF between groups were selected as regions of interest for the further functional connectivity（FC）analysis.Correlation analyses were used between the ALFF and FC values in brain regions which were significantly different from the other brain regions and neuropsychological performance.Results Relative to the healthy controls,patients with anti-NMDA receptor encephalitis performed inferiorly in the total Mo CA score and its subitems included orientation,calculate,delayed recall,visual perception and naming scores,and showed anxiety and depression disorders with higher HAMA and HAMD₂₄ scores（all P<0.05）.In the brain functional activity analysis,the patients showed decreased ALFF values in the bilateral posterior cingulate gyrus,left precuneus,and bilateral cerebellum（false-discovery-rate corrected,P<0.05）.Furthermore,relative to the control group,the patients showed significantly increased FC between the left posterior cingulate cortex（PCC）and the bilateral lingual gyrus,right calcarine,right cuneus,also between the right PCC and the right fusiform gyrus,bilateral lingual gyrus,left calcarine,left cuneus,and right posterior central gyrus（false-discovery-rate corrected,P<0.05）.FC strength between the left posterior cingulate gyrus and right cuneus,and between the right posterior cingulate gyrus and left cuneus were both positively correlated with delayed recall of Mo CA scores（r=0.485,P=0.048;r=0.550,P=0.022）.Conclusion Patients with anti-NMDA receptor encephalitis exist cognitive and emotion deficits.The present study highlight that decreased spontaneous neural activities and abnormal FC exhibited in the patients with anti-NMDA receptor encephalitis,which may participate in the process of cognition and emotion deficits.These results may help to elucidate the clinical radiological contradictions in anti-NMDA receptor encephalitis and contribute to deeper understanding of the pathophysiological mechanism of the disease.