• Josephine Heine, Harald Prüss, Ute A Kopp, Florian Wegner, Florian Then Bergh, Thomas Münte, Klaus-Peter Wandinger, Friedemann Paul, Thorsten Bartsch, and Carsten Finke.
• Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
• J. Neurol. Neurosurg. Psychiatr. 2018 Nov 1; 89 (11): 1191-1199.

ObjectiveHippocampal inflammation in anti-LGI1 encephalitis causes memory deficits, seizures and behavioural abnormalities. Recent findings suggest that extralimbic brain areas are additionally affected and that patients also suffer from non-limbic cognitive symptoms. Moreover, up to 60% of patients show no structural MRI abnormalities in the acute disease stage. We therefore investigated whether functional connectivity analyses can identify brain network changes underlying disease-related symptoms.MethodsWe studied 27 patients and a matched healthy control group using structural and functional MRI. Intrinsic functional networks were analysed using Independent Component Analysis and Dual Regression. Cognitive testing covered working memory, episodic memory, attention and executive function.ResultsOur analysis revealed functional connectivity alterations in several large-scale networks, including the default mode network (DMN) which showed an aberrant structure-function relationship with the damaged hippocampus. In addition, connectivity in the sensorimotor, salience and higher visual networks was impaired independent of hippocampal damage. Increased connectivity in ventral and dorsal DMN regions significantly correlated with better memory performance. In contrast, stronger connectivity of the insula with the salience network and DMN was linked to impaired memory function.ConclusionsAnti-LGI1 encephalitis is associated with a characteristic pattern of widespread functional network alterations. Increased DMN connectivity seems to represent a compensatory mechanism for memory impairment induced by hippocampal damage. Network analyses may provide a key to the understanding of clinical symptoms in autoimmune encephalitis and reveal changes of brain function beyond apparent structural damage.© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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