Objective Hippocampal 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.
Methods We 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.
Results Our 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.
Conclusions Anti-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.
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Contributors Study concept and design: JH, FP, TB, CF. Acquisition, analysis or interpretation of the data: JH, HP, UAK, FW, FTB, TM, K-PW, FP, TB, CF. Drafting of the manuscript: JH, CF. Critical revision of the manuscript for intellectual content: JH, HP, UAK, FW, FTB, TM, K-PW, FP, TB, CF. Statistical analysis: JH, CF. Administrative, technical or material support: HP, UAK, FW, TM, K-PW, FP, TB, CF. Study supervision: HP, FP, TB, CF.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. FP is supported by Deutsche Forschungsgemeinschaft (DFG Exc 257).
Competing interests FP and TB report personal fees outside the submitted work. None declared for all other authors.
Patient consent Not required.
Ethics approval Ethics committees at the Charité University Hospital Berlin and the University Hospital of Kiel.
Provenance and peer review Not commissioned; externally peer reviewed.