Article Text

Download PDFPDF
Research paper
Beyond the limbic system: disruption and functional compensation of large-scale brain networks in patients with anti-LGI1 encephalitis
  1. Josephine Heine1,
  2. Harald Prüss1,2,
  3. Ute A Kopp1,
  4. Florian Wegner3,
  5. Florian Then Bergh4,
  6. Thomas Münte5,
  7. Klaus-Peter Wandinger5,6,
  8. Friedemann Paul1,7,8,
  9. Thorsten Bartsch9,
  10. Carsten Finke1,8,10
  1. 1 Department of Neurology, Charité – Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
  2. 2 German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany
  3. 3 Department of Neurology, Hannover Medical School, Hannover, Germany
  4. 4 Department of Neurology, University of Leipzig, Leipzig, Germany
  5. 5 Department of Neurology, University Hospital Schleswig-Holstein, Lübeck, Germany
  6. 6 Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Lübeck, Germany
  7. 7 Neurocure Clinical Research Center and Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité – Universitätsmedizin Berlin, Berlin, Germany
  8. 8 Berlin Center for Advanced Neuroimaging, Charité – Universitätsmedizin Berlin, Berlin, Germany
  9. 9 Department of Neurology, Memory Disorders and Plasticity Group, University Hospital Schleswig-Holstein, Berlin, Germany
  10. 10 Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany
  1. Correspondence to Professor Friedemann Paul, NeuroCure Clinical Research Center, Charité – Universitätsmedizin Berlin, Berlin 10117, Germany; friedemann.paul{at}


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.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • 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.