Beyond the limbic system

disruption and functional compensation of large-scale brain networks in patients with anti-LGI1 encephalitis

  • Heine, Josephine
  • Prüss, Harald
  • Kopp, Ute A
  • Wegner, Florian
  • Then Bergh, Florian
  • Münte, Thomas
  • Wandinger, Klaus-Peter
  • Paul, Friedemann
  • Bartsch, Thorsten
  • Finke, Carsten

  • 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 German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany

    3 Department of Neurology, Hannover Medical School, Hannover, Germany

    4 Department of Neurology, University of Leipzig, Leipzig, Germany

    5 Department of Neurology, University Hospital Schleswig-Holstein, Lübeck, Germany

    6 Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Lübeck, Germany

    7 Neurocure Clinical Research Center and Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité – Universitätsmedizin Berlin, Berlin, Germany

    8 Berlin Center for Advanced Neuroimaging, Charité – Universitätsmedizin Berlin, Berlin, Germany

    9 Department of Neurology, Memory Disorders and Plasticity Group, University Hospital Schleswig-Holstein, Berlin, Germany

    10 Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany

Professor Friedemann Paul, NeuroCure Clinical Research Center, Charité – Universitätsmedizin Berlin, Berlin 10117, Germany; [email protected]

Received December 07, 2017

Received in revised form April 24, 2018

Accepted May 09, 2018

Journal of Neurology, Neurosurgery, & Psychiatry 89(11):p 1191-1199, November 2018. | DOI: 10.1136/jnnp-2017-317780

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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