Cellular Substrates of Functional Network Integration and Memory in Temporal Lobe Epilepsy

Linda Douw*, Ida A. Nissen, Sophie M.D.D. Fitzsimmons, Fernando A.N. Santos, Arjan Hillebrand, Elisabeth C.W. Van Straaten, Cornelis J. Stam, Philip C. De Witt Hamer, Johannes C. Baayen, Martin Klein, Jaap C. Reijneveld, Djai B. Heyer, Matthijs B. Verhoog, René Wilbers, Sarah Hunt, Huibert D. Mansvelder, Jeroen J.G. Geurts, Christiaan P.J. De Kock, Natalia A. Goriounova

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


Temporal lobe epilepsy (TLE) patients are at risk of memory deficits, which have been linked to functional network disturbances, particularly of integration of the default mode network (DMN). However, the cellular substrates of functional network integration are unknown. We leverage a unique cross-scale dataset of drug-resistant TLE patients (n = 31), who underwent pseudo resting-state functional magnetic resonance imaging (fMRI), resting-state magnetoencephalography (MEG) and/or neuropsychological testing before neurosurgery. fMRI and MEG underwent atlas-based connectivity analyses. Functional network centrality of the lateral middle temporal gyrus, part of the DMN, was used as a measure of local network integration. Subsequently, non-pathological cortical tissue from this region was used for single cell morphological and electrophysiological patch-clamp analysis, assessing integration in terms of total dendritic length and action potential rise speed. As could be hypothesized, greater network centrality related to better memory performance. Moreover, greater network centrality correlated with more integrative properties at the cellular level across patients. We conclude that individual differences in cognitively relevant functional network integration of a DMN region are mirrored by differences in cellular integrative properties of this region in TLE patients. These findings connect previously separate scales of investigation, increasing translational insight into focal pathology and large-scale network disturbances in TLE.

Original languageEnglish
Pages (from-to)2424-2436
Number of pages13
JournalCerebral cortex (New York, N.Y. : 1991)
Issue number11
Early online date25 Sept 2021
Publication statusPublished - 1 Jun 2022

Bibliographical note

Funding Information:
Nederlands Epilepsie Fonds (NEF 08-08, 09-09 for L.D. and J.C.R.); the Dutch Organization for Scientific Research (NWO Veni 016.146.086 and NWO Vidi 198.015 for L.D.); Society in Science (Branco Weiss Fellowship for L.D.); L.D., N.A.G. and C.P.J.d.K. received funding from Amsterdam Neuroscience for this work. Dutch Organization for Scientific Research (NWO Veni, 016.Veni.171.017 to N.A.G.); Amsterdam Neuroscience (N.A.G.); the Nederlands Epilepsie Fonds (NEF 14-16 to I.A.N.and A.H.); the Netherlands Organisation for Health Research and Development (ZonMW grant 95105006); European Union's Horizon 2020 Framework Programme for Research and Innovation (grant 785907 for Human Brain Project SGA2 and SGA3 to H.D.M.).

Publisher Copyright:
© 2021 The Author(s) 2021. Published by Oxford University Press. All rights reserved.


  • action potential kinetics
  • cellular morphology
  • connectome
  • graph theory
  • resting-state fMRI


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