Mapping Epileptic Networks Using Simultaneous Intracranial EEG-fMRI

Umair J. Chaudhary, Maria Centeno, David W. Carmichael, Beate Diehl, Matthew C. Walker, John S. Duncan, Louis Lemieux*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background: Potentially curative epilepsy surgery can be offered if a single, discrete epileptogenic zone (EZ) can be identified. For individuals in whom there is no clear concordance between clinical localization, scalp EEG, and imaging data, intracranial EEG (icEEG) may be needed to confirm a predefined hypothesis regarding irritative zone (IZ), seizure onset zone (SOZ), and EZ prior to surgery. However, icEEG has limited spatial sampling and may fail to reveal the full extent of epileptogenic network if predefined hypothesis is not correct. Simultaneous icEEG-fMRI has been safely acquired in humans and allows exploration of neuronal activity at the whole-brain level related to interictal epileptiform discharges (IED) captured intracranially. Methods: We report icEEG-fMRI in eight patients with refractory focal epilepsy who had resective surgery and good postsurgical outcome. Surgical resection volume in seizure-free patients post-surgically reflects confirmed identification of the EZ. IEDs on icEEG were classified according to their topographic distribution and localization (Focal, Regional, Widespread, and Non-contiguous). We also divided IEDs by their location within the surgical resection volume [primary IZ (IZ1) IED] or outside [secondary IZ (IZ2) IED]. The distribution of fMRI blood oxygen level-dependent (BOLD) changes associated with individual IED classes were assessed over the whole brain using a general linear model. The concordance of resulting BOLD map was evaluated by comparing localization of BOLD clusters with surgical resection volume. Additionally, we compared the concordance of BOLD maps and presence of BOLD clusters in remote brain areas: precuneus, cuneus, cingulate, medial frontal, and thalamus for different IED classes. Results: A total of 38 different topographic IED classes were identified across the 8 patients: Focal (22) and non-focal (16, Regional = 9, Widespread = 2, Non-contiguous = 5). Twenty-nine IEDs originated from IZ1 and 9 from IZ2. All IED classes were associated with BOLD changes. BOLD maps were concordant with the surgical resection volume for 27/38 (71%) IED classes, showing statistical global maximum BOLD cluster or another cluster in the surgical resection volume. The concordance of BOLD maps with surgical resection volume was greater (p < 0.05) for non-focal (87.5%, 14/16) as compared to Focal (59%, 13/22) IED classes. Additionally, BOLD clusters in remote cortical and deep brain areas were present in 84% (32/38) of BOLD maps, more commonly (15/16; 93%) for non-focal IED-related BOLD maps. Conclusions: Simultaneous icEEG-fMRI can reveal BOLD changes at the whole-brain level for a wide range of IEDs on icEEG. BOLD clusters within surgical resection volume and remote brain areas were more commonly seen for non-focal IED classes, suggesting that a wider hemodynamic network is at play.

Original languageEnglish
Article number693504
JournalFrontiers in Neurology
Publication statusPublished - 21 Sep 2021
Externally publishedYes

Bibliographical note

Funding Information:
We are thankful to Dr. Tim Wehner (Neurophysiologist and Epileptologist), Catherine Scott (Electrophysiologist), and the Department of Clinical Neurophysiology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK for their expert help for obtaining intracranial EEG. We thank Prof. Maria Thom at the Department of Neuropathology, Institute of Neurology, Queen Square for her expert help with the interpretation of neuropathological diagnoses. We are grateful to the radiographers Lisa Strycharczuk, Bruce Metheringham, and Alison Duncan, and the MR physicists Mark White and Laura Mancini of the Lysholm Department of Neuroradiology and Neurophysics at the National Hospital for Neurology and Neurosurgery (UCLH NHS Foundation Trust), for their expert scanning assistance.

Funding Information:
This work was partly funded through grants and bursaries from the Medical Research Council (MRC Grant No. G0301067), Action Medical Research, Swiss National Science Foundation (SNF grant 320030-141165 and 33CM30-140332, SPUM Epilepsy), University of Modena, Reggio Emilia, and UCL Institute of Neurology. This work was undertaken at UCLH/UCL, which received a proportion of funding from the Department of Health’s NIHR Biomedical Research Centers funding scheme.

Publisher Copyright:
© Copyright © 2021 Chaudhary, Centeno, Carmichael, Diehl, Walker, Duncan and Lemieux.


  • BOLD
  • EEG-fMRI
  • IED/spikes
  • intracranial EEG
  • post-surgical outcome


Dive into the research topics of 'Mapping Epileptic Networks Using Simultaneous Intracranial EEG-fMRI'. Together they form a unique fingerprint.

Cite this