Local and distant responses to single pulse electrical stimulation reflect different forms of connectivity

Britni Crocker, Lauren Ostrowski, Ziv M. Williams, Darin D. Dougherty, Emad N. Eskandar, Alik S. Widge, Catherine J. Chu, Sydney S. Cash, Angelique C. Paulk

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Measuring connectivity in the human brain involves innumerable approaches using both noninvasive (fMRI, EEG) and invasive (intracranial EEG or iEEG) recording modalities, including the use of external probing stimuli, such as direct electrical stimulation. To examine how different measures of connectivity correlate with one another, we compared ‘passive’ measures of connectivity during resting state conditions to the more ‘active’ probing measures of connectivity with single pulse electrical stimulation (SPES). We measured the network engagement and spread of the cortico-cortico evoked potential (CCEP) induced by SPES at 53 out of 104 total sites across the brain, including cortical and subcortical regions, in patients with intractable epilepsy (N=11) who were undergoing intracranial recordings as a part of their clinical care for identifying seizure onset zones. We compared the CCEP network to functional, effective, and structural measures of connectivity during a resting state in each patient. Functional and effective connectivity measures included correlation or Granger causality measures applied to stereoEEG (sEEGs) recordings. Structural connectivity was derived from diffusion tensor imaging (DTI) acquired before intracranial electrode implant and monitoring (N=8). The CCEP network was most similar to the resting state voltage correlation network in channels near to the stimulation location. In contrast, the distant CCEP network was most similar to the DTI network. Other connectivity measures were not as similar to the CCEP network. These results demonstrate that different connectivity measures, including those derived from active stimulation-based probing, measure different, complementary aspects of regional interrelationships in the brain.

Original languageEnglish (US)
Article number118094
StatePublished - Aug 15 2021

Bibliographical note

Funding Information:
We would like to especially thank the patients who participated for their time and help. We thank Erica Johnson, Gavin Belok, Kara Farnes, Jessica Chang, Daniel Soper, and Mia Borzello for technical assistance, particularly in the MRI reconstruction and registration, and Enterprise Research Infrastructure & Services at Partners Healthcare for their in-depth support and for the provision of the ERISOne Linux Computing Cluster. This work was supported by NINDS-K24 [K24-NS088568-01A1]; the Tiny Blue Dot Foundation; and the United States Department of Energy Computational Sciences Graduate Fellowship [DE-FG02-97ER25308] to BC. This research was sponsored by the U.S. Army Research Office and Defense Advanced Research Projects Agency (DARPA) under Cooperative Agreement Number W911NF-14-2-0045 issued by ARO contracting office in support of DARPA's SUBNETS Program. The views, opinions, and/or findings expressed are those of the authors and should not be interpreted as representing the official views or policies of the Department of Defense or the U.S. Government.

Publisher Copyright:
© 2021


  • Connectivity
  • Diffusion tensor imaging
  • Direct electrical stimulation
  • Intracranial
  • sEEG


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