Effects of stimulation intensity on intracranial cortico-cortical evoked potentials: A titration study

Mark A. Hays, Rachel J. Smith, Babitha Haridas, Christopher Coogan, Nathan E. Crone, Joon Y. Kang

Research output: Contribution to journalArticlepeer-review


Objective: The aim of the present study was to investigate the optimal stimulation parameters for eliciting cortico-cortical evoked potentials (CCEPs) for mapping functional and epileptogenic networks. Methods: We studied 13 patients with refractory epilepsy undergoing intracranial EEG monitoring. We systematically titrated the intensity of single-pulse electrical stimulation at multiple sites to assess the effect of increasing current on salient features of CCEPs such as N1 potential magnitude, signal to noise ratio, waveform similarity, and spatial distribution of responses. Responses at each incremental stimulation setting were compared to each other and to a final set of responses at the maximum intensity used in each patient (3.5–10 mA, median 6 mA). Results: We found that with a biphasic 0.15 ms/phase pulse at least 2–4 mA is needed to differentiate between non-responsive and responsive sites, and that stimulation currents of 6–7 mA are needed to maximize amplitude and spatial distribution of N1 responses and stabilize waveform morphology. Conclusions: We determined a minimum stimulation threshold necessary for eliciting CCEPs, as well as a point at which the current-dependent relationship of several response metrics all saturate. Significance: This titration study provides practical, immediate guidance on optimal stimulation parameters to study specific features of CCEPs, which have been increasingly used to map both functional and epileptic brain networks in humans.

Original languageEnglish (US)
Pages (from-to)2766-2777
Number of pages12
JournalClinical Neurophysiology
Issue number11
StatePublished - Nov 2021


  • Cortico-cortical evoked potential
  • Effective connectivity
  • Intracranial EEG
  • Single-pulse electrical stimulation

ASJC Scopus subject areas

  • Sensory Systems
  • Neurology
  • Clinical Neurology
  • Physiology (medical)


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