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Seizure. 2017 Jan;44:27-36. doi: 10.1016/j.seizure.2016.11.003. Epub 2016 Nov 14.

Single pulse electrical stimulation to probe functional and pathological connectivity in epilepsy.

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Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan. Electronic address:
Department of Neurosurgery, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
Epilepsy Center, Cleveland Clinic Foundation, Cleveland, USA.


In the last decade, single pulse electrical stimulation (SPES) has been used as an investigational tool in the field of epilepsy surgery. Direct cortical stimulation applied at a frequency of ∼1Hz can probe cortico-cortical connections by averaging electrocorticogram time-lock to the stimuli (2×20-30 trials). These evoked potentials that emanate from adjacent and remote cortices have been termed cortico-cortical evoked potentials (CCEPs). Although limited to patients undergoing invasive presurgical evaluations with intracranial electrodes, CCEP provides a novel way to explore inter-areal connectivity in vivo in the living human brain to probe functional brain networks such as language and cognitive motor networks. In addition to its impact on systems neuroscience, this method, in combination with 50Hz electrical cortical stimulation, could contribute clinically to map the functional brain systems by tracking the cortico-cortical connections among the functional cortical regions in each individual patient. This approach may help identify the normal cortico-cortical network within pathology as well as reveal connections that might arise from neural plasticity. Because of its high practicality, it has been recently applied for intraoperative monitoring of the functional brain networks for patients with brain tumor. With regard to epilepsy, SPES has been used for the two major purposes, one to probe cortical excitability of the focus, namely, epileptogenicity, and the other to probe seizure networks. Both early (i.e., CCEP) and delayed responses, and probably their high frequency oscillation counterparts, are regarded as a surrogate marker of epileptogenicity. With regards to its impact on the human brain connectivity map, worldwide collaboration is warranted to establish the standardized CCEP connectivity map as a solid reference for non-invasive connectome researches.


Cortico-cortical evoked potential; Effective connectivity; Electrical cortical stimulation; Electrocorticogram; Functional system mapping; Single pulse electrical stimulation

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