A comparative study of the effects of pulse parameters for intracranial direct electrical stimulation in epilepsy Cristian Donos a , Ioana Mîndrut ßa ˘ b,c , Jean Ciurea d , Mihai Dragos Ma ˘lîia c , Andrei Barborica a,e,⇑ a Physics Department, University of Bucharest, Bucharest, Romania b Neurology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania c Neurology Department, University Emergency Hospital, Bucharest, Romania d Neurosurgery Department, Bagdasar-Arseni Hospital, Bucharest, Romania e FHC Inc., Bowdoin, ME, USA article info Article history: Accepted 13 February 2015 Available online xxxx Keywords: Single-pulse electrical stimulation Drug-resistant epilepsy Stereoelectroencephalography highlights  The effects of variable pulse duration, intensity, phase, and polarity were studied.  A key feature is the multi-parametric stimulation on the same stereo-EEG contacts.  The common factor driving the magnitude of the EEG responses is the applied charge/phase. abstract Objectives: Intracranial direct electrical stimulation (iDES) uses different parameters for mapping the epi- leptogenic and functional areas in patients with drug-resistant epilepsy. We aim at finding the common factor driving the electrographic responses to various iDES protocols reported in the literature. Methods: We recorded early responses to single-pulse iDES in 11 subjects undergoing stereoelectroen- cephalographic presurgical evaluation. We systematically explored the role of several pulse parameters in evoking responses: monophasic versus biphasic pulses, current intensity, and pulse duration. We per- formed a correlation and regression analysis between responses to different protocols by amplitude, duration, and charge per phase. Results: Regression analysis revealed that the responses were similar for the same charge per phase, regardless of their pulse duration and amplitude. Over eighty percent (82.8%) of the responses to variable pulse duration biphasic stimulation and between 58.6% and 81.9% of the responses to monophasic stim- ulation, depending on pulse polarity, were correlated to the responses evoked by the variable amplitude biphasic protocol, when expressing stimulus strength in terms of charge per phase. Conclusions: Regardless of the combination of different stimulation currents, it is the underlying charge per phase parameter that determines the magnitude of the responses to single-pulse electrical stim- ulation. Significance: Our results provide a unifying method for comparing iDES protocols. Ó 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. 1. Introduction Patients with drug-resistant epilepsy undergoing presurgical evaluation are often investigated using intracranial direct electrical stimulation (iDES), in addition to recording the spontaneous electroencephalographic (EEG) activity. Cortical regions and/or axonal tracts are directly stimulated using subdural grids or depth electrodes, in order to evoke responses that help in delineating the epileptogenic network and eloquent cortex. Different protocols are used in practice to either evoke after-discharges or obtain clinical responses. However, for the purpose of this study, we focus only on subclinical stimulation protocols and analyze the EEG responses for different pulse parameters. This approach allows us to objec- tively evaluate the efficacy of the stimulation by performing a http://dx.doi.org/10.1016/j.clinph.2015.02.013 1388-2457/Ó 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. ⇑ Corresponding author at: Physics Department, Bucharest University, Electricity, Solid State and Biophysics Section, P.O. Box MG – 11, Bucuresti-Magurele RO 077125, Romania. Tel.: +40 21 457 4949; fax: +4 021 457 4521. E-mail address: andrei.barborica@fizica.unibuc.ro (A. Barborica). Clinical Neurophysiology xxx (2015) xxx–xxx Contents lists available at ScienceDirect Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph Please cite this article in press as: Donos C et al. A comparative study of the effects of pulse parameters for intracranial direct electrical stimulation in epilepsy. Clin Neurophysiol (2015), http://dx.doi.org/10.1016/j.clinph.2015.02.013