Variability of Single Pulse Electrical Stimulation Responses Recorded with Intracranial Electroencephalography in Epileptic Patients

Cohort studies of brain stimulations performed with stereo-electroencephalographic (SEEG) electrodes in epileptic patients allow to derive large scale functional connectivity. It is known, however, that brain responses to electrical or magnetic stimulation techniques are not always reproducible. Here, we study variability of responses to single pulse SEEG electrical stimulation. We introduce a second-order probability analysis, i.e. we extend estimation of connection probabilities, defined as the proportion of responses trespassing a statistical threshold (determined in terms of Z-score with respect to spontaneous neuronal activity before stimulation) over all responses and derived from a number of individual measurements, to an analysis of pairs of measurements. Data from 445 patients were processed. We found that variability between two equivalent measurements is substantial in particular conditions. For long ( > ~ 90 mm) distances between stimulating and recording sites, and threshold value Z = 3, correlation between measurements drops almost to zero. In general, it remains below 0.5 when the threshold is smaller than Z = 4 or the stimulating current intensity is 1 mA. It grows with an increase of either of these factors. Variability is independent of interictal spiking rates in the stimulating and recording sites. We conclude that responses to SEEG stimulation in the human brain are variable, i.e. in a subject at rest, two stimulation trains performed at the same electrode contacts and with the same protocol can give discrepant results. Our findings highlight an advantage of probabilistic interpretation of such results even in the context of a single individual.