Late responses missed by expert N1 maps occur near SEEG stimulation sites

In 8 patients with stereo-EEG (SEEG), we tested whether single-pulse stimulation evoked late responses (100–300 ms; N2) at contacts experts had marked as having no early N1 response (10–50 ms). The analysis used 78 stimulated pairs, 8 pulses per pair (4 per polarity; 1 or 2 mA), and exact sign-flip tests (256 patterns; detection threshold p ≤ 0.01), compared with a no-pulse sham window. With a common median reference, N2 detections at expert N1-negative contacts exceeded sham detections (10.4% vs 1.1%; mean patient-level difference 0.093; exact one-sided sign-flip p = 0.0039), but the apparent excess also extended to contacts ≥50 mm from stimulation. With a local bipolar reference added after inspection (post hoc), rates were 5.8% vs 1.1% (difference 0.047; p = 0.0039); the excess was found below 30 mm, was small at 30–50 mm (difference 0.016; p = 0.078), and was absent at ≥50 mm (difference −0.004; p = 0.875). After sham-rate correction, 44% of bipolar channels with a detected late response had no expert N1. The findings indicate that expert N1 maps missed some late responses near stimulation in this sample, while the remote common-median responses were reference effects. Limits include 8 pulses per site, possible artifact or saturation in expert labels near stimulation, use of only the first clinical run from each patient, a post hoc bipolar analysis, and possible nonspecific late responses.

stereo-EEG · single-pulse electrical stimulation · evoked potentials · N1 · N2 · local bipolar reference · brain-computer interfaces · epilepsy