Authors :
Presenting Author: Yilun Zhou, MS – Yale University
Kelly Pu, BS – Duke University
Cindy Mei, BS – Yale University
Robert Duckrow, MD – Yale University
Dennis Spencer, MD – Yale University
Hitten Zaveri, PhD – Yale School of Medicine, New Haven, CT, USA
Adithya Sivaraju, MD – Yale New Haven Hospital
Rationale:
Accurate localization of the seizure onset zone (SOZ) remains challenging in focal epilepsy, with variable surgical outcomes. Cortico-cortical evoked potentials (CCEPs) provide high-resolution connectivity mapping, but optimal metrics for distinguishing epileptogenic tissue remain unclear. Previous studies suggest distance-dependent connectivity patterns exist in cortical networks, yet their specific characteristics within epileptogenic regions are poorly understood. We hypothesized that SOZ exhibit distinct distance-dependent connectivity patterns compared to non-SOZ regions.
Methods:
Six patients with drug-resistant focal epilepsy underwent intracranial electroencephalography monitoring with CCEP testing. Bipolar stimulation (1 Hz, 10 mA) was performed between adjacent electrode contacts, with responses recorded from all available sites. N2 components were identified using automated algorithms, and area under the curve (AUC) values were quantified, log-transformed, and normalized to capture both response magnitude and duration. Electrode locations were mapped to Yale Brain Atlas parcels, and Euclidean distances between stimulation-recording sites were computed. Piecewise regression models with a 25mm inflection point characterized distance-AUC relationships, enabling statistical comparisons between SOZ/peri-SOZ and non-SOZ regions.
Results:
Analysis of 14,899 stimulation-recording combinations revealed a distinct two-phase relationship between N2 AUC and distance, with an inflection point at 25mm separating short-range and long-range connections. Short-range connections (< 25mm) exhibited steep negative slopes (slope = -0.01084 ± 0.00077), while long-range connections ( >25mm) showed more gradual decay (slope = -0.00142 ± 0.00004, p < 0.001). Critically, SOZ and peri-SOZ regions demonstrated significantly steeper short-range decay (-0.01350 ± 0.001) compared to non-SOZ regions (-0.00936 ± 0.001, p < 0.001). Binned analyses confirmed significant differences across multiple distance ranges (0-12.5mm, 12.5-25mm, 25-37.5mm, 75-87.5mm, 87.5-100mm; p< 0.05, Mann-Whitney U test).