Methodologies to Detect Cortico-Cortical Evoked Potentials: A Systematic Review

Tamara Al-Sadek^1*Aryan Wadhwa²Millen Wadhwa²Aaron E L Warren²John D Rolston²

• ¹American University of Beirut, Beirut, Lebanon
• ²Brigham and Women's Hospital, Boston, United States

Cortico-cortical evoked potentials (CCEPs) are electrophysiological responses elicited by direct electrical stimulation of one cortical region and recorded from another, providing insights into functional connectivity and effective communication pathways between brain areas. However, no consistent standard for defining and measuring CCEPs currently exists. In this study. we sought to systematically review the CCEP literature on detection methods to evaluate commonalities and gaps in methodology. We extracted demographic data, disease, recording type, montage, recording system, stimulation amplitude and frequency, time window used for epoching around stimulus onset, whether data was open access, and detection approach. Over half of the 187 studies undergoing full text review lacked a description of the CCEP detection method. Specifically, 9.1% utilized visual identification, whereas 49.74% did not explicitly state it. The remaining 72 studies represented 3,424 patients, of whom 58.3% had sEEG electrodes and most had epilepsy. Most common detection method was threshold-based (68.1%), followed by statistical testing (16.7%) to determine if CCEPs are significantly different from baseline, data-driven methods (4.1%) that quantify responses after learning from data, and frequency-based approaches (4.1%). Bipolar (48.6%) and single-electrode referential montages (18.1%) were most commonly utilized. CCEP detection methods lack consensus, with many omitting methodological details and relying on threshold-based techniques, assuming fixed response shapes. Future studies should encourage data-driven approaches, which learn directly from data, offer a more robust alternative and improve quantification in both clinical and research settings.