The heartbeat-locked SEEG residual showed no evidence of insula specificity in 25 patients

This study tested whether the heartbeat-locked SEEG residual after ECG regression is larger at insula contacts, as expected for an insula-specific neural heartbeat-evoked response. It reanalyzed an archived table of 3,095 bipolar pairs from 31 ds004100 patients, using Harvard-Oxford atlas labels and patient-level sign-flip tests. The primary comparison included 109 insula pairs in 25 patients. The mean patient difference (insula minus other pairs) in residual z score was -0.362 (95% CI -0.79 to +0.08; p = 0.133; Holm p = 0.265). For residual minus pseudo-beat control, the mean difference was -0.239 (95% CI -0.73 to +0.22; p = 0.360). The preregistered rule therefore found no evidence for insula specificity. Against other cortical pairs, the mean difference was -0.02 (95% CI -0.43 to +0.42). Strict midpoint-labeled insula pairs had a smaller residual than other pairs (mean difference -0.76; Holm p = 0.0006). In a post hoc analysis, the largest residual was at 181 pairs outside the template brain (22 patients; mean difference +1.84, 95% CI +1.05 to +2.70; p = 0.0001). This pattern is compatible with extracerebral sources, artifact, or localization error. The results do not support a neural insula response as the source of the residual, but do not exclude a small neural response that bipolar SEEG cannot resolve at template resolution. Limitations include template-space rather than patient anatomy coordinates, possible label errors of several millimeters, 300 seconds of data per patient from one ECG lead, drug-resistant epilepsy, and only 25 patients with insula pairs.

SEEG · heartbeat-evoked response · insula · ECG regression · epilepsy · neurophysiology · Harvard-Oxford atlas