The heartbeat evoked potential and the prediction of functional seizure semiology

Functional seizures (FS) are common, and distinguishing FS from epileptic seizures (ES) can be challenging despite video telemetry (VT), and the pathophysiology is not well-understood. The heartbeat evoked potential (HEP) reflects the central processing of cardiac signals and bodily attention. Our group previously demonstrated that HEP amplitude may differentiate FS from ES. Here, we sought to replicate these HEP findings in an independent sample and test if HEP can characterise semiological subtypes of FS and ES. Lastly, we examined whether HEP modulation was associated with real-time bodily symptom reporting in functional and vasovagal syncope.

In a first study, we identified FS or ES from VT recordings of patients. We categorised FS and ES into “motile” or “non-motile” according to semiology with predominantly positive motor features, or with subjective sensory or negative motor features, respectively. HEP amplitude was calculated by averaging EEG segments time-locked to ECG R-waves, correcting for pre-R wave baseline, to quantify the average voltage between 0.455 and 0.595 seconds after the R wave. We compared HEP amplitude across FS and ES of equivalent semiology. For the second study, we quantified the HEP amplitude in patients with functional syncope and vasovagal syncope, from EEG recorded during head-up tilt procedure, focusing on reported symptom onset rather than the onset of clinical events.

Sixty-three and sixty individuals were included in study one and two, respectively. HEP amplitude distinguished FS from ES with matched semiology: In non-motile FS, HEP become more positive at the scalp from the interictal to preictal period, whereas in motile FS, the HEP became less positive at the scalp. ES were not associated with significant changes in HEP. In individuals with functional syncope, a more positive HEP was associated with reported bodily symptoms, but not for non-bodily (psychological or emotional) symptoms. In individuals with vasovagal syncope, a less positive HEP was associated with (most) bodily symptoms.

These findings indicate that FS semiology relates to patterns of bodily attention, as reflected by HEP amplitude change. Non-motile FS were associated with preictal increased HEP amplitude, suggesting greater bodily awareness, whereas motile FS showed a decrease in HEP amplitude. The increased HEP amplitude associated with bodily symptom reporting in functional syncope further supports a role for the HEP in tracking interoceptive processing and bodily attention. Together, this highlights the potential utility of the HEP as a marker for distinguishing FS from ES and for probing the interoceptive mechanisms underlying functional symptoms.