Dissociating Early Heartbeat-Evoked Afferent Gating From Late Associative Failure in Post-Anoxic Coma

Abstract Objective Following cardiac arrest and cardiopulmonary resuscitation, standard clinical EEG often fails to differentiate reversible metabolic depression from structural cortical necrosis. We evaluated whether the Heartbeat-Evoked Response (HER) can dissociate viable subcortical-cortical primary interoceptive afferent gating from non-viable distributed cortico-cortical networks in acute post-anoxic coma. Methods Continuous 19-channel EEG and synchronized Lead-II ECG recordings were analyzed across a harmonized multicenter cohort of 150 comatose post-cardiac arrest patients (discovery cohort: n = 100; independent validation cohort: n = 50; 58 Good Outcome [CPC 1–2] and 92 Poor Outcome [CPC 3–5]). Standardized Low-Resolution Electromagnetic Tomography (sLORETA) and non-linear Hilbert–Huang Transform (HHT) with Empirical Mode Decomposition (EMD) were applied to evaluate early (150–300 ms) versus late (350–500 ms) post-R-peak windows. Results Favorable recovery was associated with a preserved frontocentral negative deflection peaking at ~ 200 ms (-1.18 µV at electrode Fz), localized via sLORETA strictly to the anterior cingulate cortex (ACC; BA 24/32) and anterior insula. EMD isolated this early component into intermediate intrinsic modes (IMF 2–3; 8–16 Hz), yielding a sharp surge in instantaneous Hilbert energy (Et = 1.85 a.u.) and robust phase alignment (IPLV = 0.95). Non-survivors showed an anomalous positive shift (+ 1.45 µV), energy collapse (Et < 0.40 a.u.), and phase desynchronization (IPLV ≈ 0.18). In the late window (350–500 ms), both groups exhibited diffuse spatial dissipation and loss of discrete cortical generators. Conclusion Preserved early primary interoceptive afferent gating to the ACC/insula—rather than late associative network reverberation—serves as an objective electrophysiological biomarker of viable cortical microcircuitry in post-anoxic coma.

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Publication Details

Journal
Research Square
Published
2026-11-01
DOI
https://doi.org/10.21203/rs.3.rs-11341826/v1
Primary Topic
Cardiac Arrest and Resuscitation
Type
preprint
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preprint

Dissociating Early Heartbeat-Evoked Afferent Gating From Late Associative Failure in Post-Anoxic Coma

Raed Mualem, Calixto Machado, M Drobný, José Jesús Sánchez et al.
Research Square
Cardiac Arrest and Resuscitation
preprint

Dissociating Early Heartbeat-Evoked Afferent Gating From Late Associative Failure in Post-Anoxic Coma

Raed Mualem, Calixto Machado, M Drobný, José Jesús Sánchez, Beata Drobná Sániová⁴, Arthur Schiff³
preprint en

Abstract

Abstract Objective Following cardiac arrest and cardiopulmonary resuscitation, standard clinical EEG often fails to differentiate reversible metabolic depression from structural cortical necrosis. We evaluated whether the Heartbeat-Evoked Response (HER) can dissociate viable subcortical-cortical primary interoceptive afferent gating from non-viable distributed cortico-cortical networks in acute post-anoxic coma. Methods Continuous 19-channel EEG and synchronized Lead-II ECG recordings were analyzed across a harmonized multicenter cohort of 150 comatose post-cardiac arrest patients (discovery cohort: n = 100; independent validation cohort: n = 50; 58 Good Outcome [CPC 1–2] and 92 Poor Outcome [CPC 3–5]). Standardized Low-Resolution Electromagnetic Tomography (sLORETA) and non-linear Hilbert–Huang Transform (HHT) with Empirical Mode Decomposition (EMD) were applied to evaluate early (150–300 ms) versus late (350–500 ms) post-R-peak windows. Results Favorable recovery was associated with a preserved frontocentral negative deflection peaking at ~ 200 ms (-1.18 µV at electrode Fz), localized via sLORETA strictly to the anterior cingulate cortex (ACC; BA 24/32) and anterior insula. EMD isolated this early component into intermediate intrinsic modes (IMF 2–3; 8–16 Hz), yielding a sharp surge in instantaneous Hilbert energy (Et = 1.85 a.u.) and robust phase alignment (IPLV = 0.95). Non-survivors showed an anomalous positive shift (+ 1.45 µV), energy collapse (Et < 0.40 a.u.), and phase desynchronization (IPLV ≈ 0.18). In the late window (350–500 ms), both groups exhibited diffuse spatial dissipation and loss of discrete cortical generators. Conclusion Preserved early primary interoceptive afferent gating to the ACC/insula—rather than late associative network reverberation—serves as an objective electrophysiological biomarker of viable cortical microcircuitry in post-anoxic coma.

Research Square
Oranim Academic College of Education (IL), Emory University (US), Comenius University Bratislava (SK)
Good health and well-being
Cardiac Arrest and Resuscitation
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