A cortical potential reflecting cardiac function

Abstract

Emotional trauma and psychological stress can precipitate cardiac arrhythmia and sudden death through arrhythmogenic effects of efferent sympathetic drive. Patients with preexisting heart disease are particularly at risk. Moreover, generation of proarrhythmic activity patterns within cerebral autonomic centers may be amplified by afferent feedback from a dysfunctional myocardium. An electrocortical potential reflecting afferent cardiac information has been described, reflecting individual differences in interoceptive sensitivity (awareness of one's own heartbeats). To inform our understanding of mechanisms underlying arrhythmogenesis, we extended this approach, identifying electrocortical potentials corresponding to the cortical expression of afferent information about the integrity of myocardial function during stress. We measured changes in cardiac response simultaneously with electroencephalography in patients with established ventricular dysfunction. Experimentally induced mental stress enhanced cardiovascular indices of sympathetic activity (systolic blood pressure, heart rate, ventricular ejection fraction, and skin conductance) across all patients. However, the functional response of the myocardium varied; some patients increased, whereas others decreased, cardiac output during stress. Across patients, heartbeat-evoked potential amplitude at left temporal and lateral frontal electrode locations correlated with stress-induced changes in cardiac output, consistent with an afferent cortical representation of myocardial function during stress. Moreover, the amplitude of the heartbeat-evoked potential in the left temporal region reflected the proarrhythmic status of the heart (inhomogeneity of left ventricular repolarization). These observations delineate a cortical representation of cardiac function predictive of proarrhythmic abnormalities in cardiac repolarization. Our findings highlight the dynamic interaction of heart and brain in stress-induced cardiovascular morbidity.

Fig. 1.

Stress-induced changes in physiological variables. Mental stress induced by serial subtraction task was associated with significant increases in systolic blood pressure, heart rate, and ejection fraction. Mean changes in physiological parameters across all subjects are presented.

Fig. 2.

ECG amplitude during baseline and stress task conditions. ECG was measured at six locations around the base of the neck. No significant differences in ECG amplitude were observed during the post-T-wave epoch (140 ms average from 455 to 595 ms after R wave).

Fig. 3.

HEPs during stress and baseline conditions. Mental stress was not associated with significant alteration in HEP amplitude. (A) HEPs at all scalp locations are shown for both the baseline (blue) and mental stress (red) conditions. In all graphs, up represents positive ERP deflections. (B) HEPs at standard 10/20 international electrode placement system positions are enlarged. In addition, HEP epochs (140 ms centered at 525 ms after R wave) are highlighted by green bars. (Left) Left hemisphere electrodes. (Right) Right hemisphere electrodes. (C) Average ERP difference waveforms displayed in 2D scalp space. Across subjects, no significant alterations in HEPs were observed during mental stress. Greater negative HEPs during the high-stress condition are illustrated toward the blue end of the spectrum, whereas greater positive HEPs during the high-stress condition are shown toward the red end of the spectrum.

Fig. 4.

Association between HEPs and cardiac output. Stress-induced change in cardiac output was significantly correlated with change in HEP amplitude within left temporal and posterior frontal electrode locations. (A) T statistics reflecting the level of association between changes in HEPs and cardiac output are presented on a 3D scalp map. Individual electrodes are significant at P < 0.001. Each circled cluster is also significant at P = 0.001 (cluster level P value correction). (B) Cortical potentials for all subjects are presented at a representative electrode from within each significant cluster. The cortical waveforms during baseline (blue) and stress (red) conditions are illustrated, whereas HEP epochs are indicated by green bar differences (140 ms average from 455 to 595 ms after R wave). Across subjects, increased HEP negativity was associated with increased cardiac output during stress. (Upper) Electrode 100. (Lower) Electrode 118. (Left) HEP. (Right) HEP and cardiac output correlation.

Fig. 5.

Association between HEPs and cardiac repolarization inhomogeneity. Stress-induced change in myocardial repolarization (Hill parameter) was significantly correlated with change in HEP amplitude within left temporal electrode locations. (A) T statistics reflecting the level of association between changes in HEPs and repolarization inhomogeneity are presented on a 3D scalp map. Individual electrodes are significant at P < 0.002, whereas the circled cluster is significant at P = 0.032 (cluster level P value correction). (B) Cortical potentials for all subjects are presented at two representative electrodes. The cortical waveforms during baseline (blue) and stress (red) conditions are illustrated, whereas HEP epochs are indicated by green bar differences (140 ms average from 455 to 595 ms after R wave). Across subjects, increased HEP negativity was associated with increased inhomogeneity of myocardial repolarization. (Upper) Electrode 104. (Lower) Electrode 121. (Left) HEP. (Right) HEP and Hill parameter correlation.