Recovery of consciousness after severe brain injury: The role of arousal regulation mechanisms and some speculation on the heart-brain interface

SPECULATIONS ON THE IMPORTANCE OF HEART-BRAIN RESEARCH IN FUTURE STUDIES OF RECOVERY OF CONSCIOUSNESS

As this conference is focused on the heart-brain interface, it is appropriate to consider the relevance of heart-brain research to the general set of problems reviewed above. In fact, the linkage is quite natural, and classical physiologic psychology research has shown that cerebral arousal regulation is associated with patterned modulation of cardiac rhythm and autonomic function linked to the behavioral state.^48,49 Among the most relevant observations are demonstrations that sustained focused attention is associated with several stereotyped cardiac and autonomic changes, including anticipatory bradycardia,^50,51 pupillary dilatation, ⁵² and others (eg, galvanic skin response). Neurologic cases have shown that such couplings of effort to reflex bradycardia, pupillary dilatation, and other autonomic markers are altered by focal cerebral lesions in the right frontal lobe⁵³ and left anterior cingulate cortex.⁵⁴

In the single-subject central thalamic DBS study reviewed above,⁴³ there were several unpublished observations that are potentially relevant to these mechanisms. During initial bedside testing of the individual DBS electrode contacts in first 2 postoperative days, electrical stimulation above threshold voltages associated with visible arousal response (for details, see supplementary material in Schiff et al⁴³) consistently produced marked changes in heart rate and audible modulations of heart rhythm during interactions with the patient. Notably, the patient’s basal heart rate rose from a stable level of approximately 50 to 55 beats per minute to approximately 70 to 75 beats per minute—a nearly 50% increase. While increases in blood pressure and heart rate typically accompany arousal, the heart rate change observed here may reflect a marked change in cerebral metabolic rates. Earlier quantitative FDG-PET imaging in this patient revealed a global metabolic rate across the brain of approximately half the normal level.⁴⁶ Considering that the brain consumes approximately 23% of the cardiac output,⁵⁵ the increased heart rate observed in this setting may reflect an increase in demand in cardiac output, possibly as much as 100%. At the same time that these changes occurred, there was an audible cardiac deceleration noted when the patient was attentionally engaged by the examiner (this occurred without scoreable variation in most of the quantitative neurobehavioral metrics; see supplementary material in Schiff et al⁴³). Of note, although the patient had suffered a complex severe brain injury, the right ventral frontal lobe showed the largest structural lesion⁴⁶; injuries to the right hemisphere are associated with loss of such anticipatory changes in heart rate during attentional task performance.⁵³

These anecdotal observations suggest that future studies that include measures to track patterns of heart rate variation during recovery of consciousness might provide an indirect index of increasing brain demand for allocation of cardiac output or emergent neural control of mechanisms linking cardiovascular response to attentive behavior. Ongoing coupling of electroencephalographic measures to autonomic and basal cardiac rhythms may be particularly interesting to examine during social interactions,⁵⁶ as it is likely that behavioral responsiveness is linked to social stimuli. Emotional reactivity has been proposed as an essential component of arousal per se,⁴⁹ and although not formally studied in the DBS trial reviewed above, emotional reengagement seems to be a clear concomitant of the collection of gestural and verbal behavioral improvements operationally tracked using quantitative behavioral scales. Beyond tracking heart-brain interactions as an index of brain recovery, it is possible that the integrity of heart-brain interactions may also be a target for optimization in support of recovery of consciousness after nonprogressive brain injury. Moreover, studies of optimization of cardiac function in severely brain-injured patients may provide insight into the recovery process as well.