Functional Abnormalities in Brain Areas That Mediate Autonomic Nervous System Control in Advanced Heart Failure

Abstract

Background Heart failure patients show substantial gray matter loss in brain areas that mediate autonomic control. Those injuries may lead to the aberrant autonomic patterns found in the syndrome. The purpose of this study was to determine if functional responses in the brain to an autonomic challenge would differ from normal patterns and would appear in areas of previously-demonstrated gray matter loss. Methods and Results We subjected 6 heart failure patients (left ventricular ejection fraction 0.15 ± 0.08; age 49 ± 12 years) and 16 controls (age 48 ± 11 years) to a forehead cold pressor challenge that would enhance sympathetic outflow and assessed functional magnetic resonance image signals over the entire brain during a 54-second baseline and 90-second challenge. Application of the cold stimulus elicited aberrant responses in the anterior and posterior hypothalamus, bilateral amygdala, hippocampus, cerebellar cortex, insular cortex, mid/posterior cingulate cortex, right ventral frontal cortex, and temporal and frontal cortices. Many of the areas neighbored or overlaid regions of previously demonstrated gray matter damage. Both classical autonomic control regions, as well as brain areas modulating these sites showed deficient responses, some of which appeared to be of an overdampened or underdampened nature. Conclusion The findings suggest that the earlier demonstrated changes in brain structure in heart failure result in aberrant functional neural responses; these dysfunctions may contribute to progression of the pathology in heart failure.