Impaired Cerebellar and Limbic Responses to the Valsalva Maneuver in Heart Failure

Abstract

Heart failure (HF) patients show an inability to regulate autonomic functions, a characteristic which is associated with increased mortality. These autonomic deficits may stem from earlier demonstrated injury to central autonomic regulatory areas, providing a structural basis for the autonomic abnormalities. However, knowledge of structural injury provides insufficient insights into timing and magnitude of signal patterns within affected areas which lead to impaired autonomic outflow. Among damaged brain areas, cerebellar sites are key for timely coordination of sympathetic and parasympathetic attributes, and for dampening extremes of hypotension and hypertension induced by other injured sites, including hypothalamic and limbic areas. We collected functional magnetic resonance imaging (fMRI) signals in cerebellar and limbic areas to characterize amplitude and timing patterns of neural responses to the Valsalva maneuver, an autonomic challenge that elicits sequential sympathetic and parasympathetic responses, in 16 HF patients and 33 control subjects. HF patients showed distorted fMRI signal patterns during the challenge period in the cerebellar vermis, left cerebellar crus II, and left insula, whereas the right crus II and insula, and bilateral amygdalae showed normal patterns. However, all structures, except the left crus II, showed altered responses in HF during the recovery period. Crus II patterns reflected a failure of HF subjects to demonstrate the normal lateralized responses, while in the insula, HF subjects exhibited abnormal left-right patterns, relative to controls. The abnormal timing and response patterns in these injured areas critical for autonomic regulation likely contribute to the enhanced sympathetic outflow and autonomic dysfunction characteristic of HF.