Study Objectives:. Determine whether obstructive sleep apnea (OSA) subjects show indications of axonal injury.Design:. We assessed fiber integrity in

Heart failure (HF) patients exhibit enhanced sympathetic tone, aberrant responses to blood pressure challenges, and sleep-related breathing disorders, suggesting that the syndrome is accompanied by central neural deficits. We assessed regional gray matter volumes over the entire brain in nine HF patients (51 ± 10 yr; left ventricular ejection fraction 0.27 ± 0.06; six men) and 27 healthy controls (46 ± 12 yr; 22 men) using T1-weighted magnetic resonance imaging to evaluate potential neural damage. Regional volumes were evaluated by using voxel-based morphometry while controlling for age, gender, and handedness. HF patients showed significant and largely lateralized gray matter loss in autonomic and respiratory-related areas as well as regions not classically associated with such control, including the insula and basal ganglia, right cingulate gyrus, parahippocampal/fusiform gyrus, dorsal midbrain extending to the posterior and medial thalamus, ventral and superior lateral frontal cortex, bilateral cerebellar quadrangular lobules and right fastigial and neighboring nuclei, and bilateral deep parietal and lateral parietal-occipital cortex. Areas of gray matter loss may contribute to inappropriate cognitive, autonomic, and breathing regulation in HF.

Obstructive sleep apnea (OSA) patients exhibit altered sympathetic outflow, which may reveal mechanisms underlying the syndrome. We used functional MRI (fMRI) in 16 control and 10 OSA subjects who were free of cardiovascular or mood-altering drugs to examine neural responses to a forehead cold pressor challenge, which elicits respiratory slowing, bradycardia, and enhanced sympathetic outflow. The magnitude of cold-induced bradycardia was smaller, and respiratory slowing showed greater intersubject variability and reached a nadir later in OSA patients. Both groups showed similar signal changes to cold stimulation in multiple brain sites. However, signal increases emerged in OSA over controls in anterior and posterior cingulate and cerebellar and frontal cortex, whereas signals markedly declined in the ventral thalamus, hippocampus, and insula rather than rising as in controls. Anomalous responses often paralleled changes in breathing and heart rate. Medullary, midbrain areas and lentiform and cerebellar dentate nuclei also showed lower signals in OSA cases. Cold pressor physiological responses are modified in OSA and may result from both diminished and exaggerated responses in multiple brain structures.