Cardiovascular arousal is associated with patterned cortical activity changes. Head-down-tilt bed rest (HDBR) dimishes the baroreflex-mediated cardiac control. The present study tested the hypothesis that HDBR deconditioning would modify the forebrain organization for heart rate (HR) control during baroreflex unloading. Heart rate variability (HRV), blood pressure and plasma hormones were analysed at rest, whereas HR and cortical autonomic activation patterns (functional magnetic resonance imaging) were measured during graded and randomly assigned lower body negative pressure treatments (LBNP, -15 and -35 mmHg) both before (Pre) and after (Post) a 24 h HDBR protocol (study 1; n = 8). An additional group was tested before and following diuretic-induced hypovolaemia (study 2; n = 9; spironolactone, 100 mg day(-1) for 3 days) that mimicked the plasma volume lost during HDBR (-15% in both studies; P