Coronary artery disease affects cortical circuitry associated with brain-heart integration during volitional exercise.

This study tested the hypothesis that coronary artery disease (CAD) alters the cortical circuitry associated with exercise. Observations of changes in heart rate (HR) and in cortical blood oxygenation level-dependent (BOLD) images were made in 23 control subjects [control; 8 women; 63 ± 11 yr; mean arterial pressure (MAP): 90 ± 9 mmHg] (mean ± SD) and 17 similarly aged CAD patients (4 women; 59 ± 9 yr; MAP: 87 ± 10 mmHg). Four repeated bouts each of 30%, 40%, and 50% of maximal voluntary contraction (MVC) force (LAB session), and seven repeated bouts of isometric handgrip (IHG) at 40% MVC force (fMRI session), were performed, with each contraction lasting 20 s and separated by 40 s of rest. There was a main effect of group (P = 0.03) on HR responses across all IHG intensities. Compared with control, CAD demonstrated less task-dependent deactivation in the posterior cingulate cortex and medial prefrontal cortex, and reduced activation in the right anterior insula, bilateral precentral cortex, and occipital lobe (P < 0.05). When correlated with HR, CAD demonstrated reduced activation in the bilateral insula and posterior cingulate cortex, and reduced deactivation in the dorsal anterior cingulate cortex, and bilateral precentral cortex (P < 0.05). The increased variability in expected autonomic regions and decrease in total cortical activation in response to the IHG task are associated with a diminished HR response to volitional effort in CAD. Therefore, relative to similarly aged and healthy individuals, CAD impairs the heart rate response and modifies the cortical patterns associated with cardiovascular control during IHG.

Forebrain organization for autonomic cardiovascular control.

This brief review discusses the current state of knowledge regarding the cortical circuitry associated with autonomic cardiovascular responses to volitional exercise in conscious humans. Studies to date have emphasized the autonomic nervous system adjustments that occur through top-down central command features as well as bottom-up signals arising from skeletal muscle. While in its infancy, the pattern of cortical circuitry associated with exercise seem to depend on the nature of the exercise but with common patterns arising in the insula cortex, dorsal anterior cingulate cortex, medial prefrontal cortex, and hippocampus.

Evidence for a medial prefrontal cortex-hippocampal axis associated with heart rate control in conscious humans.

Cardiovascular arousal correlates to activity within the medial prefrontal cortex (MPFC). Additional evidence provides anatomical and functional links between the MPFC and hippocampus (HC). This study tested the hypothesis that the MPFC and HC form a sub-network associated with rapid heart rate (HR) responses to volitional effort. Primary analyses were performed on 29 individuals (18 males) ranging from 21 to 80 years of age, who produced a HR response >3bpm to an isometric handgrip (IHG) task. HR and cortical activity were recorded using functional magnetic resonance imaging with blood oxygen level-dependent contrast. The average change in HR from baseline was 6bpm ±2. Activity in the MPFC and left HC was reduced relative to baseline in all subjects when correlated with the HR time course. Measures of connectivity demonstrated that the MPFC engaged in significantly stronger functional connectivity to the left HC during a 40% IHG task. Effective connectivity revealed a directionality of influence from the MPFC to the left HC. A second group (n=15) of individuals without a HR response (~1bpm) to IHG were studied post-hoc and these individuals showed no deactivation in either the MPFC or left HC. These results suggest the presence of a MPFC-HC axis that participates in the neurally-mediated HR response to exercise.

Low-frequency oscillations in R-R interval and blood pressure across the continuum of cardiovascular risk.

The purpose of this study was to assess the power and the frequency of low-frequency (LF; 0.04-<0.15 Hz) oscillations in systolic blood pressure (SBP) and R-R interval (RRi) across the continuum of risk of cardiovascular disease, including age. A potential confound in such determinations is low spontaneous breathing frequency in some individuals. We measured beat-to-beat SBP, RRi and respiration in healthy YOUNG (33±3 years) and OLDER subjects (62±5 years) and older patients with hypertension (HT, 61±5 years), coronary artery disease without (CAD, 62±5 years) and with type 2 diabetes (CAD+DM, 62±4 years, n=28 for all groups) during spontaneous breathing at supine rest. Power (Power(LF)) and median frequency (Med(LF)) of LF oscillations were calculated by power spectral analysis after removing respiratory effects by least-mean-square adaptive filtering. OLDER had higher Power(LF-SBP) (5.5±3.0 vs. 3.4±2.5 mmHg(2), p=0.002) and lower Power(LF-RRi) than YOUNG (339±460 vs. 575±422 ms(2), p=0.001) whereas neither variable differed between OLDER and patient groups. Med(LF-SBP) (0.072±0.009 vs. 0.080±0.011 Hz, p=0.005) and Med(LF-RRi) (0.072±0.010 vs. 0.079±0.013 Hz, p=0.027) were lower in OLDER compared with YOUNG. Compared with OLDER, Med(LF-RRi) was lower in CAD (0.065±0.006 Hz, p=0.015) and CAD +DM (0.066±0.008 Hz, p=0.012); whereas CAD+DM had also lower Med(LF-SBP) (0.065±0.006 Hz, p=0.012). No differences were observed between OLDER and HT and between CAD and CAD+DM in these variables. We concluded that age is major determinant of the power of LF oscillations in SBP and RRi at rest, whereas the median frequency of these oscillations is altered also by coronary artery disease.