Age-related changes in baroreflex sensitivity and cardiac autonomic tone in children mirrored by regional brain gray matter volume trajectories

Abstract

BackgroundThe baroreflex and central autonomic brain regions together control the cardiovascular system. Baroreflex sensitivity (BRS) decreases with age in adults. Age-related changes in brain regions for cardiovascular control in children are unknown. We studied age-related changes in BRS, cardiac autonomic tone, and gray matter volume (GMV) of brain regions associated with cardiovascular control.MethodsBeat-to-beat blood pressure and heart rate (HR) were recorded in 49 children (6-14 years old). Spontaneous BRS was calculated by the sequence method. Cardiac autonomic tone was measured by spectral analysis of HR variability. GMV was measured using voxel-based morphometryin 112 healthy children (5-18 years old).ResultsAge-related changes in BRS were significantly different in children <10 years and ≥10 years. Age-related changes in GMV in regions of interest (ROI) were also significantly different between children <10 and ≥10 years and between children <11 and ≥11 years. However, age-related changes in cardiac autonomic tone were progressive.ConclusionsSignificant changes in BRS trajectories between <10 and ≥10 years may be associated with similar age-related changes of GMV in brain ROI. This new knowledge will guide future studies examining whether childhood cardiovascular disruption manifests as deviated maturation trajectories of specific brain regions.

Figure 1

Age-related changes in baroreflex sensitivity (BRS) for increasing (A) and decreasing (B) blood pressure with 95% confidence intervals. Age-related changes in BRS were significantly different between children <10 and ≥10 years. BRS progressively increased with age in children <10 years and reduced in children ≥10 years.

Figure 2

Age-related changes in cardiac autonomic tone for low frequency (LF) (A) and high frequency (HF) (B) regimes and the LF/HF ratio (C). LF and HF outcomes progressively decreased with age, while LF/HF increased with age, without significant change in slope at 10 years.

Figure 3

Clusters of voxels with significant change in gray matter volume with age in children <10 and ≥10 years of age. Hot colors indicate increased and cool colors indicate decreased age-related changes in children ≥10 years. Clusters are restricted to regions of the brain associated with autonomic and cardiovascular functions including posterior cingulate (A), amygdala (B), midbrain (C), pons (D), putamen (E), and hypothalamus (F). Montreal Neurological Institute (MNI) coordinate for each brain slice is shown above each image and slice locations are indicated in the sagittal view. Axial slices are shown in neurological convention (right side of brain=right side of image). Clusters are significant at p<0.1, family-wise error corrected, after thresholding at nominal T > 2.85.

Figure 4

Clusters of voxels with significant change in gray matter volume with age in children <11 and ≥11 years. Hot colors indicate increased and cool colors indicate decreased age-related changes in children ≥11 years. Clusters are significant at p<0.1, family-wise error corrected, after thresholding at nominal T > 2.85, restricted to ROI known for essential role in cardiovascular regulation. Clusters are labeled as follows: caudate (A), posterior cingulate (B), amygdala (C), inferior orbital frontal (D), midbrain (E), putamen (F), hypothalamus (G), right hippocampus (H), and left posterior insula (I). Montreal Neurological Institute (MNI) coordinate for each brain slice is shown above each image and slice locations are indicated in the sagittal view. Axial slices are shown in neurological convention (right side of brain=right side of image).

Figure 5

Age-related changes in gray matter volume (GMV) in left posterior insula (A), left putamen (B), right amygdala (C), and right hippocampus (D). Note that age-related changes in GMV shown are for the voxel of peak significance in each region for the difference between children <11 and ≥11 years.