The cross-sectional interplay between neurochemical profile and brain connectivity

Abstract

Neurochemical profile and brain connectivity are both critical aspects of brain function. However, our knowledge of their interplay across development is currently poor. We combined single-voxel magnetic resonance spectroscopy and resting functional magnetic resonance imaging in a cross-sectional sample spanning from childhood to adulthood which was reassessed in ~1.5 years (N = 293). We revealed the developmental trajectories of 20 neurochemicals in two key developmental brain regions (the intraparietal sulcus, IPS, and the middle frontal gyrus, MFG). We found that certain neurochemicals exhibited similar developmental trajectories across the two regions, while other trajectories were region-specific. Crucially, we mapped the connectivity of the brain regions IPS and MFG to the rest of the brain across development as a function of regional glutamate and GABA concentration. We demonstrated that glutamate concentration within the IPS is modulated by age in explaining IPS connectivity with frontal, temporal and parietal regions. In mature participants, higher glutamate within the IPS was related to more negative connectivity while the opposite pattern was found for younger participants. Our findings offer specific developmental insights on the interplay between the brain's resting activity and the glutamatergic system both of which are crucial for regulating normal functioning and are dysregulated in several clinical conditions.

Keywords: brain connectivity; development; glutamate; neurochemicals; parietal.

FIGURE 1

Positions of the two regions for the MRS displayed in a T1‐weighted image for (a) MFG, (b) IPS, are shown on sagittal and axial slices, respectively. Below each figure the mean spectrum form our sample at A1 of each region is shown (parts per million, ppm, in x‐axis), and the thickness corresponds to ±1 standard deviation from the mean. The middle panel shows the fit spectra of four neurochemicals, NAA (green), glutamate (black), GABA (red), and glutamine (cyan)

FIGURE 2

Glutamate concentration within the left intraparietal sulcus (IPS) was modulated by age in explaining the connectivity (Fisher‐z‐transformed correlation coefficient) between the IPS and seven regions. (a) superior frontal gyrus, (b) cingulate gyrus, (c) right angular gyrus, (d and e) right temporal gyrus, (f) left occipital/angular gyrus, and (g) left temporal gyrus. Dark blue regression lines correspond to +1 standard deviation (SD) above the mean age and light blue regression lines correspond to −1 SD from the mean age. To depict the interaction between the continuous variables (age and neurotransmitter concentration) we plotted the regression lines for ±1 SD from the mean age (Aiken, West, & Reno, 1991). Dark blue concerns +1 SD above the mean, while the light blue concerns −1 SD the mean and the shaded area represents 95% confidence intervals