Marked changes in brain physiology and structure take place between childhood and adulthood, including changes in functional connectivity and changes in the balance between main excitatory and inhibitory neurotransmitters glutamate (Glu) and GABA. The balance of these neurotransmitters is thought to underlie neural activity in general and functional connectivity networks in particular, but so far no studies have investigated the relationship between human development related differences in these neurotransmitters and concomitant changes in functional connectivity. GABAϩ/H 2 O and Glu/H 2 O levels were acquired in a group of healthy children, adolescents, and adults in a subcortical (basal ganglia) region, as well as in a frontal region in adolescents and adults. Our results showed higher GABAϩ/ Glu with age in both the subcortical and the frontal voxel, which were differentially associated with significantly lower Glu/H 2 O with age in the subcortical voxel and by significantly higher GABAϩ/H 2 O with age in the frontal voxel. Using a seed-to-voxel analysis, we were further able to show that functional connectivity between the putamen (seed) and other subcortical structures was lower with age. Lower subcortical Glu/H 2 O with age mediated the lower connectivity in the dorsal putamen. Based on these results, and the potential role of Glu in synaptic pruning, we suggest that lower Glu mediates a reduction of local connectivity during human development.
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