Chemical network of the living human brain: Evidence of reorganization with aging

We recently described the chemical network properties of the human brain using in vivo proton magnetic resonance spectroscopy (¹H MRS). In a separate study of aging we found increased concentration of chemicals in the prefrontal and sensorimotor cortices up to the third decade of life, and subsequent decrease of chemical concentrations in the same brain regions after the third decade between young and middle age. We anticipated that these age-dependent differences in chemical concentrations might be a reflection of the chemical network reorganization of the brain during aging. The pattern of chemical connectivity within and across brain regions for all regional chemicals, and specific patterns of chemical connectivity for each chemical type were examined for young and middle age groups using ¹H MRS and correlation analysis. For all studied ages, the dominant positive correlations occurred within brain regions and negative correlations were seen across brain regions. However, the pattern of negative chemical connectivity across brain regions was weaker in middle-aged group (F=40.4, P<10^-7 comparing r-values between the two age groups, ANOVA). Within brain regions, the age effects on chemical correlations were seen in the cingulate cortex (46% decrease in the middle-aged group, F=7.2, P<0.007) and sensorimotor cortex (SMC) (27% decrease, F=8.9, P<0.003). Between brain regions, the age effects on chemical correlations were seen in the chemical interactions between the thalamus (433.3% increase in the middle-aged group, F=11.7, P<0.003), SMC (280% increase, F=20.1, P<10^-5), cingulate cortex (100.7% increase, F=21.3, P<10^-7), and other brain regions. We found also age-differential patterns of chemical connectivity across the studied brain regions for most chemical types. The results provide evidence that normal aging is associated with reorganization of chemical network of the human brain.