Chemical Heterogeneity of the Living Human Brain: A Proton MR Spectroscopy Study on the Effects of Sex, Age, and Brain Region

Brain chemistry was compared between 19 male and female normal volunteers in the age group 19-31 years, across six brain regions and nine metabolites using in vivo proton magnetic resonance spectroscopy. The relative concentrations of N-acetyl aspartate, choline, glutamate, glutamine, GABA, inositol, glucose, and lactate were measured relative to creatine within 8-cm(3) brain voxels. These measurements were performed in six brain regions: thalamus and cingulate, insula, sensorimotor, dorsolateral prefrontal, and orbital frontal cortices in the left hemisphere. Total metabolite concentration was highest in prefrontal regions (28% higher in orbital frontal cortex and 18.7% higher in dorsolateral prefrontal cortex compared with insula and thalamus, P < 10(-7)). Subjects 25-31 years of age demonstrated a significant increase in total metabolite concentration in the orbital frontal cortex (35%, P < 10(-7)) and sensorimotor cortex (16.7%, P < 10(-5)) compared to those 19-20 years of age. These two brain regions also showed gender dependence, with women demonstrating increased metabolite concentrations compared to men (9% increase in sensorimotor cortex, P < 0.002, and 2.1% in orbital frontal cortex). Most other brain regions showed no gender- or age-dependent differences. The results indicate that the living human brain is chemically heterogeneous. The chemical heterogeneity is sex and age dependent and specific for brain region.