Sex differences in N-acetylaspartate correlates of general intelligence: an 1H-MRS study of normal human brain

Researchers have long attempted to determine brain correlates of intelligence using available neuroimaging technology including CT, MRI, PET, and fMRI. Although structural and functional imaging techniques are well suited to assess gross cortical regions associated with intelligence, the integrity and functioning of underlying white matter networks critical to coordinated cortical integration remain comparatively understudied. A relatively recent neuroimaging advance is magnetic resonance spectroscopy (MRS) which allows for interrogation of biochemical substrates of brain structure and function in vivo. In this study, we examined twenty-seven normal control subjects (17 male, 10 female) to determine whether N-acetylaspartate (NAA), a metabolite found primarily within neurons, is related to intelligence as assessed by the Wechsler Adult Intelligence Scale-III. Of the three white matter regions studied (i.e., left frontal, right frontal, left occipito-parietal), we found that a model including only left occipito-parietal white matter predicted intellectual performance [F(1,25) = 8.65, P = .007; r2 = .26], providing regional specificity to our previous findings of NAA-IQ relationships. Moreover, we found that a complex combination of left frontal and left occipito-parietal NAA strongly predicted performance in women, but not men [F(2,7) = 21.84, P < .001; adjusted r2 = .82]. Our results highlight a biochemical substrate of normal intellectual performance, mediated by sex, within white matter association fibers linking posterior to frontal brain regions.