RESUMEN
To investigate whether the observed anisotropic diffusion in cerebral cortex may reflect its columnar cytoarchitecture and myeloarchitecture, as a potential biomarker for disease-related changes, we compared postmortem diffusion magnetic resonance imaging scans of nine multiple sclerosis brains with histology measures from the same regions. Histology measurements assessed the cortical minicolumnar structure based on cell bodies and associated axon bundles in dorsolateral prefrontal cortex (Area 9), Heschl's gyrus (Area 41), and primary visual cortex (V1). Diffusivity measures included mean diffusivity, fractional anisotropy of the cortex, and three specific measures that may relate to the radial minicolumn structure: the angle of the principal diffusion direction in the cortex, the component that was perpendicular to the radial direction, and the component that was parallel to the radial direction. The cellular minicolumn microcircuit features were correlated with diffusion angle in Areas 9 and 41, and the axon bundle features were correlated with angle in Area 9 and to the parallel component in V1 cortex. This may reflect the effect of minicolumn microcircuit organisation on diffusion in the cortex, due to the number of coherently arranged membranes and myelinated structures. Several of the cortical diffusion measures showed group differences between MS brains and control brains. Differences between brain regions were also found in histology and diffusivity measurements consistent with established regional variation in cytoarchitecture and myeloarchitecture. Therefore, these novel measures may provide a surrogate of cortical organisation as a potential biomarker, which is particularly relevant for detecting regional changes in neurological disorders.
RESUMEN
Previous studies have found alterations in the columnar organization of the cortex in autism spectrum disorders. Such changes have been suggested to be limited to higher order association areas and to spare primary sensory areas. In addition, evidence from gene-expression studies have suggested that there may be an attenuation of cortical differentiation in autism spectrum disorders. The present study specifically assessed the minicolumns of cells that span the depth of the cortex in a larger sample of autism spectrum disorder cases than have been studied previously, and across a broad age range. The cortical regions to be investigated were carefully chosen to enable hypotheses about cortical differentiation and the vulnerability of association cortex to be tested. Measures of the minicolumnar arrangement of the cortex (minicolumn width, spacing and width of the associated axon bundles) were made in four regions of cortex (primary auditory cortex, auditory association cortex, orbital frontal cortex and inferior parietal lobe) for 28 subjects with autism spectrum disorder and 25 typically developing control subjects. The present study found wider minicolumns in autism spectrum disorder [F(1,28) = 8.098, P = 0.008], which was particularly pronounced at younger ages, providing evidence for an altered developmental trajectory at the microstructural level. In addition, altered minicolumn width was not restricted to higher order association areas, but was also seen in the primary sensory region investigated. Finally, this study found evidence that cortical regional differentiation was still present in autism spectrum disorder [F(3,39) = 5.486, P = 0.003], although attenuated compared to typically developing subjects [F(3,45) = 18.615, P < 0.001]. It is suggested that wider spacing of the minicolumns may relate to the enhanced discrimination seen in some individuals with autism spectrum disorders.
