The next significant contribution was the report of minicolumn abnormalities in autism.7 Prior to this, there were no substantive histopathologic abnormalities reported in the cerebral cortex in autism, though all behavioral neurological evidence pointed to it as a primary site of brain dysfunction. Minicolumns are composed of radially oriented arrays of pyramidal neurons (layers II-VI), interneurons (layers I-VI), axons, and dendrites. Minicolumns assemble into macrocolumns, which form receptive fields. Minicolumns have been hypothesized to be the smallest radial unit of information processing in the cortex, but this function has not been confirmed. In autism, minicolumns have been reported to be increased in number and narrower in width, with reduced neuropil space, with smaller neuron cell bodies and nucleoli (Figure 2).7 These abnormalities have been observed bilaterally in cortical areas 3, 4, 9, 17, 21, and 22. The description of these cortical abnormalities provided a critical counterbalance to the numerous reports of increased white matter volume, which might otherwise have led to a white matter model of autism. Second, the minicolumn abnormality provided a potential unifying link between gray and white matter abnormalities in autism, in that evolutionary evidence predicted an increase in white matter projections with an increasing number of minicolumns to maintain cortical connectivity.7 Diffusion tensor tracking data have documented an increase in pathway volume and fiber number even in the absence of increased total brain volume, eg, in adults with autism, thus providing evidence of the persistence of the predicted increase in fiber number (Figure 3) (C. D. Smith and T. E. Conturo, unpublished data, September 2005).