Cortical Organization in the Brains of Autistic Subjects: A Correlation Between Pyramidal Cell Size and Core Minicolumnar Width

Background: Autism is a condition where both minicolumnar and cell soma size have been described as being smaller than normal.

Objectives: We hypothesize that the smaller cell bodies in autism are not pathological; but rather, a required feature of a law of conservation relating the dimensions of pyramidal cell size and numbers to minicolumnar size.

Methods: Postmortem tissue was obtained from eight donors with autism spectrum disorders and ten neurotypical comparison clients. Digital micrographs were obtained from a single section covering the full cortical depth (lamina II–VI) in each of Brodmann areas 3, 4, 9, 10, 11, 17, 18, 20, 21, 22, 24, 37, 43, 44, 45, and 47. Minicolumnar width w and the cross section of pyramidal cells comprising the minicolumn were estimated using our established computerized image analysis methodology. Pyramidal cell cross section was transformed to the equivalent diameter d_eq of a circle with the same area in order to have the same dimensions as w. Statistical analysis used a mixed effects model with d_eq as a linear function of w along with Brodmann area and lamina (II–VI) and all interactions between those effects. The intercept of the model was random over individual cases, nested within diagnostic category (autistic or neurotypical).

Results: Average d_eq increased with w at a rate of 0.097 (F_1,1187 = 2417; p < 0.0001), averaging over all lamina and Brodmann areas. The rate of increase is not constant across different brain regions, however (F_15,1187 = 17.0; p < 0.0001). There was no significant dependence on diagnostic category (χ² < 0.0001, p = 0.9995). Mean d_eq was 15.3 μm (s.d. 1.9 μm) in autism and 15.6 μm (s.d. 1.5 μm) in comparison clients, while mean w was 44.9 μm (s.d. 4.5 μm) in autism and 46.0 μm (s.d. 4.2 μm) in neurotypical cases.

Conclusions: The resultant phenotype (i.e., smaller cell bodies) engenders a bias that favors short corticocortical connections as opposed to long connections. The fact that a law of conservation apparently mediates cell soma size in autism suggests that this aspect of the described minicolumnopathy occurs within an isolated system thus emphasizing the neurodevelopmental origin of the condition.