Table 27-1 lists the reported anatomic brain abnormalities found in ASD. Abnormalities in cortical white22-25 and gray24,26,27 matter, the limbic system,28-31 particularly the hippocampus and amygdala,32,33 as well as in the cerebellum,24,26,28,34 have been reported. The functional and developmental significance of these neuropathologic abnormalities has led to speculation regarding pathogenic mechanisms underlying ASD. The reduced number of Purkinje cells in the cerebellum with few significant changes in the inferior olive may point to a prenatal onset.28 The abnormally increased white matter volume has been proposed to be the result of an increase in the short association fibers in the frontal and temporal lobes due to an increased number of microcolumns.22 This, in turn, has been proposed to result in too much intracortical communication, an imbalance between local and distant cortical communication, and a deficit in large-scale cortical integration that is required for high-order cognitive processes such as language, behavioral regulation, and context-based social interactions. Abnormalities of the amygdala have been linked to abnormal fear conditioning in animal models.35 Clearly ASD is associated with widespread abnormalities of brain development, but the timing, localization, and links between these abnormalities are still not known. In addition, the connection between these neuropathologic findings and the derailment of cognitive development is a matter of intense debate. As discussed next, these abnormalities may be related to abnormal brain growth, maturation, and/or immune system dysregulation.