Search

The anterior cingulate cortex, which is involved in cognitive and affective functioning, is important in investigating disorders in which individuals exhibit impairments in higher-order functions. In this study, we examined the anterior midcingulate cortex (aMCC) at the cellular level in patients with autism and in controls. We focused our analysis on layer V of the aMCC because it contains von Economo neurons, specialized cells thought to be involved in emotional expression and focused attention. Using a stereologic approach, we determined whether there were neuropathologic changes in von Economo neuron number, pyramidal neuron number, or pyramidal neuron size between diagnostic groups. When the groups were subdivided into young children and adolescents, pyramidal neuron and von Economo neuron numbers positively correlated with autism severity in young children, as measured by the Autism Diagnostic Interview-Revised. Young children with autism also had significantly smaller pyramidal neurons than their matched controls. Because the aMCC is involved in decision-making during uncertain situations, decreased pyramidal neuron size may reflect a potential reduction in the functional connectivity of the aMCC.

Autism is a neurodevelopmental disorder characterized by deficits in social interaction and social communication, as well as by the presence of repetitive and stereotyped behaviors and interests. Brodmann areas 44 and 45 in the inferior frontal cortex, which are involved in language processing, imitation function, and sociality processing networks, have been implicated in this complex disorder. Using a stereologic approach, this study aims to explore the presence of neuropathological differences in areas 44 and 45 in patients with autism compared to age- and hemisphere-matched controls. Based on previous evidence in the fusiform gyrus, we expected to find a decrease in the number and size of pyramidal neurons as well as an increase in volume of layers III, V, and VI in patients with autism. We observed significantly smaller pyramidal neurons in patients with autism compared to controls, although there was no difference in pyramidal neuron numbers or layer volumes. The reduced pyramidal neuron size suggests that a certain degree of dysfunction of areas 44 and 45 plays a role in the pathology of autism. Our results also support previous studies that have shown specific cellular neuropathology in autism with regionally specific reduction in neuron size, and provide further evidence for the possible involvement of the mirror neuron system, as well as impairment of neuronal networks relevant to communication and social behaviors, in this disorder.

The presence of von Economo neurons (VENs) in the frontoinsular cortex (FI) has been linked to a possible role in the integration of bodily feelings, emotional regulation, and goal-directed behaviors. They have also been implicated in fast intuitive evaluation of complex social situations. Several studies reported a decreased number of VENs in neuropsychiatric diseases in which the "embodied" dimension of social cognition is markedly affected. Neuropathological analyses of VENs in patients with autism are few and did not report alterations in VEN numbers. In this study we re-evaluated the possible presence of changes in VEN numbers and their relationship with the diagnosis of autism. Using a stereologic approach we quantified VENs and pyramidal neurons in layer V of FI in postmortem brains of four young patients with autism and three comparably aged controls. We also investigated possible autism-related differences in FI layer V volume. Patients with autism consistently had a significantly higher ratio of VENs to pyramidal neurons (p=0.020) than control subjects. This result may reflect the presence of neuronal overgrowth in young patients with autism and may also be related to alterations in migration, cortical lamination, and apoptosis. Higher numbers of VENs in the FI of patients with autism may also underlie a heightened interoception, described in some clinical observations., (Copyright © 2010 Elsevier B.V. All rights reserved.)