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Von Economo neurons (VENs) and fork cells are principally located in the anterior cingulate cortex (ACC) and the frontoinsular cortex (FI). Both of these regions integrate inputs from the autonomic nervous system (ANS) and are involved in decision-making and perception of the emotional states of self and others. Familial dysautonomia (FD) is an orphan disorder characterized by autonomic dysfunction and behavioral abnormalities including repetitive behavior and emotional rigidity, which are also seen in autism spectrum disorder. To understand a possible link between the ANS and the cortical regions implicated in emotion regulation we studied VENs and fork cells in an autonomic disorder. We determined the densities of VENs, fork cells, and pyramidal neurons and the ratio of VENs and fork cells to pyramidal neurons in ACC and FI in 4 FD patient and 6 matched control brains using a stereologic approach. We identified alterations in densities of VENs and pyramidal neurons and their distributions in the ACC and FI in FD brains. These data suggest that alterations in migration and numbers of VENs may be involved in FD pathophysiology thereby supporting the notion of a functional link between VENs, the ANS and the peripheral nervous system in general.

There is growing clinical and neuropathologic evidence suggesting that cognitive decline in early Alzheimer’s disease (AD) is aggravated by a synergistic relationship between AD and cerebrovascular disease associated with cardiovascular risk factors such as diabetes and hypertension. Here we used the stereologic “Space Balls” method to investigate the relationships between AD pathology and cardiovascular risk factors in postmortem human brains of patients with hypertension and diabetes in two groups — one consisting of cases with AD diagnosis and one of cases without. Hippocampal CA1 and CA3 microvasculature length density estimates were generated to characterize quantitatively the contribution of cardiovascular risk factors to the severity of neuropathologic changes. Our main finding is that the mean and variance of length density values in the AD group were significantly increased from the non-AD group, regardless of the absence or presence of a cardiovascular risk factor. An additional finding is that in the AD group without a risk factor, dementia severity correlated with amount of length density change in the CA1 field—this correlation did not exist in the AD groups with risk factors. Our findings suggest a role for cardiovascular risk factors in quantifiable change of hippocampal CA1 field microvasculature, as well as suggest a possible role of cardiovascular risk factors in altering microvasculature pathology in the presence of AD.

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.