von Economo neurons in autism: A stereologic study of the frontoinsular cortex in children

Characterization of the of the Pathological and Biochemical Markers That Correlate to the Clinical Features of Autism. Subproject 2. Contribution of Significant Delay of Neuronal Development and Metabolic Shift of Neurons to Clinical Phenotype of Autism

“…Abnormal networking of Purkinje cells, granule neurons, and UBCs may contribute to altered cerebellar coordination of locomotion and motor learning and planning, as well as of higher cognitive processing [58]. Flocculonodular dysplasia appears to be another sign of the mosaic of local developmental defects, most likely predetermined by the spatial patterning of germinal zones in developing rhombic lip [110], and coexisting with more general developmental defects resulting in the accelerated growth of the brain in early childhood [89], minicolumn pathology [13,14], reduced neuron volume [7,108,111], and desynchronized neuronal growth in many brain regions [111] observed in autism.…”

“…Small sizes of neurons in autistic subjects have been reported in neuropathological evaluations without morphometric support [12,13,66,67], and in morphometric studies that estimate neuronal volume [64,108,119,130] or neuronal crosssectional areas [43]. A small size of neurons has been reported in 22-to 29-year-old autistic subjects in the hippocampus, amygdala, medial septal nucleus, cerebellar nuclei, and inferior olive [12,13,66,67].…”

“…Since then, implementation of broader diagnostic terms such as Autism Spectrum Disorder (ASD), examination of larger cohorts, applications of stereology, and functional and structural magnetic resonance imaging (MRI) have resulted in the detection of several major types of pathology, most likely contributing to the clinical phenotype. An emerging concept of autism-related brain pathology integrates evidence of (a) abnormal acceleration of brain growth in early childhood [89], (b) minicolumn pathology [13,14], (c) curtailed neuronal development [7,108] and brain structure-specific delays of neuronal growth [111] with indications of abnormalities in brain cytoarchitecture [4,7], metabolic modifications with abnormal amyloid protein precursor (APP) processing [5,101], enhanced oxidative stress [17] and enhanced turnover of cell organelles with pigment accumulation and glial activation [68].…”

“…Cholinergic neurons of the magnocellular basal complex modulate anxiety, arousal, and emotional and motor responses [68,93]. Although several postmortem morphometric studies have documented developmental alterations in the neocortex [62,64,108,119,130], cerebellum, and brainstem [73,74], the reported morphometric characteristics of the developmental alterations in subcortical structures are limited to the amygdala [113] and hippocampus [104]. Therefore, the first aim of this study was to test the hypothesis that developmental alterations of neuronal growth are part of a global encephalopathy of autism, including subcortical structures, hippocampus, archicortex, cerebellum, and brainstem.…”

“…The pathological acceleration of the growth of the brain regions involved in cognitive, social and emotional functions and in language development indicates that these disproportions contribute to the functional deficits observed in autism [23,24,31,55,121]. On the other hand, neocortical studies in autism have revealed a 67% increase in the number of neurons in the prefrontal cortex [34], a 53% increase in the ratio between von Economo neurons and pyramidal neurons in the fronto-insular cortex [108], but a reduced number of neurons in the fusiform gyrus [130]. These differences suggest regional disproportions and desynchronization of brain development in autism.…”