Neuronal Density and Architecture (Gray Level Index) in the Brains of Autistic Patients

Abstract

Although neuropathologic studies have centered on small samples, it is accepted that brains of autistic individuals tend to be large, on average. Knowledge regarding the cause of this macrocephaly is limited. Postmortem studies reveal little in terms of cortical dysplasia. Some of these studies suggest increased cell-packing density in subcortical structures. These neuronomorphometric studies have been subjective or based their conclusions on measures of neuronal density. Our study sought the possible presence of increased cell-packing density by using the Gray Level Index. The Gray Level Index is defined as the ratio of the area covered by Nissl-stained elements to unstained area in postmortem samples. Analyzed images included Brodmann's cortical areas 9, 21, and 22 of 9 autistic patients (7 males, 2 females; mean age of 12 years, with a range of 5 to 28 years) and 11 normal controls (7 males, 4 females; mean age of 14 years, with a range of 3 to 25 years). The overall multivariate test revealed significant differences both between autistic patients and controls (P = .001) and between hemispheres (P = .025). Follow-up univariate tests showed significant diagnosis-dependent effects in feature distance (P = .005), the standard deviation in distance (P = .016), and feature amplitude (P = .001). The overall mean Gray Level Index was 19.4% in controls and 18.7% in autism (P = .724). In autism, an increased number of minicolumns, combined with fewer cells per column (or their greater dispersion), results in no global difference in neuronal density.

Early Pharmacological Treatment of Autism: A Rationale for Developmental Treatment

“…Observations that require replication include reduced size and increased packing density of neurons in the limbic system, reduced dentritic trees in hippocampal neurons, apparently age-related changes in the diagonal band of Broca and the inferior olive, agenesis of the facial nucleus, and minicolumn pathology (Bauman and Kemper 1985) (Bauman and Kemper 1985;Casanova et al 2002a;Casanova et al 2002b;Kemper and Bauman 1993;Raymond et al 1996;Rodier et al 1996). There is more agreement about the presence of neocortical disorganization in a subset of cases, various olivary abnormalities in 2 studies (67% of cases) and decreased number and/or size of cerebellar Purkinje cells in 72% of cases (Arin et al 1991;Bailey et al 1998;Bauman and Kemper 1985;Casanova et al 2002a;Casanova et al 2002b;Casanova et al 2002c;Fatemi et al 2002a;Fehlow et al 1993;Guerin et al 1996;Ritvo et al 1986;Rodier et al 1996;Williams et al 1980). Reduction in the number of cerebellar Purkinje cells, coupled with relatively few abnormalities in the inferior olive, has been interpreted to imply that the initial brain changes in autism occur prior to birth (Bauman and Kemper 1985;Bauman and Kemper 2005).…”

Intrinsic gray-matter connectivity of the brain in adults with autism spectrum disorder

“…These gross-anatomical abnormalities are likely to reflect differences in the cytoarchitectonic make-up of individual brain regions in ASD, as can be observed in postmortem studies. For instance, individuals with ASD may have a reduced size, but increased number, of minicolumns (8), which could underpin differences in cortical surface area (9,10). Also, individuals with ASD may have an excess number of neurons in some brain regions (11), which in turn may affect measures of cortical thickness (9,12).…”

Beta-2-Microglobulin in Autism Spectrum Disorders

“…Subjects with ASD have abnormal brain circuitry, which may include high local synaptic connectivity and low long-range synaptic connectivity [39] . Abnormalities in synaptic and columnar structure, as well as increased [40][41][42][43][44] . In addition, children with ASD have been shown to have larger brain volumes than typically developing children [45] .…”