All subcortical arrangements are primarily nuclear in type. The cortex was the first part of the brain to evolve a radial and laminar arrangement of cells. The resultant modular arrangement is based on the cell minicolumn: a self-contained ecosystem of connectivity linking afferent, efferent and interneuronal connections. Our preliminary study of the fundamental processing unit of the cortex, the minicolumn, indicates that the modular neocortical organization in the brains of autistic individuals differs from that of controls. More specifically, a study of 3 neocortical sites in 9 autistic brains and an equal number of normal controls has shown significant differences in the horizontal spacing that separates minicolumns. It also revealed differences in their internal structure: less neuropil space in the periphery of the minicolumn and increased mean cell spacing. Similar abnormalities have now been reported in Asperger's syndrome but appear absent in Down syndrome (a control group added for mental retardation). This study will examine differences in minicolumnar morphometry between 24 autistic brains and 24 controls, matched for age and sex, from both the Autism Tissue Program and the Yakovlev-Haleem Collection (Armed Forces Institute of Pathology). The patients provide a new cohort not previously examined by the investigator. Ten Down syndrome brains will provide a second control group. Sampled cortical regions include Brodmann's areas 4, 9, 10, 17, 21, 22, 30, 33, and 39, which represent sensory, motor, association and limbic cortex obtained from 4 different brain lobes. The study will utilize quantified computer imaging and stereology in both Nissl and myelin-stained material. The parameters tested include the width of minicolumns, the amount of neuropil space within them, the mean cell density within each minicolumn, individual lamina depth, cell size and type (pyramidal versus non pyramidal), and the distribution of cell types among different lamina. The study will employ inter-myelinated bundle measurements as a way of corroborating our minicolumnar width parameters. We will compare the results within multiple regions of the cortex as well as for lateralization. Finally, we will correlate our minicolunmar parameters with different dimensions on the ADI. This study aims at better understanding the neuroanatomical basis of autism. If validated, positive results from our studies will yield a great understanding of autism. For example, many alleged animal models of autism lack the human neuroanatomic information to justify their utility. Candidate gene studies could also be refined if neuroanatomic development in autism was better understood. Treatment modalities, especially neuropharmaceutical agents, will prove more specific as their targets are better understood.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH069991-04
Application #
7237824
Study Section
Special Emphasis Panel (ZRG1-DBD (01))
Program Officer
Meinecke, Douglas L
Project Start
2004-07-01
Project End
2008-05-31
Budget Start
2007-06-01
Budget End
2008-05-31
Support Year
4
Fiscal Year
2007
Total Cost
$250,889
Indirect Cost
Name
University of Louisville
Department
Psychiatry
Type
Schools of Medicine
DUNS #
057588857
City
Louisville
State
KY
Country
United States
Zip Code
40292
Seelan, Ratnam S; Pisano, M Michele; Greene, Robert M et al. (2011) Differential methylation of the gene encoding myo-inositol 3-phosphate synthase (Isyna1) in rat tissues. Epigenomics 3:111-24
Baruth, Joshua M; Casanova, Manuel F; Sears, Lonnie et al. (2010) Early-stage visual processing abnormalities in high-functioning autism spectrum disorder (ASD). Transl Neurosci 1:177-187
Casanova, Manuel F; Trippe 2nd, Juan; Tillquist, Christopher R et al. (2010) Dolphin insula reflects minicolumnar organization of mammalian isocortex. Transl Neurosci 1:37-42
Casanova, Manuel F (2010) Cortical organization: a description and interpretation of anatomical findings based on systems theory. Transl Neurosci 1:62-71
Seelan, Ratnam S; Lakshmanan, Jaganathan; Casanova, Manuel F et al. (2009) Identification of myo-inositol-3-phosphate synthase isoforms: characterization, expression, and putative role of a 16-kDa gamma(c) isoform. J Biol Chem 284:9443-57
Casanova, Manuel F; Trippe 2nd, Juan; Tillquist, Christopher et al. (2009) Morphometric variability of minicolumns in the striate cortex of Homo sapiens, Macaca mulatta, and Pan troglodytes. J Anat 214:226-34
Casanova, Manuel F; Tillquist, Christopher R (2008) Encephalization, emergent properties, and psychiatry: a minicolumnar perspective. Neuroscientist 14:101-18
Seelan, R S; Khalyfa, A; Lakshmanan, J et al. (2008) Deciphering the lithium transcriptome: microarray profiling of lithium-modulated gene expression in human neuronal cells. Neuroscience 151:1184-97
Casanova, Manuel F (2008) The minicolumnopathy of autism: A link between migraine and gastrointestinal symptoms. Med Hypotheses 70:73-80
Casanova, Manuel F; Kreczmanski, Pawel; Trippe 2nd, Juan et al. (2008) Neuronal distribution in the neocortex of schizophrenic patients. Psychiatry Res 158:267-77

Showing the most recent 10 out of 18 publications