Minicolumnar abnormalities in autism
Abstract
Autism is characterized by qualitative abnormalities in behavior and higher order cognitive functions. Minicolumnar irregularities observed in autism provide a neurologically sound localization to observed clinical and anatomical abnormalities. This study corroborates the initial reports of a minicolumnopathy in autism within an independent sample. The patient population consisted of six age-matched pairs of patients (DSM-IV-TR and ADI-R diagnosed) and controls. Digital micrographs were taken from cortical areas S1, 4, 9, and 17. The image analysis produced estimates of minicolumnar width (CW), mean interneuronal distance, variability in CW (V (CW)), cross section of Nissl-stained somata, boundary length of stained somata per unit area, and the planar convexity. On average CW was 27.2 microm in controls and 25.7 microm in autistic patients (P = 0.0234). Mean neuron and nucleolar cross sections were found to be smaller in autistic cases compared to controls, while neuron density in autism exceeded the comparison group by 23%. Analysis of inter- and intracluster distances of a Delaunay triangulation suggests that the increased cell density is the result of a greater number of minicolumns, otherwise the number of cells per minicolumns appears normal. A reduction in both somatic and nucleolar cross sections could reflect a bias towards shorter connecting fibers, which favors local computation at the expense of inter-areal and callosal connectivity.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Our findings are not inconsistent with the mini-column hypothesis of autism.
“Our findings are not inconsistent with the mini-column hypothesis of autism 20 which postulates that symmetrical proliferation of periventricular progenitor cells leads to an increased number of mini-columns, which may have a role in the pathogenesis of SA hyper-expansion and later emergence of the disorder 18,21 .”
From Early brain development in infants at high risk for autism spectrum disorder (2017) · cites this paper as [20]
Cites
Receptive fields, binocular interaction and functional architecture in the cat’s visual cortex
Hubel, D. H., & Wiesel, T. N. (1962) · The Journal of Physiology · doi:10.1113/jphysiol.1962.sp006837 · Cited by 13,680 · see citing works
Lord, C., Rutter, M., & Le Couteur, A. (1994) · Journal of Autism and Developmental Disorders · doi:10.1007/bf02172145 · Cited by 9,065 · see citing works
Cortex: Statistics and Geometry of Neuronal Connectivity
Braitenberg, V., & Schüz, A. (1998) · doi:10.1007/978-3-662-03733-1 · Cited by 1,178 · cited 2× · see citing works
“Of the remaining objects, those with areas above the 15th percentile were used for minicolumn fragment detection, while the smaller objects were classified as interneurons based on the fraction of all neurons estimated to be inhibitory by Braitenberg and Schüz [12].”
BackgroundPetrides, M., & Pandya, D. N. (2002) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2001.02090.x · Cited by 882 · see citing works
Minicolumnar pathology in autism
Casanova, M. F., Buxhoeveden, D. P., Switala, A. E., & Roy, E. (2002) · Neurology · doi:10.1212/wnl.58.3.428 · Cited by 846 · see citing works
Self-citationDeFelipe, J. (1997) · Journal of Chemical Neuroanatomy · doi:10.1016/s0891-0618(97)10013-8 · Cited by 550 · see citing works
Lau, H. C., Rogers, R. D., Haggard, P., & Passingham, R. E. (2004) · Science · doi:10.1126/science.1090973 · Cited by 539 · see citing works
The brain response to personally familiar faces in autism: Findings of fusiform activity and beyond
Pierce, K. (2004) · Brain · doi:10.1093/brain/awh289 · Cited by 432 · see citing works
MAPS IN THE BRAIN: What Can We Learn from Them?
Chklovskii, D. B., & Koulakov, A. A. (2004) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.27.070203.144226 · Cited by 366 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Autism spectrum disorders: developmental disconnection syndromes
Geschwind, D. H., & Levitt, P. (2007) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2007.01.009 · Cited by 1,411 · see citing works
Robertson, C. E., & Baron-Cohen, S. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.112 · Cited by 1,157 · see citing works
Early brain development in infants at high risk for autism spectrum disorder
The IBIS Network, Hazlett, H. C., Gu, H., Munsell, B. C., Kim, S. H., Styner, M., Wolff, J. J., Elison, J. T., Swanson, M. R., Zhu, H., et al. (2017) · Nature · doi:10.1038/nature21369 · Cited by 1,128 · see citing works
Mapping early brain development in autism
Courchesne, E., Pierce, K., Schumann, C. M., Redcay, E., Buckwalter, J. A., Kennedy, D. P., & Morgan, J. (2007) · Neuron · doi:10.1016/j.neuron.2007.10.016 · Cited by 860 · see citing works
Advancing the understanding of autism disease mechanisms through genetics
de la Torre-Ubieta, L., Won, H., Stein, J. L., & Geschwind, D. H. (2016) · Nature Medicine · doi:10.1038/nm.4071 · Cited by 827 · see citing works
Neuron Number and Size in Prefrontal Cortex of Children With Autism
Courchesne, E., Mouton, P. R., Calhoun, M. E., Semendeferi, K., Ahrens-Barbeau, C., Hallet, M. J., Barnes, C. C., & Pierce, K. (2011) · JAMA · doi:10.1001/jama.2011.1638 · Cited by 779 · see citing works
The New Neurobiology of Autism: Cortex, Connectivity, and Neuronal Organization
Minshew, N. J., & Williams, D. L. (2007) · Archives of Neurology · doi:10.1001/archneur.64.7.945 · Cited by 592 · see citing works
Autism as a neural systems disorder: A theory of frontal-posterior underconnectivity
Just, M. A., Keller, T. A., Malave, V. L., Kana, R. K., & Varma, S. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2012.02.007 · Cited by 578 · see citing works
The neuropathology of autism: defects of neurogenesis and neuronal migration, and dysplastic changes
Wegiel, J., Kuchna, I., Nowicki, K., Imaki, H., Wegiel, J., Marchi, E., Ma, S. Y., Chauhan, A., Chauhan, V., Bobrowicz, T. W., et al. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0655-4 · Cited by 577 · see citing works
Altered neural connectivity in excitatory and inhibitory cortical circuits in autism
Zikopoulos, B., & Barbas, H. (2013) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2013.00609 · Cited by 313 · see citing works
Barttfeld, P., Wicker, B., Cukier, S., Navarta, S., Lew, S., & Sigman, M. (2011) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2010.11.024 · Cited by 311 · see citing works
The Emerging Picture of Autism Spectrum Disorder: Genetics and Pathology
Chen, J. A., Peñagarikano, O., Belgard, T. G., Swarup, V., & Geschwind, D. H. (2015) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-012414-040405 · Cited by 254 · see citing works
Neurons in the fusiform gyrus are fewer and smaller in autism
van Kooten, I. A. J., Palmen, S. J. M. C., von Cappeln, P., Steinbusch, H. W. M., Korr, H., Heinsen, H., Hof, P. R., van Engeland, H., & Schmitz, C. (2008) · Brain · doi:10.1093/brain/awn033 · Cited by 263 · see citing works
Self-citationDevelopmental Trajectories of Resting EEG Power: An Endophenotype of Autism Spectrum Disorder
Tierney, A. L., Gabard-Durnam, L., Vogel-Farley, V., Tager-Flusberg, H., & Nelson, C. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039127 · Cited by 226 · see citing works
Disruption of functional organization within the primary motor cortex in children with autism
Nebel, M. B., Joel, S. E., Muschelli, J., Barber, A. D., Caffo, B. S., Pekar, J. J., & Mostofsky, S. H. (2014) · Human Brain Mapping · doi:10.1002/hbm.22188 · Cited by 213 · see citing works
Decreased GABA <sub>B</sub> receptors in the cingulate cortex and fusiform gyrus in Autism
Oblak, A. L., Gibbs, T. T., & Blatt, G. J. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06858.x · Cited by 203 · see citing works
Spatial Organization of Neurons in the Frontal Pole Sets Humans Apart from Great Apes
Semendeferi, K., Teffer, K., Buxhoeveden, D. P., Park, M. S., Bludau, S., Amunts, K., Travis, K., & Buckwalter, J. (2011) · Cerebral Cortex · doi:10.1093/cercor/bhq191 · Cited by 210 · see citing works
Autism genetics: searching for specificity and convergence
Berg, J. M., & Geschwind, D. H. (2012) · Genome Biology · doi:10.1186/gb-2012-13-7-247 · Cited by 192 · see citing works
Stephenson, D. T., O'Neill, S. M., Narayan, S., Tiwari, A., Arnold, E., Samaroo, H. D., Du, F., Ring, R. H., Campbell, B., Pletcher, M., et al. (2011) · Molecular Autism · doi:10.1186/2040-2392-2-7 · Cited by 180 · see citing works
Izawa, J., Pekny, S. E., Marko, M. K., Haswell, C. C., Shadmehr, R., & Mostofsky, S. H. (2012) · Autism Research · doi:10.1002/aur.1222 · Cited by 182 · see citing works
White matter fractional anisotrophy differences and correlates of diagnostic symptoms in autism
Cheung, C., Chua, S. E., Cheung, V., Khong, P. L., Tai, K. S., Wong, T. K. W., Ho, T. P., & McAlonan, G. M. (2009) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2009.02086.x · Cited by 178 · see citing works
Focal cortical dysplasias in autism spectrum disorders
Casanova, M. F., El-Baz, A. S., Kamat, S. S., Dombroski, B. A., Khalifa, F., Elnakib, A., Soliman, A., Allison-McNutt, A., & Switala, A. E. (2013) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-1-67 · Cited by 150 · see citing works
Self-citationAutism: The first firm finding = underconnectivity?
Hughes, J. R. (2007) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2007.03.010 · Cited by 156 · see citing works
Fetit, R., Hillary, R. F., Price, D. J., & Lawrie, S. M. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.07.014 · Cited by 148 · see citing works
A Shift to Randomness of Brain Oscillations in People with Autism
Lai, M.-C., Lombardo, M. V., Chakrabarti, B., Sadek, S. A., Pasco, G., Wheelwright, S. J., Bullmore, E. T., Baron-Cohen, S., & Suckling, J. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.06.027 · Cited by 153 · see citing works
Blanquie, O., Yang, J.-W., Kilb, W., Sharopov, S., Sinning, A., & Luhmann, H. J. (2017) · eLife · doi:10.7554/elife.27696 · Cited by 114 · see citing works
Global motion perception deficits in autism are reflected as early as primary visual cortex
Robertson, C. E., Thomas, C., Kravitz, D. J., Wallace, G. L., Baron-Cohen, S., Martin, A., & Baker, C. I. (2014) · Brain · doi:10.1093/brain/awu189 · Cited by 122 · see citing works
Overproduction of Upper-Layer Neurons in the Neocortex Leads to Autism-like Features in Mice
Fang, W.-Q., Chen, W.-W., Jiang, L., Liu, K., Yung, W.-H., Fu, A. K. Y., & Ip, N. Y. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.11.003 · Cited by 114 · see citing works
Neuropil distribution in the cerebral cortex differs between humans and chimpanzees
Spocter, M. A., Hopkins, W. D., Barks, S. K., Bianchi, S., Hehmeyer, A. E., Anderson, S. M., Stimpson, C. D., Fobbs, A. J., Hof, P. R., & Sherwood, C. C. (2012) · Journal of Comparative Neurology · doi:10.1002/cne.23074 · Cited by 113 · see citing works
Self-citationRegional homogeneity of fMRI time series in autism spectrum disorders
Shukla, D. K., Keehn, B., & Müller, R. A. (2010) · Neuroscience Letters · doi:10.1016/j.neulet.2010.03.080 · Cited by 109 · see citing works
Immune system gene dysregulation in autism and schizophrenia
Michel, M., Schmidt, M. J., & Mirnics, K. (2012) · Developmental Neurobiology · doi:10.1002/dneu.22044 · Cited by 107 · see citing works
A neural substrate for atypical low-level visual processing in autism spectrum disorder
Vandenbroucke, M. W. G., Scholte, H. S., van Engeland, H., Lamme, V. A. F., & Kemner, C. (2008) · Brain · doi:10.1093/brain/awm321 · Cited by 107 · see citing works
Self-citationLibero, L. E., DeRamus, T. P., Deshpande, H. D., & Kana, R. K. (2014) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2014.07.001 · Cited by 95 · see citing works
Review: Cortical construction in autism spectrum disorder: columns, connectivity and the subplate
Hutsler, J. J., & Casanova, M. F. (2016) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12227 · Cited by 94 · see citing works
Self-citationPort, R. G., Gaetz, W., Bloy, L., Wang, D., Blaskey, L., Kuschner, E. S., Levy, S. E., Brodkin, E. S., & Roberts, T. P. L. (2017) · Autism Research · doi:10.1002/aur.1686 · Cited by 94 · see citing works
Casanova, M. F., El-Baz, A., Mott, M., Mannheim, G., Hassan, H., Fahmi, R., Giedd, J., Rumsey, J. M., Switala, A. E., & Farag, A. (2009) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-008-0681-4 · Cited by 90 · see citing works
Self-citationKemner, C., van Ewijk, L., van Engeland, H., & Hooge, I. (2008) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-007-0406-0 · Cited by 87 · see citing works
Autism spectrum disorder is associated with autonomic underarousal
BUJNAKOVA, I., ONDREJKA, I., MESTANIK, M., VISNOVCOVA, Z., MESTANIKOVA, A., HRTANEK, I., FLESKOVA, D., CALKOVSKA, A., & TONHAJZEROVA, I. (2016) · Physiological Research · doi:10.33549/physiolres.933528 · Cited by 75 · see citing works
Understanding autism and related disorders: What has imaging taught us?
Williams, D. L., & Minshew, N. J. (2007) · Neuroimaging Clinics of North America · doi:10.1016/j.nic.2007.07.007 · Cited by 71 · see citing works
Wegiel, J., Flory, M., Kuchna, I., Nowicki, K., Ma, S. Y., Imaki, H., Wegiel, J., Frackowiak, J., Kolecka, B. M., Wierzba-Bobrowicz, T., et al. (2015) · Acta Neuropathologica Communications · doi:10.1186/s40478-015-0183-5 · Cited by 47 · see citing works
Self-citationOpposite development of short- and long-range anterior cingulate pathways in autism
Zikopoulos, B., Liu, X., Tepe, J., Trutzer, I., John, Y. J., & Barbas, H. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1904-1 · Cited by 38 · see citing works
Neuron density is decreased in the prefrontal cortex in Williams syndrome
Lew, C. H., Brown, C., Bellugi, U., & Semendeferi, K. (2017) · Autism Research · doi:10.1002/aur.1677 · Cited by 18 · see citing works
- Authors
- Casanova, M. F., van Kooten, I. A. J., Switala, A. E., van Engeland, H., Heinsen, H., Steinbusch, H. W. M., Hof, P. R., Trippe, J., Stone, J., & Schmitz, C.
- Affiliations
- University of Louisville (US)
- University of Würzburg (DE)
- Maastricht University (NL)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Casanova, Manuel F.
- ORCID
- Venue
- Acta Neuropathologica
- Published
- 2006-07-04
- Volume
- 112
- Issue
- 3
- Pages
- 287-303
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- OpenAlex
- W2054390925
- Cited by
- 499
- References
- 9
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 14 · 2023: 15 · 2022: 15 · 2021: 18 · 2020: 22 · 2019: 20 · 2018: 24 · 2017: 31 · 2016: 41 · 2015: 43 · 2014: 29 · 2013: 48 · 2012: 36
- FWCI
- 11.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Autism Speaks (AS6288)
- National Institute of Mental Health (MH66392, R01MH062654, P50MH066392, R01MH061606, MH 61606, MH62654, R01MH069991, MH 69991)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Child Nutrition and Feeding Issues
- Keywords
- autism spectrum disorder, neuronal density, neuron size, cortical connectivity, local computation
- MeSH terms
- Adolescent, Adult, Algorithms, Autistic Disorder, Brain, Cell Count, Cell Nucleolus, Child, Child, Preschool, Female, Humans, Image Processing, Computer-Assisted, Interneurons, Male, Motor Cortex, Somatosensory Cortex, Tissue Fixation, Pyramidal Cells, Neocortex, Cell Size
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
