Corpus Callosum Volume and Neurocognition in Autism

  • Christopher J. Keary
  • Nancy J. Minshew
  • Rahul Bansal
  • Dhruman Goradia
  • Serguei Fedorov
  • Matcheri S. Keshavan
  • Antonio Y. HardanEmail author
Original Paper


The corpus callosum has recently been considered as an index of interhemispheric connectivity. This study applied a novel volumetric method to examine the size of the corpus callosum in 32 individuals with autism and 34 age-, gender- and IQ-matched controls and to investigate the relationship between this structure and cognitive measures linked to interhemispheric functioning. Participants with autism displayed reductions in total corpus callosum volume and in several of its subdivisions. Relationships were also observed between volumetric alterations and performance on several cognitive tests including the Tower of Hanoi test. These findings provide further evidence for anatomical alterations in the corpus callosum in autism, but warrant additional studies examining the relationship of this structure and specific measures of interhemispheric connectivity.


Autism Corpus callosum Volume MRI Connectivity Neuropsychological tests 



This work was supported in part by NIMH grant MH 64027 to Dr. Hardan, and NICHD grant HD 35469, and NICHD grant HD 35469 to Dr. Minshew. The authors thank Diane L Williams, PhD, for assistance in study design. The efforts and commitment of the participants and their families in this study are gratefully acknowledged.


  1. Alexander, A. L., Lee, J. E., Lazar, M., Boudos, R., DuBray, M. B., Oakes, T. R., et al. (2007). Diffusion tensor imaging of the corpus callosum in autism. NeuroImage, 34, 61–73. doi: 10.1016/j.neuroimage.2006.08.032.PubMedCrossRefGoogle Scholar
  2. Barnea-Goraly, N., Kwon, H., Menon, V., Eliez, S., Lotspeich, L., & Reiss, A. L. (2004). White matter structure in autism: Preliminary evidence from diffusion tensor imaging. Biological Psychiatry, 55, 323–326. doi: 10.1016/j.biopsych.2003.10.022.PubMedCrossRefGoogle Scholar
  3. Benjamini, Y., & Hochberg, T. (1995). Controlling the false discovery rate: A practical and powerful approach to multiple testing. Journal of the Royal Statistical Society. Series A (General), 85, 289–300.Google Scholar
  4. Benjamini, Y., & Hochberg, T. (2000). On the adaptive control of the false discovery rate in multiple testing with independent statistics. Journal of Educational and Behavioral Statistics, 26, 60–83.Google Scholar
  5. Brambilla, P., Hardan, A. Y., di Nemi, S. U., Perez, J., Soares, J. C., & Barale, F. (2003). Brain anatomy and development in autism: Review of structural MRI studies. Brain Research Bulletin, 61, 557–569. doi: 10.1016/j.brainresbull.2003.06.001.PubMedCrossRefGoogle Scholar
  6. Brown, W. S. (2003). Clinical neuropsychological assessment of callosal dysfunction: Multiple sclerosis and dyslexia. In E. Zaidel & M. Iacoboni (Eds.), The parallel brain: The cognitive neuroscience of the corpus callosum (pp. 391–406). Cambridge, MA: The MIT Press.Google Scholar
  7. Carper, R. A., & Courchesne, E. (2005). Localized enlargement of the frontal cortex in early autism. Biological Psychiatry, 57, 126–133. doi: 10.1016/j.biopsych.2004.11.005.PubMedCrossRefGoogle Scholar
  8. Casanova, M. F., Buxhoeveden, D. P., Switala, A. E., & Roy, E. (2002). Minicolumnar pathology in autism. Neurology, 58, 428–432.PubMedGoogle Scholar
  9. Casanova, M. F., van Kooten, I. A., Switala, A. E., van Engeland, H., Heinsen, H., Steinbusch, H. W., et al. (2006). Minicolumnar abnormalities in autism. Acta Neuropathologica, 112, 287–303. doi: 10.1007/s00401-006-0085-5.PubMedCrossRefGoogle Scholar
  10. D’Angelo, V., Napolitano, M., Gorgoglione, L., Scarabino, T., Latino, R., Simone, P., et al. (1997). Surgical treatment of anterior callosal tumors. Journal of Neurosurgical Sciences, 41, 117–122.PubMedGoogle Scholar
  11. Egaas, B., Courchesne, E., & Saitoh, O. (1995). Reduced size of corpus callosum in autism. Archives of Neurology, 52, 794–801.PubMedGoogle Scholar
  12. Feise, R. J. (2002). Do multiple outcome measures require p-value adjustment? BMC Medical Research Methodology, 2, 8. doi: 10.1186/1471-2288-2-8.PubMedCrossRefGoogle Scholar
  13. Frith, C. D., & Frith, U. (2006). The neural basis of mentalizing. Neuron, 18, 531–534. doi: 10.1016/j.neuron.2006.05.001.CrossRefGoogle Scholar
  14. Hardan, A. Y., Minshew, N. J., & Keshavan, M. S. (2000). Corpus callosum size in autism. Neurology, 55, 1033–1036.PubMedGoogle Scholar
  15. Hardan, A. Y., Kilpatrick, M., Keshavan, M. S., & Minshew, N. J. (2003). Motor performance and anatomic magnetic resonance imaging (MRI) of the basal ganglia in autism. Journal of Child Neurology, 18, 317–324. doi: 10.1177/08830738030180050801.PubMedCrossRefGoogle Scholar
  16. Herbert, M. R., Ziegler, D. A., Makris, N., Filipek, P. A., Kemper, T. L., Normandin, L. L., et al. (2004). Localization of white matter volume increase in autism and developmental language disorder. Annals of Neurology, 55, 530–540. doi: 10.1002/ana.20032.PubMedCrossRefGoogle Scholar
  17. Hollingshead, A. B. (1975). Four factor index of social status. New Haven, CT: Yale University Department of Sociology.Google Scholar
  18. Hughes, C., Russell, J., & Robbins, T. W. (1994). Evidence for executive dysfunction in autism. Neuropsychologia, 32, 477–492. doi: 10.1016/0028-3932(94)90092-2.PubMedCrossRefGoogle Scholar
  19. Just, M. A., Cherkassky, V. L., Keller, T. A., & Minshew, N. J. (2004). Cortical activation and synchronization during sentence comprehension in high-functioning autism: Evidence of underconnectivity. Brain, 127, 1811–1821. doi: 10.1093/brain/awh199.PubMedCrossRefGoogle Scholar
  20. Just, M. A., Cherkassky, V. L., Keller, T. A., Kana, R. K., & Minshew, N. J. (2007). Functional and anatomical cortical underconnectivity in autism: Evidence from an fMRI study of an executive function task and corpus callosum morphometry. Cerebral Cortex (New York, NY), 17, 951–961. doi: 10.1093/cercor/bhl006.CrossRefGoogle Scholar
  21. Kana, R. K., Keller, T. A., Cherkassky, V. L., Minshew, N. J., & Just, M. A. (2006). Sentence comprehension in autism: Thinking in pictures with decreased functional connectivity. Brain, 129, 2484–2493. doi: 10.1093/brain/awl164.PubMedCrossRefGoogle Scholar
  22. LeCouteur, A., Rutter, M., Lord, C., Rios, P., Robertson, S., Holdgrafer, M., et al. (1989). Autism diagnostic interview: A standardized investigator-based instrument. Journal of Autism and Developmental Disorders, 19, 363–387. doi: 10.1007/BF02212936.CrossRefGoogle Scholar
  23. Lord, C., Rutter, M., & LeCouteur, A. (1994). Autism diagnostic interview-revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. Journal of Autism and Developmental Disorders, 24, 659–685. doi: 10.1007/BF02172145.PubMedCrossRefGoogle Scholar
  24. Madden, D. J., Whiting, W. L., Huettel, S. A., White, L. E., MacFall, J. R., & Provenzale, J. M. (2004). Diffusion tensor imaging of adult age differences in cerebral white matter: Relation to response time. NeuroImage, 21, 1174–1181. doi: 10.1016/j.neuroimage.2003.11.004.PubMedCrossRefGoogle Scholar
  25. Magnotta, V. A., Harris, G., Andreasen, N. C., O’Leary, D. S., Yuh, W. T., & Heckel, D. (2002). Structural MR image processing using the BRAINS2 toolbox. Computerized Medical Imaging and Graphics, 26, 251–264. doi: 10.1016/S0895-6111(02)00011-3.PubMedCrossRefGoogle Scholar
  26. Manes, F., Piven, J., Vrancic, D., Nanclares, V., Plebst, C., & Starkstein, S. E. (1999). An MRI study of the corpus callosum and cerebellum in mentally retarded autistic individuals. The Journal of Neuropsychiatry and Clinical Neurosciences, 11, 470–474.PubMedGoogle Scholar
  27. Minshew, N. J., Goldstein, G., & Siegel, D. J. (1997). Neuropsychologic functioning in autism: Profile of a complex information processing disorder. Journal of the International Neuropsychological Society, 3, 303–316.PubMedGoogle Scholar
  28. Minshew, N. J., Meyer, J., & Goldstein, G. (2002). Abstract reasoning in autism: A dissociation between concept formation and concept identification. Neuropsychology, 16, 327–334. doi: 10.1037/0894-4105.16.3.327.PubMedCrossRefGoogle Scholar
  29. Muller-Oehring, E. M., Schulte, T., Raassi, C., Pfefferbaum, A., & Sullivan, E. V. (2007). Local-global interference is modulated by age, sex and anterior corpus callosum size. Brain Research, 1142, 189–205. doi: 10.1016/j.brainres.2007.01.062.PubMedCrossRefGoogle Scholar
  30. Newman, S. D., Capenter, P. A., Varma, S., & Just, M. A. (2003). Frontal and parietal participation in problem solving in the Tower of London: fMRI and computational modeling of planning and high-level perception. Neuropsychologia, 41, 1668–1682. doi: 10.1016/S0028-3932(03)00091-5.PubMedCrossRefGoogle Scholar
  31. Nyden, A., Carlsson, M., Carlsson, A., & Gillberg, C. (2004). Interhemispheric transfer in high-functioning children and adolescents with autism spectrum disorders: A controlled pilot study. Developmental Medicine and Child Neurology, 46, 448–454. doi: 10.1017/S001216220400074X.PubMedCrossRefGoogle Scholar
  32. Ozonoff, S., Pennington, B. F., & Rogers, S. J. (1991). Executive function deficits in high-functioning autistic individuals: Relationship to theory of mind. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 32, 1081–1105. doi: 10.1111/j.1469-7610.1991.tb00351.x.PubMedCrossRefGoogle Scholar
  33. Pandya, D. N., & Seltzer, B. (1986). The topography of commissioned fibers. In F. Lepore, M. Ptito, & H. H. Jasper (Eds.), Two hemispheres—one brain: Functions of the corpus callosum (pp. 44–73). New York: Liss.Google Scholar
  34. Paul, L. K., Brown, W. S., Adolphs, R., Tyszka, J. M., Richards, L. J., Mukherjee, P., et al. (2007). Agenesis of the corpus callosum: Genetic, developmental and functional aspects of connectivity. Nature Reviews. Neuroscience, 8, 287–299. doi: 10.1038/nrn2107.PubMedCrossRefGoogle Scholar
  35. Piven, J., Bailey, J., Ranson, B. J., & Arndt, S. (1997). An MRI study of the corpus callosum in autism. The American Journal of Psychiatry, 154, 1051–1056.PubMedGoogle Scholar
  36. Pozzilli, C., Bastianello, S., Padovani, A., Passafiume, D., Millefiorini, E., Bozzao, L., et al. (1991). Anterior corpus callosum atrophy and verbal fluency in multiple sclerosis. Cortex, 27, 441–445.PubMedGoogle Scholar
  37. Quigley, M., Cordes, D., Turski, P., Moritz, C., Haughton, V., Seth, R., et al. (2003). Role of the corpus callosum in functional connectivity. AJNR. American Journal of Neuroradiology, 24, 208–212.PubMedGoogle Scholar
  38. Quinn, K., & Geffen, G. (1986). The development of tactile transfer of information. Neuropsychologia, 24, 793–804. doi: 10.1016/0028-3932(86)90078-3.PubMedCrossRefGoogle Scholar
  39. Sánchez, M. M., Hearn, E. F., Do, D., Rilling, J. K., & Herndon, J. G. (1998). Differential rearing affects corpus callosum size and cognitive function of rhesus monkeys. Brain Research, 812, 38–49. doi: 10.1016/S0006-8993(98)00857-9.PubMedCrossRefGoogle Scholar
  40. Smith, A. B., Taylor, E., Brammer, M., & Rubia, K. (2004). Neural correlates of switching set as measured in fast, event-related functional magnetic resonance imaging. Human Brain Mapping, 21, 247–256. doi: 10.1002/hbm.20007.PubMedCrossRefGoogle Scholar
  41. Tárnok, Z., Barsi, P., Gádoros, J., & Halász, P. (2006). Executive dysfunction in frontal lesions and frontal epilepsy. Ideggyogyaszati Szemle, 20, 269–280.Google Scholar
  42. Thompson, L. L., & Parsons, O. A. (1985). Contribution of the TPT to adult neuropsychological assessment: A review. Journal of Clinical and Experimental Neuropsychology, 7, 430–444. doi: 10.1080/01688638508401275.PubMedCrossRefGoogle Scholar
  43. Vidal, C. N., Nicholsen, R., DeVito, T. J., Hayashi, K. M., Geaga, J. A., Drost, D. J., et al. (2006). Mapping corpus callosum deficits in autism: An index of aberrant cortical connectivity. Biological Psychiatry, 60, 218–225. doi: 10.1016/j.biopsych.2005.11.011.PubMedCrossRefGoogle Scholar
  44. Witelson, S. F. (1989). Hand and sex differences in the isthmus and genu of the human corpus callosum: A postmortem morphological study. Brain, 112, 799–835. doi: 10.1093/brain/112.3.799.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Christopher J. Keary
    • 1
  • Nancy J. Minshew
    • 1
  • Rahul Bansal
    • 2
  • Dhruman Goradia
    • 2
  • Serguei Fedorov
    • 2
  • Matcheri S. Keshavan
    • 3
  • Antonio Y. Hardan
    • 4
    Email author
  1. 1.Western Psychiatric Institute and ClinicUniversity of Pittsburgh School of MedicinePittsburghUSA
  2. 2.Department of PsychiatryWayne State UniversityDetroitUSA
  3. 3.Department of PsychiatryBeth Israel and Deaconess Medical Center, Harvard Medical SchoolBostonUSA
  4. 4.Department of Psychiatry and Behavioral SciencesStanford UniversityStanfordUSA

Personalised recommendations