Corpus Callosum Disorders Research Program

The corpus callosum is the large bundle of fibers that typically connects the right and left halves of the brain.  It made of about 200 million nerve fibers.

‘Dysgenesis’ is the biological term for abnormal (dys) development (genesis). In individuals with dysgenesis of the corpus callosum (DCC), this bundle does not form normally.  It may be completely absent (agenesis), partially absent (partial agenesis), thin (hypoplasia) or malformed in some other manner.

Our studies of callosal dysgenesis are designed to help individuals with DCC and their families, while simultaneously enriching scientific knowledge about cerebral connectivity and providing insights about other conditions such as autism.

Left/top: diffusion tensor imaging for a typical brain. The large red area in the center is the corpus callosum.  Right/bottom: brain of an individual with agenesis of the corpus callosum.

Information about the cognitive, social and emotional consequences of DCC is very limited, leaving families to trial-and-error methods for helping their children with this condition. Our studies are designed to discover more about these areas of functioning in DCC, particularly the mechanisms that cause unusual thinking and behaviors. Clearer understanding of the brain mechanisms involved in DCC can direct refinement of treatment plans to maximize success for these individuals.

At the same time, individuals with DCC are very unique and can shed light onto various scientific questions such as: How does the brain adapt when major connections are malformed? How can we measure effective connectivity in the brain? What role does the corpus callosum play in a typical brain?

Finally, the clinical significance of studies on DCC extends beyond the disorder itself to other illnesses that are likely to arise from abnormal connectivity of the brain. It is likely that several psychiatric illnesses include such abnormal connectivity, yet very little is known about this at present. For instance, autism is thought to feature altered connectivity that arises from the altered brain development in this disorder. (Please see our AUTISM research for further details).

Longitudinal Study of Development in Infants and Toddlers with DCC

This online study is for parents of children with DCC who are younger than 5 years old.  ENROLL NOW!!

Our aim is to understand how the behavioral development of children with dysgenesis of the corpus callosum (DCC) is influenced by their unique neuroanatomic, genetic and medical traits.  Ultimately, this understanding can be used in creation of more effective intervention techniques and support for children and adults with DCC.

Click here to learn more about this study.

Structure and Function of Brains with DCC

The structural differences between normal and acallosal brains are striking and the ability of individuals with DCC to perform many tasks in the absence of a corpus callosum provides a fascinating model for long-range connectivity and plasticity in the human brain. To date, our studies have focused on characterizing the structure and functional organization of high functioning adults with complete or partial callosal agenesis (AgCC), a subtype of DCC. While this represents only a segment of the entire DCC population, by eliminating some potential confounds (e.g., variation in developmental stage and major neuropathology unrelated to callosal malformation) we can more effectively isolate the changes specifically related to callosal malformation.

We have conducted a series of functional MRI studies evaluating the relative involvement of brain regions during rest and during specific tasks. In adults with complete AgCC, we identified the same pattern of bilateral resting state networks as is commonly found in other adults (with a corpus callosum).  This indicates that the corpus callosum is not necessary for development of bilateral resting state networks, although it may be heavily involved in such networks when it is present.

We have also conducted studies localizing active brain regions during specific tasks. To date, research has interpreted the behavioral findings in AgCC with the assumption that the parts of the brain that are present are also functionally intact. Our studies were designed to evaluate that assumption and to characterize any unique patterns of brain activation in these participants. These studies are a critical component to deciphering the mechanisms that cause behavior problems and cognitive difficulties in DCC. It is possible to have similar behavior patterns but with unique causal mechanisms. Understanding the mechanisms involved will greatly enhance development of interventions.

Invertible matches between AgCC (left) and control group (right) independent component spatial maps (6 samples out of 17 total pairs).

Histological Study of Cellular Structure in Brains with DCC

One component of the neural network that supports social cognition which may be damaged in AgCC are the von Economo neurons, which are large spindle-shaped neurons localized to two brain regions that are known to be involved in social and emotional cognition: anterior cingulate cortex and fronto-insular cortex. von Economo neurons appear late in development (emerging mainly postnatally) and are a recent phylogenetic specialization, and as a consequence they may be particularly vulnerable to neuropoathologies. We examined the population of von Economo neurons in postmortem brain specimens from two adults with isolated callosal agenesis.  In the two control cases, the ratio of all neurons to von Economo neurons was approximately 100:1. In the partial AgCC case, the ratio increased to approximately 200:1, while in the complete AgCC case the ratio reached approximately 1,000:1. These results indicate that von Economo neurons are selectively vulnerable in AgCC. Additionally, complete AgCC appears to be more detrimental to the von Economo neuron population than partial AgCC, suggesting that even a limited corpus callosum may provide a sustaining connection for the von Economo neuron population.


Eye-tracking and psychophysiological studies are designed to provide insight into how individuals with AgCC experience the world that they see. Eye-tracking involves monitoring where one’s eyes are looking. Research has shown that individuals with autism do not look at faces in a normal way: they spend much more time looking at the mouth than the eyes. This pattern is similar in AgCC, they also do not look at the eyes as much as controls do and are much poorer than controls at naming emotions, specifically anger and fear. Moreover, impairments in emotion naming were directly associated with an abnormal pattern of facial scanning.

AgCC subjects performed less accurately than controls in naming the emotion. Figure above: fixation density maps are shown for an AgCC subject (left/top) and a normal control (right/bottom), red indicates greatest number of fixations, plum the least.


We recorded psychophysiological measurements (galvanic skin response, heart rate, and respiration rate) from individuals with AgCC and control participants while they looked at an emotionally intense social scenes (pleasant, aversive, and neutral). Participants were asked to rate each image on a scale from negative to positive and on a scale of emotional intensity. Psychophysiological measures are a physical representation of the participant’s emotional arousal, while ratings reflect their cognitive judgment.

Below: Compared to healthy controls, ratings given by adults with AgCC had a compressed range and poor discrimination for both valence (positive vs. negative, Figure A) and arousal (intensity, Figure B). This pattern was most marked for negative pictures, which the AgCC group on average rated as more neutral and less intense than did controls.

Below:  Despite their impaired cognitive ratings of arousal, some subjects with AgCC showed large skin-conductance responses, and in general skin-conductance responses discriminated emotion categories and correlated with stimulus arousal ratings (C). In sum, while physiological arousal may be intact, individuals with AgCC give less emotionally intense ratings than controls.


Badaruddin, D. H., Andrews, G. L,. Bolte, S., Schilmoeller, K. J., Schilmoeller, G., Paul, L. K., & Brown, W. S. (2007). Social and behavioral problems of children with agenesis of the corpus callosum. Child Psychiatry Hum Dev, 38(4), 287-302.

Brown WS, Anderson LB, Symington MF, Paul LK. (2012). Decision-making in individuals with agenesis of the corpus callosum: expectancy-valence in the Iowa Gambling Task. Arch Clin Neuropsychol. 2012 Aug;27(5):532-44.

Bridgman, M. W., Brown, W. S., Spezio, M. L., Leonard, M. K., Adolphs, R., & Paul, L. K. (2014). Facial emotion recognition in agenesis of the corpus callosum. Journal of Neurodevelopmental Disorders, 6(32). doi: 10.1186/1866-1955-6-32

Brown WS, Paul LK. (2000). Cognitive and psychosocial deficits in agenesis of the corpus callosum. Cognitive neuropsychiatry. 2000; 5:135 – 157.

Brown, W. S., Paul, L. K., Symington, M., & Dietrich, R. (2005). Comprehension of humor in primary agenesis of the corpus callosum. Neuropsychologia, 43(6), 906-916.

Brown, W. S., Symingtion, M., VanLancker-Sidtis, D., Dietrich, R., & Paul, L. K. (2005). Paralinguistic processing in children with callosal agenesis: emergence of neurolinguistic deficits. Brain and Language, 93(2), 135-139.

Brown, W. S., Thrasher, E. D., & Paul, L. K. (2001). Interhemispheric Stroop effects in partial and complete agenesis of the corpus callosum. Journal of the International Neuropsychological Society, 7(3), 302-311.

Demopoulos C, Yu N, Paul LK, Sherr EH, Marco EJ. (2015). Corpus callosum in cognitive and sensory processing: insights into autism. Future neurology. 2015; 10(2):147 – 160.

Erickson RL, Paul LK, Brown WS. (2014). Verbal learning and memory in agenesis of the corpus callosum. Neuropsychologia. 2014 Jul;60:121-30. PubMed PMID: 24933663.

Hines, R. J., Paul, L. K., Brown, W. S. (2002). Spatial attention in agenesis of the corpus callosum: shifting attention between visual fields. Neuropsychologia, 40(11), 1804-1814.

Hinkley LB, Marco EJ, Findlay AM, Honma S, Jeremy RJ, et al. (2012). The role of corpus callosum development in functional connectivity and cognitive processing. PLoS One. 2012;7(8):e39804. PubMed PMID: 22870191; PubMed Central PMCID: PMC3411722.

Kaufman, J.A., Paul, L.K., Manaye, K.F., Granstedt, A.E., Hof, P.R., Hakeem, A.Y. and Allman, J.M. (2008). Selective reduction of Von Economo neuron number in agenesis of the corpus callosum. Acta Neuropathologica, 116 (5), 479-489. ISSN 0001-6322.

Marco EJ, Harrell KM, Brown WS, Hill SS, Jeremy RJ, et al. (2012). Processing speed delays contribute to executive function deficits in individuals with agenesis of the corpus callosum. J Int Neuropsychol Soc. 2012 May;18(3):521-9. PubMed PMID: 22390821; PubMed Central PMCID: PMC3605885.

Mueller KL, Marion SD, Paul LK, Brown WS. (2009). Bimanual motor coordination in agenesis of the corpus callosum. Behav Neurosci. 2009 Oct;123(5):1000-11. PubMed PMID: 19824766.

Paul, L. K. (2011). Developmental malformation of the corpus callosum: a review of typical callosal development and examples of developmental disorders with callosal involvement. Journal of Neurodevelopmental Disorders, 3, 3-27.

Paul, L. K., Brown, W. S., Adolphs, R., Tyszka, J. M., Richards, L. J., Mukherjee, P., & Sherr, E. H. (2007). Agenesis of the corpus callosum: genetic, developmental and functional aspects of connectivity. Nature Reviews Neuroscience, 8(4), 287-299. doi: 10.1038/nrn2107

Paul, L. K., Corsello, C., Kennedy, D. P., & Adolphs, R. (2014). Agenesis of the corpus callosum and autism: a comprehensive comparison. Brain, 137, 1813-1829. doi: 10.1093/brain/awu070

Paul, L.K., Erickson, R.L., Hartman, J.A. & Brown, W.S. (2016). Learning and memory in individuals with agenesis of the corpus callosum. Neuropsychologia, 86, 183-192. doi:10.1016/j.neuropsychologia.2016.04.013.

Paul, L. K., Lautzenhiser, A., Brown, W. S., Hart, A., Neumann, D., Spezio, M., & Adolphs, R. (2006). Emotional arousal in agenesis of the corpus callosum. International Journal of Psychophysiology, 61(1), 47-56. doi: 10.1016/j.ijpsycho.2005.10.017

Paul, L. K., Schieffer, B., Brown, W. S. (2004). Social processing deficits in agenesis of the corpus callosum: narratives from the Thematic Appreciation Test. Archives of Clinical Neuropsychology, 19(2), 215-225.

Paul, L.K. & Tyszka, J.M. (2012). How important is the corpus callosum in resting-state networks? Future Neurology, 7(3), 231-234. doi:10.2217/fnl.12.17

Paul, L. K., Van Lancker-Sidtis, D., Schieffer, B., Dietrich, R., Brown, W. S. (2003). Communicative deficits in agenesis of the corpus callosum: nonliteral language and affective prosody. Brain and Language, 85(2), 313-324.

Rehmel JL, Brown WS, Paul LK. (in press). Proverb Comprehension in Individuals with Agenesis of the Corpus Callosum. Brain and Language.

Symington, S. H., Paul, L. K., Symington, M. F., Ono, M., & Brown, W. S. (2010). Social cognition in individuals with agenesis of the corpus callosum. Social Neuroscience, 5(3), 296-308.

Turk, A. A., Brown, W. S., Symington, M., & Paul, L. K. (2010). Social narratives in agenesis of the corpus callosum: linguistic analysis of the Thematic Apperception Test. Neuropsychologia, 48(1), 43-50.

Tyszka, J. M., Kennedy, D. P., Adolphs, R., & Paul, L. K. (2011). Intact bilateral resting-state networks in the absence of the corpus callosum. Journal of Neuroscience, 31(42), 15154-15162. doi: 10.1523/jneurosci.1453-11.2011