Ryan J. Dean

The corpus callosum is the largest commissure in the mammalian brain and plays a major role in supporting cognitive processes required for adapting to complex environments. Individuals born with Corpus Callosum Dysgenesis (CCD), characterized by malformations of the corpus callosum, commonly exhibit deficits in social navigation, abstract problem-solving, decision-making, and self-awareness. Metacognition is a key cognitive process that supports these functions; however, it has yet to be tested comprehensively in individuals with CCD. Over three experiments, and three CCD cohorts, we tested the impact of this neurodevelopmental disorder on perceptual accuracy, confidence judgements, and metacognitive efficiency using two variants of a Random Dot Kinematogram task within lab, online, and VR conditions. We found that individuals with CCD typically displayed normal perceptual accuracy but failed to adjust their confidence judgements in line with task difficulty. Computational modelling revealed that this difference was explained by lower metacognitive efficiency driven by consistently lower metacognitive sensitivity. Together, these results provide evidence that the corpus callosum plays a crucial role in supporting metacognition.

Corpus callosum dysgenesis is one of the most common congenital neurological malformations. Despite being a clear and identifiable structural alteration of the brain’s white matter connectivity, the impact of corpus callosum dysgenesis on cognition and behaviour has remained unclear. Here we build upon past clinical observations in the literature to define the clinical phenotype of corpus callosum dysgenesis better using unadjusted and adjusted group differences compared with a neurotypical sample on a range of social and cognitive measures that have been previously reported to be impacted by a corpus callosum dysgenesis diagnosis. Those with a diagnosis of corpus callosum dysgenesis ( n = 22) demonstrated significantly higher persuadability, credulity, and insensitivity to social trickery than neurotypical ( n = 86) participants, after controlling for age, sex, education, autistic-like traits, social intelligence, and general cognition. To explore this further, machine learning, utilising a set neurotypical sample for training the normative covariance structure of our psychometric variables, was used to test whether these dimensions possessed the capability to discriminate between a test-set of neurotypical and corpus callosum dysgenesis participants. We found that participants with a diagnosis of corpus callosum dysgenesis were best classed within dimension space along the same axis as persuadability, credulity, and insensitivity to social trickery after controlling for age and sex, with Leave-One-Out-Cross-Validation across 250 training-set permutations providing a mean accuracy of 71.7%. These results have wide- reaching implications for a) the characterisation of corpus callosum dysgenesis, and b) the role of the corpus callosum in social inference.

Corpus callosum dysgenesis (CCD) is a congenital disorder that incorporates either partial or complete absence of the largest cerebral commissure. Remodelling of the interhemispheric fissure (IHF) provides a substrate for callosal axons to cross between hemispheres, and its failure is the main cause of complete CCD. However, it is unclear whether defects in this process could give rise to the heterogeneity of expressivity and phenotypes seen in human cases of CCD. We identify incomplete IHF remodelling as the key structural correlate for the range of callosal abnormalities in inbred and outcrossed BTBR mouse strains, as well as in humans with partial CCD. We identify an eight base-pair deletion in Draxin and misregulated astroglial and leptomeningeal proliferation as genetic and cellular factors for variable IHF remodelling and CCD in BTBR strains. These findings support a model where genetic events determine corpus callosum structure by influencing leptomeningeal-astroglial interactions at the IHF.