Increased persuadability and credulity in people with corpus callosum dysgenesis.

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, we examined the covariance structure of our psychometric variables using a machine learning algorithm trained on a neurotypical dataset. The algorithm was then used to test whether these dimensions possessed the capability to discriminate between a test-set of neurotypical and corpus callosum dysgenesis participants. After controlling for age and sex, and with Leave-One-Out-Cross-Validation across 250 training-set bootstrapped iterations, 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, with a mean accuracy of 71.7%. These results have implications for a) the characterisation of corpus callosum dysgenesis, and b) the role of the corpus callosum in social inference.

DRAXIN regulates interhemispheric fissure remodelling to influence the extent of corpus callosum formation.

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.

Verbal Adynamia and Conceptualization in Partial Rhombencephalosynapsis and Corpus Callosum Dysgenesis.

Verbal adynamia is characterized by markedly reduced spontaneous speech that is not attributable to a core language deficit such as impaired naming, reading, repetition, or comprehension. In some cases, verbal adynamia is severe enough to be considered dynamic aphasia. We report the case of a 40-year-old, left-handed, male native English speaker who presented with partial rhombencephalosynapsis, corpus callosum dysgenesis, and a language profile that is consistent with verbal adynamia, or subclinical dynamic aphasia, possibly underpinned by difficulties selecting and generating ideas for expression. This case is only the second investigation of dynamic aphasia in an individual with a congenital brain malformation. It is also the first detailed neuropsychological report of an adult with partial rhombencephalosynapsis and corpus callosum dysgenesis, and the only known case of superior intellectual abilities in this context.

Altered structural connectivity networks in a mouse model of complete and partial dysgenesis of the corpus callosum.

Corpus callosum dysgenesis (CCD) describes a collection of brain malformations in which the main fiber tract connecting the two hemispheres is either absent (complete CCD, or 'agenesis of the corpus callosum') or reduced in size (partial CCD). Humans with these neurodevelopmental disorders have a wide range of cognitive outcomes, including seemingly preserved features of interhemispheric communication in some cases. However, the structural substrates that could underlie this variability in outcome remain to be fully elucidated. Here, for the first time, we characterize the global brain connectivity of a mouse model of complete and partial CCD. We demonstrate features of structural brain connectivity that model those predicted in humans with CCD, including Probst bundles in complete CCD and heterotopic sigmoidal connections in partial CCD. Crucially, we also histologically validate the recently predicted ectopic sigmoid bundle present in humans with partial CCD, validating the utility of this mouse model for fine anatomical studies of this disorder. Taken together, this work describes a mouse model of altered structural connectivity in variable severity CCD and forms a foundation for future studies investigating the function and mechanisms of development of plastic tracts in developmental disorders of brain connectivity.

Increased cognitive complexity reveals abnormal brain network activity in individuals with corpus callosum dysgenesis.

Cognitive reasoning is thought to require functional interactions between whole-brain networks. Such networks rely on both cerebral hemispheres, with the corpus callosum providing cross-hemispheric communication. Here we used high-field functional magnetic resonance imaging (7 T fMRI), a well validated cognitive task, and brain network analyses to investigate the functional networks underlying cognitive reasoning in individuals with corpus callosum dysgenesis (CCD), an anatomical abnormality that affects the corpus callosum. Participants with CCD were asked to solve cognitive reasoning problems while their brain activity was measured using fMRI. The complexity of these problems was parametrically varied by changing the complexity of relations that needed to be established between shapes within each problem matrix. Behaviorally, participants showed a typical reduction in task performance as problem complexity increased. Task-evoked neural activity was observed in brain regions known to constitute two key cognitive control systems: the fronto-parietal and cingulo-opercular networks. Under low complexity demands, network topology and the patterns of local neural activity in the CCD group closely resembled those observed in neurotypical controls. By contrast, when asked to solve more complex problems, participants with CCD showed a reduction in neural activity and connectivity within the fronto-parietal network. These complexity-induced, as opposed to resting-state, differences in functional network activity help resolve the apparent paradox between preserved network architecture found at rest in CCD individuals, and the heterogeneous deficits they display in response to cognitive task demands [preprint: https://doi.org/10.1101/312629].

NFIB Haploinsufficiency Is Associated with Intellectual Disability and Macrocephaly.

The nuclear factor I (NFI) family of transcription factors play an important role in normal development of multiple organs. Three NFI family members are highly expressed in the brain, and deletions or sequence variants in two of these, NFIA and NFIX, have been associated with intellectual disability (ID) and brain malformations. NFIB, however, has not previously been implicated in human disease. Here, we present a cohort of 18 individuals with mild ID and behavioral issues who are haploinsufficient for NFIB. Ten individuals harbored overlapping microdeletions of the chromosomal 9p23-p22.2 region, ranging in size from 225 kb to 4.3 Mb. Five additional subjects had point sequence variations creating a premature termination codon, and three subjects harbored single-nucleotide variations resulting in an inactive protein as determined using an in vitro reporter assay. All individuals presented with additional variable neurodevelopmental phenotypes, including muscular hypotonia, motor and speech delay, attention deficit disorder, autism spectrum disorder, and behavioral abnormalities. While structural brain anomalies, including dysgenesis of corpus callosum, were variable, individuals most frequently presented with macrocephaly. To determine whether macrocephaly could be a functional consequence of NFIB disruption, we analyzed a cortex-specific Nfib conditional knockout mouse model, which is postnatally viable. Utilizing magnetic resonance imaging and histology, we demonstrate that Nfib conditional knockout mice have enlargement of the cerebral cortex but preservation of overall brain structure and interhemispheric connectivity. Based on our findings, we propose that haploinsufficiency of NFIB causes ID with macrocephaly.

Solute transport within grape berries inferred from the paramagnetic properties of manganese.

Tracer compounds used for studying solute transport should ideally have identical functions and transport properties to the molecules they are designed to mimic. Unfortunately, the xylem-mobile tracer compounds currently used to infer solute transport mechanisms in botanical specimens such as the fruit of the grapevine, Vitis vinifera L., are typically xenobiotic and have difficulty exiting the xylem during berry ripening. Here it is demonstrated that the transport of paramagnetic Mn ions can be indirectly observed within the grape berry, using relaxation magnetic resonance imaging (MRI). Mn ions from a 10mM Mn chloride solution were taken up into the grape berry via the pedicel and moved through the peripheral vasculature before exiting into surrounding pericarp tissue. Mn did not exit evenly across the berry, implying that the berry xylem influences which sites Mn exits the vasculature 'downstream' of the berry pedicel. It was also found that when the cellular membranes of pericarp tissues were disrupted, the distribution of Mn through the pericarp tissue became noticeably more homogenous. This indicates that the cellular membranes of extra-vascular cells affect the spatial distribution of Mn across the berry extra-vascular pericarp tissue upon exiting the grape berry vasculature.

Erratum to: Use of diffusion magnetic resonance imaging to correlate the developmental changes in grape berry tissue structure with water diffusion patterns.

[This corrects the article DOI: 10.1186/1746-4811-10-35.].

Use of diffusion magnetic resonance imaging to correlate the developmental changes in grape berry tissue structure with water diffusion patterns.

BACKGROUND: Over the course of grape berry development, the tissues of the berry undergo numerous morphological transformations in response to processes such as water and solute accumulation and cell division, growth and senescence. These transformations are expected to produce changes to the diffusion of water through these tissues detectable using diffusion magnetic resonance imaging (MRI). To assess this non-invasive technique diffusion was examined over the course of grape berry development, and in plant tissues with contrasting oil content. RESULTS: In this study, the fruit of Vitis vinfera L. cv. Semillon at seven different stages of berry development, from four weeks post-anthesis to over-ripe, were imaged using diffusion tensor and transverse relaxation MRI acquisition protocols. Variations in diffusive motion between these stages of development were then linked to known events in the morphological development of the grape berry. Within the inner mesocarp of the berry, preferential directions of diffusion became increasingly apparent as immature berries increased in size and then declined as berries progressed through the ripening and senescence phases. Transverse relaxation images showed radial striation patterns throughout the sub-tissue, initiating at the septum and vascular systems located at the centre of the berry, and terminating at the boundary between the inner and outer mesocarp. This study confirms that these radial patterns are due to bands of cells of alternating width that extend across the inner mesocarp. Preferential directions of diffusion were also noted in young grape seed nucelli prior to their dehydration. These observations point towards a strong association between patterns of diffusion within grape berries and the underlying tissue structures across berry development. A diffusion tensor image of a post-harvest olive demonstrated that the technique is applicable to tissues with high oil content. CONCLUSION: This study demonstrates that diffusion MRI is a powerful and information rich technique for probing the internal microstructure of plant tissues. It was shown that macroscopic diffusion anisotropy patterns correlate with the microstructure of the major pericarp tissues of cv. Semillon grape berries, and that changes in grape berry tissue structure during berry development can be observed.