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Agenesis of the corpus callosum: genetic, developmental and functional aspects of connectivity. Nat Rev Neurosci 8:287-299

California Institute of Technology, MC 228-77 Pasadena, California 91125, USA.
Nature reviews Neuroscience (Impact Factor: 31.43). 05/2007; 8(4):287-99. DOI: 10.1038/nrn2107
Source: PubMed

ABSTRACT

Agenesis of the corpus callosum (AgCC), a failure to develop the large bundle of fibres that connect the cerebral hemispheres, occurs in 1:4000 individuals. Genetics, animal models and detailed structural neuroimaging are now providing insights into the developmental and molecular bases of AgCC. Studies using neuropsychological, electroencephalogram and functional MRI approaches are examining the resulting impairments in emotional and social functioning, and have begun to explore the functional neuroanatomy underlying impaired higher-order cognition. The study of AgCC could provide insight into the integrated cerebral functioning of healthy brains, and may offer a model for understanding certain psychiatric illnesses, such as schizophrenia and autism.

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Available from: Lynn K Paul
    • "Another morphological abnormality featured in Maoa KO mice concerns the reduced thickness of the rostral portion of the corpus callosum (Bortolato et al., 2013a). This aberrance, which further suggests connectivity alterations in the frontal pole of the cortex, may lead to impairments in the interhemispheric processing of emotional responses to conflict and social stimuli (Paul et al., 2007;Schutter and Harmon-Jones, 2013), thereby contributing to the maladaptive responses to neutral and threatening stimuli in these animals (Godar et al., 2011). In line with this idea, reductions in callosal thickness have been evidenced in psychopathic, antisocial subjects (Raine et al., 2003). "
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    ABSTRACT: Drawing upon the recent resurgence of biological criminology, several studies have highlighted a critical role for genetic factors in the ontogeny of antisocial and violent conduct. In particular, converging lines of evidence have documented that these maladaptive manifestations of aggression are influenced by monoamine oxidase A (MAOA), the enzyme that catalyzes the degradation of brain serotonin, norepinephrine and dopamine. The interest on the link between MAOA and aggression was originally sparked by Han Brunner's discovery of a syndrome characterized by marked antisocial behaviors in male carriers of a nonsense mutation of this gene. Subsequent studies showed that MAOA allelic variants associated with low enzyme activity moderate the impact of early-life maltreatment on aggression propensity. In spite of overwhelming evidence pointing to the relationship between MAOA and aggression, the neurobiological substrates of this link remain surprisingly elusive; very little is also known about the interventions that may reduce the severity of pathological aggression in genetically predisposed subjects. Animal models offer a unique experimental tool to investigate these issues; in particular, several lines of transgenic mice harboring total or partial loss-of-function Maoa mutations have been shown to recapitulate numerous psychological and neurofunctional endophenotypes observed in humans. This review summarizes the current knowledge on the link between MAOA and aggression; in particular, we will emphasize how an integrated translational strategy coordinating clinical and preclinical research may prove critical to elucidate important aspects of the pathophysiology of aggression, and identify potential targets for its diagnosis, prevention and treatment.
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    • "Among them, the Disrupted-in-Schizophrenia 1 (DISC1) gene, named because of its possible role in schizophrenia and related disorders (Millar et al., 2000), was found to be highly expressed in the developing CC of embryonic mice. Osbun and colleagues (2011) also identified a variant form of the DISC1 gene, possibly pathogenic, in 144 AgCC patients, further suggesting an important role of this gene in the development of the CC and in the etiology of AgCC (Osbun et al., 2011; Paul et al., 2007). Since AgCC is an heterogeneous condition, symptoms can vary greatly between affected individuals, ranging from relative absence to severe impairment requiring special education and assistance in every day living (Paul et al., 2004; Siffredi et al., 2013). "
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    ABSTRACT: Agenesis of the corpus callosum (AgCC) is a congenital malformation that can occur in isolation or in association with other neurological conditions. Although the behavioral manifestations associated with AgCC have been widely studied, the effects of complete absence of the corpus callosum (CC) on cerebral cortex anatomy are still not completely understood. In this study, cortical thickness in adults with complete AgCC was compared to a group of healthy controls. Results showed highly variable patterns of cortical thickness in AgCC individuals, with few areas showing significant and consistent alterations including primary visual cortex, primary somatosensory cortex and primary motor cortex. These results suggest relatively limited effects of AgCC on cortical morphology, which are mostly restricted to primary sensory and motor areas.
    Full-text · Article · Sep 2015 · Neuropsychologia
    • "In a critical experiment, we than tested in a second approach, whether this contralaterally induced iM1 suppression is absent in patients with AgCC. AgCC is a rare condition, in which callosal fibers are congenitally completely or partially absent, caused by different genetic or environmental factors during prenatal callosal development [15]. As a consequence AgCC patients usually show prolonged visual interhemispheric transfer times [16] [17] and deficiencies in different higher cognitive abilities, where interhemispheric integration is important [18] [19]. "
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    ABSTRACT: During unilateral hand movements the activity of the contralateral primary motor cortex (cM1) is increased while the activity of the ipsilateral M1 (iM1) is decreased. A potential explanation for this asymmetric activity pattern is transcallosal cM1-to-iM1 inhibitory control. To test this hypothesis, we examined interhemispheric motor inhibition in acallosal patients. We measured fMRI activity in iM1 and cM1 in acallosal patients during unilateral hand movements and compared their motor activity pattern to that of healthy controls. In controls, fMRI activation in cM1 was significantly higher than in iM1, reflecting a normal differential task-related M1 activity. Additional functional connectivity analysis revealed that iM1 activity was strongly suppressed by cM1. Furthermore, DTI analysis indicated that this contralaterally induced suppression was mediated by microstructural properties of specific callosal fibers interconnecting both M1s. In contrast, acallosal patients did not show a clear differential activity pattern between cM1 and iM1. The more symmetric pattern was due to an elevated task-related iM1 activity in acallosal patients, which was significantly higher than iM1 activity in a subgroup of gender and age-matched controls. Also, interhemispheric motor suppression was completely absent in acallosal patients. These findings suggest that absence of callosal connections reduces inhibitory interhemispheric motor interactions between left and right M1. This effect may reveal novel aspects of mechanisms in communication of two hemispheres and establishment of brain asymmetries in general. Copyright © 2015. Published by Elsevier B.V.
    No preview · Article · Jul 2015 · Behavioural brain research
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