The corpus callosum per se is the largest bundle of commissural fibers in the human brain. It consists of at least 200–300 million fibers connecting the right and left cerebral hemispheres together (Huang et al., 2005; Sakai et al., 2017). It plays important roles in transferring sensory, motor, and cognitive information between the right and left cerebral hemispheres (LaMantia and Rakic, 1990-9). Most of these fibers provide homotopic connections between all the mirror-imaged areas in the cerebral hemispheres (Huang et al., 2005).
Notwithstanding, heterotopic fibers that connect anatomically and functionally different regions of the cerebral cortex in an asymmetric manner are also present (Mooshagian, 2008).
Anatomically, the CC is divided into four distinct regions, consisting of the rostrum, genu, body, and splenium (Sakai et al., 2017). The genu is the most anterior region, near the frontal lobe, while the splenium is the most posterior area, near the occipital lobe. The rostrum is the inferior backward extension from the genu, and the body is the largest area of the CC, located between the genu and splenium (Jones, 1985).
An early review on studies of the corpus callosum found that a thicker corpus callosum in schizophrenia patients was associated with both more negative symptoms and earlier age of onset. As both of these are more common in males, it may be that corpus callosum abnormalities in schizophrenia are sex-dependent. Indeed, an exploratory meta-regression in a study showed that sex may explain differences in diffusion properties of the corpus callosum in schizophrenia.
These results provide compelling evidence for the hypothesis that the corpus callosum plays a key role in the specialization of language to the left hemisphere. In AgCC, cortical processing for language becomes distributed across the two hemispheres and becomes right hemisphere dominant in cAgCC, a functional change that is independent of handedness. The timing and magnitude of activity in the left hemisphere for the main components of the frontotemporal language network was comparable between the groups, with greater activity in the right hemisphere over the same time windows in AgCC for both auditory and visual stimuli. Interestingly, the time windows that manifest left hemispheric lateralization in neurotypical cohorts (Findlay et al., 2012) overlapped time windows that manifest right hemisphere activation in AgCC. This shift away from left hemisphere dominance in AgCC was unrelated to additional clinical diagnoses.
It is possible that there is a nonlinear relationship between callosal volume and language laterality exists in which, in extreme cases (such as abnormally large callosa or AgCC), the likelihood of functional asymmetry decreases. Given that the tasks being conducted here are designed to drive the general processes of language input and speech output, it is not clear which patterns of activity correspond to different linguistic processes (e.g., syntactic vs lexical processing) across the two tasks. Nonetheless, we demonstrate here the novel finding that the establishment of left hemisphere language lateralization is associated with normal callosal development. We further provide evidence that linguistic impairments in those born without this structure are associated with profound increases in activity in the right hemisphere. Because language is not the only lateralized process in the human brain, future studies are needed to address how other cognitive functions (such as spatial ability) are dependent on healthy callosal development.
It is known that response synchronization between neurons of homotopic areas from both cortical hemispheres disappear after callosotomy (Engel et al. 1991), indicating that interhemispheric communication has an integrative function coordinating distal equivalent circuits in a single computational unit (Schmidt et al. 2010). Nonetheless, evidence for a net inhibitory role of the corpus callosum also exists (Hlushchuk and Hari 2006; Reis et al. 2008; Beaulé et al. 2012; Palmer et al. 2012). Accordingly, it has been proposed that callosal axons sustain competition between contralateral ensembles, leading to lateral dominance (for a review on these two opposed hypothesis see Bloom and Hynd 2005; van der Knaap and van der Ham 2011).
The lack of a detailed description of the connectivity between callosal projecting neurons (CPNs) and their contralateral targets remains as a major limitation in our understanding of the functional role of the callosal transfer. Our aim was to fill this gap by studying the influence of the CPNs on contralateral cortical microcircuits. Despite several attempts have been done to characterize the impact of CPNs on contralateral circuits (Karayannis et al. 2007; Palmer et al. 2012; Lee et al. 2014; Rock and Apicella 2015), so far, this is the first study considering the contribution of this pathway within the entire columnar extension of the contralateral cortex. For this, we have performed a detailed electrophysiological screening across different categories of pyramidal and gabaergic neurons in the retrosplenial cortex, a high-order association area involved in spatial cognition and context recognition (Wolbers and Büchel 2005; Smith et al. 2012; Czajkowski et al. 2014; reviewed in Vann et al. 2009).
Our results suggest that the origin of the corpus callosum in early eutherian ancestors likely included the conservation of preexisting features of intra- and interhemispheric connectivity. Notably, humans with congenital absence of the corpus callosum, but with preserved interhemispheric integrative functions, often show compensatory wiring through the anterior commissure that resembles the noneutherian connectome (51). This suggests that, under certain unknown conditions, neocortical commissural neurons may exploit developmental plasticity of ancient mechanisms of axon guidance, resulting in functional interhemispheric circuits. Our findings provide a comparative framework to further elucidate the molecular underpinnings of interhemispheric wiring in individuals with and without a corpus callosum, as well as to investigate developmental hypotheses concerning the evolution of homologous circuits in the vertebrate brain.


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