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The architecture of functional lateralisation and its relationship to callosal connectivity in the human brain.

ABSTRACT: Functional lateralisation is a fundamental principle of the human brain. However, a comprehensive taxonomy of functional lateralisation and its organisation in the brain is missing. Here, we report the first complete map of functional hemispheric asymmetries in the human brain, reveal its low dimensional structure, and its relationship with structural inter-hemispheric connectivity. Our results suggest that the lateralisation of brain functions is distributed along four functional axes: symbolic communication, perception/action, emotion, and decision-making. The similarity between this finding and recent work on neurological symptoms give rise to new hypotheses on the mechanisms that support brain recovery after a brain lesion. We also report that cortical regions showing asymmetries in task-evoked activity have reduced connections with the opposite hemisphere. This latter result suggests that during evolution, brain size expansion led to functional lateralisation to avoid excessive conduction delays between the hemispheres.

SUBMITTER: Karolis VR

PROVIDER: S-EPMC6441088 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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The architecture of functional lateralisation and its relationship to callosal connectivity in the human brain.

Karolis Vyacheslav R VR Corbetta Maurizio M Thiebaut de Schotten Michel M

Nature communications 20190329 1

Functional lateralisation is a fundamental principle of the human brain. However, a comprehensive taxonomy of functional lateralisation and its organisation in the brain is missing. Here, we report the first complete map of functional hemispheric asymmetries in the human brain, reveal its low dimensional structure, and its relationship with structural inter-hemispheric connectivity. Our results suggest that the lateralisation of brain functions is distributed along four functional axes: symbolic ...[more]

PMID: 30926845

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Project description:Functional and structural connectivity alterations in short- and long-range projections have been reported across neurodevelopmental disorders (NDD). Interhemispheric callosal projection neurons (CPN) represent one of the major long-range projections in the brain, which are particularly important for higher-order cognitive function and flexibility. However, whether a causal relationship exists between interhemispheric connectivity alterations and cognitive deficits in NDD remains elusive. Here, we focused on CDKL5 Deficiency Disorder (CDD), a severe neurodevelopmental disorder caused by mutations in the X-linked Cyclin-dependent kinase-like 5 (CDKL5) gene. We found an increase in homotopic interhemispheric connectivity and functional hyperconnectivity across higher cognitive areas in adult male and female CDKL5-deficient mice by resting-state functional MRI (rs-fMRI) analysis. This was accompanied by an increase in the number of callosal synaptic inputs but decrease in local synaptic connectivity in the cingulate cortex of juvenile CDKL5-deficient mice, suggesting an impairment in excitatory synapse development and a differential role of CDKL5 across excitatory neuron subtypes. These deficits were associated with significant cognitive impairments in CDKL5 KO mice. Selective deletion of CDKL5 in the largest subtype of CPN likewise resulted in an increase of functional callosal inputs, without however significantly altering intracortical cingulate networks. Notably, such callosal-specific changes were sufficient to cause cognitive deficits. Finally, when CDKL5 was selectively re-expressed only in this CPN subtype, in otherwise CDKL5-deficient mice, it was sufficient to prevent the cognitive impairments of CDKL5 mutants. Together, these results reveal a novel role of CDKL5 by demonstrating that it is both necessary and sufficient for proper CPN connectivity and cognitive function and flexibility, and further validates a causal relationship between CPN dysfunction and cognitive impairment in a model of NDD.

Dataset Information

The architecture of functional lateralisation and its relationship to callosal connectivity in the human brain.

Publications

The architecture of functional lateralisation and its relationship to callosal connectivity in the human brain.

Similar Datasets

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