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. 2025 Oct 28;122(43):e2520190122.
doi: 10.1073/pnas.2520190122. Epub 2025 Oct 21.

Full interhemispheric integration sustained by a fraction of posterior callosal fibers

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Free article

Full interhemispheric integration sustained by a fraction of posterior callosal fibers

Tyler Santander et al. Proc Natl Acad Sci U S A. .
Free article

Abstract

The dynamic integration of the lateralized and specialized capacities of the two cerebral hemispheres constitutes a hallmark feature of human brain function. This interhemispheric exchange of information critically depends upon the corpus callosum. Classical anatomical descriptions of callosal organization outline a topographic gradient from front to back, such that specific transcallosal fibers support distinct aspects of integrated brain function. Here, we present a challenge to this conventional model. Using neuroimaging data obtained from a new cohort of adult corpus callosotomy patients, we leverage modern network neuroscience techniques to show that full interhemispheric integration can be achieved via a small proportion of posterior callosal fibers. Partial callosotomy patients with spared callosal fibers retained widespread patterns of interhemispheric functional connectivity and showed no signs of behavioral disconnection, even with only 1 cm of the splenium intact. Conversely, only complete callosotomy patients demonstrated sweeping disruptions of interhemispheric network architectures, aligning with disconnection syndromes long-thought to reflect diminished information propagation and communication across the brain. These findings motivate an evolving mechanistic understanding of synchronized interhemispheric neural activity for large-scale human brain function and behavior.

Keywords: brain networks; corpus callosum; functional connectivity; resting-state; split-brain.

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Conflict of interest statement

Competing interests statement:The authors declare no competing interest.

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