Title: Reorganization of thalamocortical connections in congenitally blind humans Running title: Thalamic plasticity in congenital blindness

Evidence of cross-modal plasticity in blind individuals has been reported over the past decades showing that non-visual information is carried and processed by ‘visual’ brain structures. This feature of the blind brain makes it a pivotal model to explore the limits and mechanisms of brain plasticity. However, despite multiple efforts, the structural underpinnings of cross-modal plasticity in congenitally blind individuals remain unclear. Using advanced neuroimaging techniques, we mapped thalamocortical connectivity and assessed cortical thickness and integrity of white matter of ten congenitally blind individuals and ten sighted controls. We hypothesized an aberrant thalamocortical pattern of connectivity taking place in the absence of visual stimuli from birth as a potential mechanism of cross-modal plasticity. In addition to the increased cortical thickness of the primary visual cortex and reduced integrity of visual white matter bundles, we observed structural connectivity changes between the thalamus and both occipital and temporal cortices. Specifically, the thalamic territory dedicated to connections with the occipital cortex was found to be smaller and displayed weaker connectivity in congenitally blind individuals, whereas the one that connects with the temporal cortex showed greater volume and stronger connectivity when compared to sighted controls. The abnormal pattern of thalamocortical connectivity included the lateral and medial geniculate nuclei and the pulvinar nucleus. For the first time in humans, a remapping of structural thalamocortical connections involving both unimodal and multimodal thalamic nuclei has been demonstrated, shedding light on the possible mechanisms of cross-modal plasticity in humans. Future studies should employ neurophysiologic approaches to explore the functional relevance of present findings.