Brain circuit–gene expression relationships and neuroplasticity of multisensory cortices in blind children

Abstract

Sensory deprivation reorganizes neurocircuits in the human brain. The biological basis of such neuroplastic adaptations remains elusive. In this study, we applied two complementary graph theory-based functional connectivity analyses, one to evaluate whole-brain functional connectivity relationships and the second to specifically delineate distributed network connectivity profiles downstream of primary sensory cortices, to investigate neural reorganization in blind children compared with sighted controls. We also examined the relationship between connectivity changes and neuroplasticity-related gene expression profiles in the cerebral cortex. We observed that multisensory integration areas exhibited enhanced functional connectivity in blind children and that this reorganization was spatially associated with the transcription levels of specific members of the cAMP Response Element Binding protein gene family. Using systems-level analyses, this study advances our understanding of human neuroplasticity and its genetic underpinnings following sensory deprivation.blindness | children | neuroplasticity | functional connectivity | CREB family N europlasticity is an intrinsic ability of the brain to modify and rewire itself following experiences (1). The study of neuroplastic reorganization in blind individuals offers a model through which neuroadaptive processes can be identified. For instance, cross-modal neuroplasticity is a mechanism by which blind individuals recruit visual-related cortices to process sensory information from other perceptual modalities (2-5). In addition to occipital regions, parietal and frontal multimodal integration regions of blind adults are capable of functional connectivity reorganization (6). These brain areas are part of a multimodal integration network that acts as a bridge integrating multisensory functions across cortical regions (7). Our group has previously characterized the hierarchical structure and central position of the multimodal integration network in adult blind subjects (6). Although this finding advances our understanding of how information from primary unimodal cortices is adaptively integrated into higher-order associative areas, it remains unclear if neuroplastic changes within multimodal integration areas also occur in blind children. Furthermore, in addition to clarifying the sites of prominent neuroplastic changes, the biological mechanisms through which neuroplastic alterations occur have yet to be fully elucidated in blind individuals.Concurrent advances in cellular and molecular biology and neuroimaging provide a unique opportunity to explore the interlinked relationships between genes and neural circuits (8). A neuroimaging endophenotype is informative because it is more closely related to the genetic end product than clinical or behavioral phenotypes (9). Thus, examining properties of systemslevel brain organization and cortical gene expression has great potential to expand our understanding of neuroplastic mechanisms, particularly if specific gene expression patt...

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