| Abstract: | The functional interaction between the brain’s two hemispheres includes a unique set of connections between corresponding regions in opposite hemispheres (i.e., homotopic regions) that are consistently reported to be exceptionally strong compared with other interhemispheric (i.e., heterotopic) connections. The strength of homotopic functional connectivity (FC) is thought to be mediated by the regions’ shared functional roles and their structural connectivity. Recently, homotopic FC was reported to be stable over time despite the presence of dynamic FC across both intrahemispheric and heterotopic connections. Here we build on this work by considering whether homotopic FC is also stable across conditions. We additionally test the hypothesis that strong and stable homotopic FC is supported by the underlying structural connectivity. Consistent with previous findings, interhemispheric FC between homotopic regions were significantly stronger in both humans and macaques. Across conditions, homotopic FC was most resistant to change and therefore was more stable than heterotopic or intrahemispheric connections. Across time, homotopic FC had significantly greater temporal stability than other types of connections. Temporal stability of homotopic FC was facilitated by direct anatomical projections. Importantly, temporal stability varied with the change in conductive properties of callosal axons along the anterior–posterior axis. Taken together, these findings suggest a notable role for the corpus callosum in maintaining stable functional communication between hemispheres.The brain’s capacity for processing information relies on a modular and hierarchical functional architecture that allows both functional segregation and integration (1, 2). Distributed processing occurs within segregated communities responsible for highly specialized functions, whereas more comprehensive functions require long-range integration across communities. This long-range integration is especially important for coordinating functions between the two hemispheres. Functional connectivity (FC), computed as the temporal correlation or covariance between regionwise signals, varies across different interhemispheric regions. FC is significantly stronger between homotopic regions than between heterotopic regions (3) and is greater than would be expected from the anatomical distance between the homotopic regions (4). This strong homotopic FC is thought to be mediated by the strong underlying structural connectivity of the corpus callosum (CC). Indeed, the majority of callosal fibers are between homotopic brain regions (5–7), and the loss of callosal integrity leads to a loss in homotopic FC (8, 9).Recently, a growing number of resting-state functional MRI (fMRI) studies have reported how FC varies over time (10). Flexibility in cognitive processing is thought to arise from the ability of certain regions to participate dynamically in different network configurations (11). For instance, interhemispheric functional interactions between different communities are highly variable over the course of a resting-state scan. Meanwhile, interhemispheric connections within the same community, especially homotopic connections, are temporally stable (12–14). Together, these findings suggest that interhemispheric coordination may occur predominantly via homotopic functional connections.FC also is known to vary between task and resting-state conditions (15). The extent to which interhemispheric coordination relies on homotopic functional connections across conditions remains to be determined. Moreover, whether interhemispheric coordination is mediated by the underlying structural connectivity has yet to be demonstrated empirically. In this study, we tested the hypothesis that FC between homotopic regions is stable across both time and conditions using blood oxygen level-dependent (BOLD) fMRI data collected from humans and macaques. We additionally used two approaches to examine the extent to which the stability of homotopic functional connections is mediated by the underlying anatomical projections. First, we directly compared macaque BOLD-fMRI data with structural connectivity data derived from axonal tract-tracing studies in macaque monkeys. Second, we compared the patterns of observed functional stability with known patterns of callosal fiber conductive properties in both humans and macaques. |
