Stable long-range interhemispheric coordination is supported by direct anatomical projections

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.functional connectivity | structural connectivity | homotopy | dynamics T he 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, ...

Cross-hemispheric dopamine projections have functional significance

“…The parabrachial nucleus is one source of neurotensinergic projections to the VTA (48) and projects bilaterally to midbrain dopamine neurons (49). Regardless of the mechanism, the synchronicity in dopamine release between hemispheres uncovered here establishes that chemical signaling, like physiological activity (50), is tightly coupled across the brain. Given that amphetamine-induced dopamine transients remained in the unilaterally lesioned animals, it is apparent that interhemispherical connectivity contributes to psychostimulant-induced dopamine fluctuations.…”

Disruptions of network connectivity predict impairment in multiple behavioral domains after stroke

“…Homotopic FC is more stable across time and across conditions than other types of functional connections (54). It is possible that our FC-deficit models load most heavily on interhemispheric FC because this stability enables greater fidelity in measurement of disruption.…”

Linking Functional Connectivity and Structural Connectivity Quantitatively: A Comparison of Methods

“…Positive correlation has been found between functional connectivity and structural connectivity within local areas in somatosensory cortex (Wang et al, 2013). Other studies, investigating the whole brain connections including longdistance ROIs, found that brain regions with direct structural connections also exhibited stable functional connectivity (Shen et al, 2012(Shen et al, , 2015. A lesion study in monkeys further showed that interhemispheric functional connectivity was severely reduced with resection of interhemispheric fiber connections.…”

“…Similarities between macaque brain networks and human brain networks have been suggested (Margulies et al, 2009;Mars et al, 2011;Shen et al, 2015). In macaques, whereas functional connectivity, quantified by cross correlation, was sometimes derived from fMRI data (Adachi et al, 2012;Deco et al, 2014;Margulies et al, 2009;Mars et al, 2011;Shen et al, 2012Shen et al, , 2015, structural connectivity was often based on tract tracing techniques, which are not possible in humans. The tracer molecules injected into the source brain region are absorbed and transported by axons to target brain regions, resulting in a tracer density map.…”

“…Those areas showing high tracer density are labeled as brain regions with strong structural connections to the source region, whereas areas showing zero or low tracer density are considered having none or weak structural connection to the source region. In the online macaque cortex anatomical connectivity database CoCoMac (CoCoMac.g-node.org), structural connections are classified according to four categories: no connection, light connection, moderate connection, and strong connection (Adachi et al, 2012;Deco et al, 2014;Shen et al, 2012Shen et al, , 2015. Positive correlation has been found between functional connectivity and structural connectivity within local areas in somatosensory cortex (Wang et al, 2013).…”