Abstract
Humans exhibit laterality preferences, with handedness being the most extensively studied. Accordingly, brain-handedness associations are well documented. However, laterality preferences extend beyond handedness to include other limbs and organs, such as footedness and eyedness. Despite these distinctions, brain-footedness and brain-eyedness associations using resting-state functional connectomes remain largely unexplored. We utilize two large datasets, the Human Connectome Project-Development (HCP-D) and Human Connectome Project-Aging (HCP-A), to study the associations between sidedness (i.e., handedness, footedness, and eyedness) and whole-brain functional connectomes. While hand and foot preferences were correlated significantly, they explained less than 40% of the variance, suggesting some distinctions between the measures. For both cohorts, significant associations between handedness and connectivity were observed (p<0.05, NBS corrected). Notable patterns include increased connectivity for left-handedness in the posterior temporal areas and right-handedness in cerebellar regions. In contrast, significant associations between footedness and connectivity were observed only in the HCP-A (p<0.05, NBS corrected) and not the HCP-D. These connectivity patterns were similar to the handedness results. No significant associations between eyedness and connectivity were observed for either group. Finally, we compared the effect size between brain-handedness and brain-footedness associations. A greater difference was found in the HCP-D. The two cohorts primarily differed in edge distribution in the prefrontal lobe, temporal lobe, and cerebellum. Overall, in adults, brain-handedness and brain-footedness associations were similar. However, in children to adolescents, brain-handedness and brain-footedness associations diverge, suggesting a developmental shift. Characterizing sidedness associations with whole-brain connectomes may provide important insights into understanding the motor and visual systems, rehabilitation and occupational therapy, and benchmarking normative variations in the connectome.
Significance Statement Lateral preferences stem from functional biases in brain hemispheres. However, studies associating brain connectivity to these predominant preferences have often been oversimplified to handedness. Although approximately 90% of the population is right-handed, other lateral preferences—like footedness and eyedness—show much lower and more varied distributions. This study aims to provide a foundational understanding of how broader lateral preferences might offer a more nuanced view of the brain's functional connectivity.
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