Functional Connectome Correlates of Laterality Preferences: Insights into Hand, Foot, and Eye Dominance across the Lifespan.

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, 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 <40% of the variance, suggesting some distinctions between measures. For both cohorts, significant associations between handedness connectivity were observed [ < 0.05, network-based statistics (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 handedness connectivity were observed only in the HCP-A ( < 0.05, NBS corrected) and not the HCP-D. 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.