Connectivity profile laterality in corticostriatal functional circuitry: a fingerprinting approach

ABSTRACT An abnormal magnitude of hemispheric difference (i.e. laterality) in corticostriatal circuits is a shared feature of numerous neurodevelopmental and psychiatric disorders. Detailed quantitation and regional localization of corticostriatal laterality in normative samples stands to further the understanding of hemispheric differences in healthy and disease states. Here, we used a fingerprinting approach to quantify “functional connectivity profile laterality” – the overall magnitude by which a voxel’s profile of connectivity with homotopic regions of the ipsilateral and contralateral cortex differs – in the striatum. Laterality magnitude heatmaps revealed “laterality hotspots” – constituting outliers in the voxel-wise distribution –in the right ventrolateral putamen and left central caudate. Findings were replicated in an independent sample, with significant (p<0.05) spatial overlap observed between the location of the laterality hotspots across samples, as measured via Dice coefficients. At both hotspots, a primary driver of overall laterality was the difference in striatal connectivity strength with the right and left pars opercularis of the inferior frontal gyrus. Right and left striatum laterality magnitude maps were found to significantly differ (p<0.05) at the hotspot locations. Moreover, using subjects’ left, but not right, striatum laterality magnitude maps, a support vector machine trained on a discovery sample (n=77) and tested on a replication sample (n=77) significantly predicted (r=0.25, p=0.028) subject performance on a language task, known for its lateralized nature. Laterality magnitude maps remained consistent across different cortical atlas parcellations and did not differ significantly between right-handed and left-handed individuals. In sum, meaningful variation in functional connectivity profile laterality – both spatially within the striatum and across subjects – is evident in corticostriatal circuits. Findings provide a basis to examine corticostriatal connectivity profile laterality in psychiatric illness.