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The Extended Frontal Aslant Tract (exFAT) is a recently described tractography-based extension of the Frontal Aslant Tract connecting Broca’s territory to both supplementary and pre-supplementary motor areas, and more anterior prefrontal regions. In this study, we aim to characterize the microstructural properties of the exFAT trajectories as a means to perform a laterality analysis to detect interhemispheric structural differences along the tracts using the Human Connectome Project (HCP) dataset. To that end, the bilateral exFAT was reconstructed for 3T and 7T HCP acquisitions in 120 randomly selected subjects. As a complementary exploration of the exFAT anatomy, we performed a white matter dissection of the exFAT trajectory of two ex-vivo left hemispheres that provide a qualitative assessment of the tract profiles. We assessed the lateralization structural differences in the exFAT by performing: (i) a laterality comparison between the mean microstructural diffusion-derived parameters for the exFAT trajectories, (ii) a laterality comparison between the tract profiles obtained by applying the Automated Fiber Quantification (AFQ) algorithm, and (iii) a cross-validated Machine Learning (ML) classifier analysis using single and combined tract profiles parameters for single-subject classification. The mean microstructural diffusion-derived parameter comparison showed statistically significant differences in mean FA values between left and right exFATs in the 3T sample. The diffusion parameters studied with the AFQ technique suggest that the inferiormost half of the exFAT trajectory has a hemispheric-dependent fingerprint of microstructural properties, with an increased measure of tissue hindrance in the orthogonal plane and a decreased measure of orientational dispersion along the main tract direction in the left exFAT compared to the right exFAT. The classification accuracy of the ML models showed a high agreement with the magnitude of those differences.

The extended frontal aslant tract (exFAT) is a tractography-based extension of the frontal aslant tract (FAT) which has been shown to be related with language and working memory performance in healthy human adults, but whether those functional implications map to structurally separate regions along its trajectory is still an open question. We present a tractography-informed Voxel-Based Morphometry procedure capable of detecting local tract-specific structural differences in white matter regions and apply it in two maximum variation sampling studies by comparing local differences in diffusion-derived microstructural parameters and fiber density along the exFAT territory between top performers and bottom performers in language and working memory tasks. In the right hemisphere we were able to detect, without prior constraints, a vertical frontal aslant component approximating the original FAT trajectory whose fiber density was significantly correlated with language (but not working memory) performance and an anterior cluster component corresponding to a distinct anterior frontal aslant component whose fiber density was significantly correlated with working memory (but not language) performance. The reported sub-division of the exFAT territory describes a set of frontal connections that are compatible with previously reported results on the Broca’s territory and frontal cortex hierarchical organization along an anterior-posterior gradient, suggesting that the exFAT could be part of a common neuroanatomical scaffold where language and working memory functions are integrated in the healthy human brain.

The extended frontal aslant tract (exFAT) is a tractography-based extension of the frontal aslant tract (FAT) which has been shown to be related with language and working memory performance in healthy human adults, but whether those functional implications map to structurally separate regions along its trajectory is still an open question. We present a tractography-informed Voxel-Based Morphometry procedure capable of detecting local tract-specific structural differences in white matter regions and apply it in two maximum variation sampling studies by comparing local differences in diffusion-derived microstructural parameters and fiber density along the exFAT territory between top performers and bottom performers in language and working memory tasks. In the right hemisphere we were able to detect, without prior constraints, a vertical frontal aslant component approximating the original FAT trajectory whose fiber density was significantly correlated with language (but not working memory) performance and an anterior cluster component corresponding to a distinct anterior frontal aslant component whose fiber density was significantly correlated with working memory (but not language) performance. The reported sub-division of the exFAT territory describes a set of frontal connections that are compatible with previously reported results on the Broca's territory and frontal cortex hierarchical organization along an anterior-posterior gradient, suggesting that the exFAT could be part of a common neuroanatomical scaffold where language and working memory functions are integrated in the healthy human brain. [ABSTRACT FROM AUTHOR]