Structural Fingerprinting of the Frontal Aslant Tract: Predicting Cognitive Control Capacity and Obsessive-Compulsive...

White matter of the human brain is influenced by common genetic variations and shaped by neural activity-dependent experiences. Variations in microstructure of cerebral white matter across individuals and even across fiber tracts might underlie differences in cognitive capacity and vulnerabilities to mental disorders. The frontoparietal and cingulo-opercular networks of the brain constitute the central system supporting cognitive functions, and functional connectivity of these networks has been used to distinguish individuals known as "functional fingerprinting." The frontal aslant tract (FAT) that passes through the two networks has been implicated in executive functions. However, whether FAT can be used as a "structural fingerprint" to distinguish individuals and predict an individual's cognitive function and dysfunction is unknown. Here we investigated the fingerprinting property of FAT microstructural profiles using three independent diffusion MRI datasets with repeated scans on human participants including both females and males. We found that diffusion and geometric profiles of FAT can be used to distinguish individuals with a high accuracy. Next, we demonstrated that fractional anisotropy in different FAT segments predicted distinct cognitive functions, including working memory, inhibitory control, and relational reasoning. Finally, we assessed the contribution of altered FAT microstructural profiles to cognitive dysfunction in unmedicated patients with obsessive-compulsive disorders. We found that the altered microstructure in FAT was associated with the severity of obsessive-compulsive symptoms. Collectively, our findings suggest that the microstructural profiles of FAT can identify individuals with a high accuracy and may serve as an imaging marker for predicting an individual's cognitive capacity and disease severity.SIGNIFICANCE STATEMENT The frontoparietal network and cingulo-opercular network of the brain constitute a dual-network architecture for human cognitive functions, and functional connectivity of these two networks can be used as a "functional fingerprint" to distinguish individuals. However, the structural underpinnings of these networks subserving individual heterogeneities in their functional connectivity and cognitive ability remain unknown. We show here that the frontal aslant tract (FAT) that passes through the two networks distinguishes individuals with a high accuracy. Further, we demonstrate that the diffusion profiles of FAT predict distinct cognitive functions in healthy subjects and are associated with the clinical symptoms in patients with obsessive-compulsive disorders. Our findings suggest that the FAT may serve as a unique structural fingerprint underlying individual cognitive capability.