Weak but influential: Nonlinear contributions of structural connectivity to human cognitive abilities and brain functions

Abstract: Diverse human cognitive abilities are rooted in brain structural connectivity which has weights spanning several orders of magnitude. However, due to false-positive challenges in tractography, weak connectivity has been often treated as noise and ignored - despite its prevalence across mammalian brains. Here we show that weak connectivity significantly predicts human cognitive abilities and supports brain functions through amplification of its small weight in a nonlinear manner. Using the Human Connectome Project dataset (n=999) and multiple tractography algorithms, we constructed the whole-brain structural connectivity with heterogeneous weights of streamline numbers. We found that weak connectivity involves high individual variability and significantly predicts general cognitive ability and memory in individuals, and it is also critical for whole-brain dynamic simulation and structure-function coupling. Importantly, fusing two post-tractography filtering methods of streamlines potentially results in more reliable connectivity that preserves weak links and outperforms conventional thresholding in predicting cognitive abilities and functional connectivity. At the network level, weak connectivity expands the operational capacity of brain networks to enhance both global integration and fine-grained segregation, thereby supporting a functional balance essential for cognitive abilities. Finally, we identified a specific type of weak connectivity mainly linking visual/motor to limbic areas with negative gene co-expression, which has a disproportionately large impact on cognitive predictions and network dynamics.