Several recent studies have optimized deep neural networks to learn high-dimensional relationships linking structural and functional connectivity across the human connectome. However, the extent to which these models recapitulate individual-specific characteristics of resting-state functional brain networks remains unclear. A core concern relates to whether current individual predictions outperform simple benchmarks such as group averages and null conditions. Here, we consider two measures to statistically evaluate whether functional connectivity predictions capture individual effects. We revisit our previously published functional connectivity predictions for 1,000 healthy adults and provide multiple lines of evidence supporting that our predictions successfully capture subtle individual-specific variation in connectivity. While predicted individual effects are statistically significant and outperform several benchmarks, we find that effect sizes are small (i.e., 8%–11% improvement relative to group-average benchmarks). As such, initial expectations about individual prediction performance expressed by us and others may require moderation. We conclude that individual predictions can significantly outperform appropriate benchmark conditions and we provide several recommendations for future studies in this area. Future studies should statistically assess the individual prediction performance of their models using one of the measures and benchmarks provided here. Author Summary Functional and structural brain networks share considerable overlap in network architecture. However, it remains debated whether deep neural networks can be trained to predict an individual's functional brain network from their structural connectome. We demonstrate that individual variability in functional brain connectivity can be successfully predicted from an individual's connectome, although prediction performance is modest when benchmarked against appropriate null models. We provide recommendations for future studies aiming to evaluate such predictions, specifically considering the impact of Riemann geometry, adjustments for cross-validation induced dependence and standardization. Accurate prediction models will enable extrapolation of functional networks for individuals without empirically acquired functional MRI data or noisy data. They may also facilitate digital simulations of the potential functional consequences arising from pathological changes in the connectome.

The connectome provides the structural substrate facilitating communication between brain regions. We aimed to establish whether accounting for polysynaptic communication in structural connectomes would improve prediction of interindividual variation in behavior as well as increase structure-function coupling strength. Connectomes were mapped for 889 healthy adults participating in the Human Connectome Project. To account for polysynaptic signaling, connectomes were transformed into communication matrices for each of 15 different network communication models. Communication matrices were (a) used to perform predictions of five data-driven behavioral dimensions and (b) correlated to resting-state functional connectivity (FC). While FC was the most accurate predictor of behavior, communication models, in particular communicability and navigation, improved the performance of structural connectomes. Communication also strengthened structure-function coupling, with the navigation and shortest paths models leading to 35–65% increases in association strength with FC. We combined behavioral and functional results into a single ranking that provides insight into which communication models may more faithfully recapitulate underlying neural signaling patterns. Comparing results across multiple connectome mapping pipelines suggested that modeling polysynaptic communication is particularly beneficial in sparse high-resolution connectomes. We conclude that network communication models can augment the functional and behavioral predictive utility of the human structural connectome. Author Summary Brain network communication models aim to describe the patterns of large-scale neural signaling that facilitate functional interactions between brain regions. While information can be directly communicated between anatomically connected regions, signaling between disconnected areas must occur via a sequence of intermediate regions. We investigated a number of candidate models of connectome communication and found that they improved structure-function coupling and the extent to which structural connectomes can predict interindividual variation in behavior. Comparing the behavioral and functional predictive utility of different models provided initial insight into which conceptualizations of network communication may more faithfully recapitulate biological neural signaling. Our results suggest network communication models as a promising avenue to unite our understanding of brain structure, brain function, and human behavior.