This study shows that every individual has a unique pattern of functional connections between brain regions. This functional connectivity profile acts as a ‘fingerprint’ that can accurately identify the individual from a large group. Furthermore, an individual's connectivity profile can predict his or her level of fluid intelligence. Functional magnetic resonance imaging (fMRI) studies typically collapse data from many subjects, but brain functional organization varies between individuals. Here we establish that this individual variability is both robust and reliable, using data from the Human Connectome Project to demonstrate that functional connectivity profiles act as a 'fingerprint' that can accurately identify subjects from a large group. Identification was successful across scan sessions and even between task and rest conditions, indicating that an individual's connectivity profile is intrinsic, and can be used to distinguish that individual regardless of how the brain is engaged during imaging. Characteristic connectivity patterns were distributed throughout the brain, but the frontoparietal network emerged as most distinctive. Furthermore, we show that connectivity profiles predict levels of fluid intelligence: the same networks that were most discriminating of individuals were also most predictive of cognitive behavior. Results indicate the potential to draw inferences about single subjects on the basis of functional connectivity fMRI.

Although attentional abilities vary widely and have profound everyday effects, a standardized measure of these abilities is lacking. This study introduces a new fMRI measure based on patterns of whole-brain connectivity, which predicts adults' attention performance and children's ADHD symptoms from data acquired while individuals are resting in the scanner. Although attention plays a ubiquitous role in perception and cognition, researchers lack a simple way to measure a person's overall attentional abilities. Because behavioral measures are diverse and difficult to standardize, we pursued a neuromarker of an important aspect of attention, sustained attention, using functional magnetic resonance imaging. To this end, we identified functional brain networks whose strength during a sustained attention task predicted individual differences in performance. Models based on these networks generalized to previously unseen individuals, even predicting performance from resting-state connectivity alone. Furthermore, these same models predicted a clinical measure of attention—symptoms of attention deficit hyperactivity disorder—from resting-state connectivity in an independent sample of children and adolescents. These results demonstrate that whole-brain functional network strength provides a broadly applicable neuromarker of sustained attention.

Recent work has begun to relate individual differences in brain functional organization to human behaviors and cognition, but the best brain state to reveal such relationships remains an open question. In two large, independent data sets, we here show that cognitive tasks amplify trait-relevant individual differences in patterns of functional connectivity, such that predictive models built from task fMRI data outperform models built from resting-state fMRI data. Further, certain tasks consistently yield better predictions of fluid intelligence than others, and the task that generates the best-performing models varies by sex. By considering task-induced brain state and sex, the best-performing model explains over 20% of the variance in fluid intelligence scores, as compared to <6% of variance explained by rest-based models. This suggests that identifying and inducing the right brain state in a given group can better reveal brain-behavior relationships, motivating a paradigm shift from rest- to task-based functional connectivity analyses.

Best practices are currently being developed for the acquisition and processing of resting-state magnetic resonance imaging data used to estimate brain functional organization—or “functional connectivity.” Standards have been proposed based on test–retest reliability, but open questions remain. These include how amount of data per subject influences whole-brain reliability, the influence of increasing runs versus sessions, the spatial distribution of reliability, the reliability of multivariate methods, and, crucially, how reliability maps onto prediction of behavior. We collected a dataset of 12 extensively sampled individuals (144 min data each across 2 identically configured scanners) to assess test–retest reliability of whole-brain connectivity within the generalizability theory framework. We used Human Connectome Project data to replicate these analyses and relate reliability to behavioral prediction. Overall, the historical 5-min scan produced poor reliability averaged across connections. Increasing the number of sessions was more beneficial than increasing runs. Reliability was lowest for subcortical connections and highest for within-network cortical connections. Multivariate reliability was greater than univariate. Finally, reliability could not be used to improve prediction; these findings are among the first to underscore this distinction for functional connectivity. A comprehensive understanding of test–retest reliability, including its limitations, supports the development of best practices in the field.

Establishing brain-behavior associations that map brain organization to phenotypic measures and generalize to novel individuals remains a challenge in neuroimaging. Predictive modeling approaches that define and validate models with independent datasets offer a solution to this problem. While these methods can detect novel and generalizable brain-behavior associations, they can be daunting, which has limited their use by the wider connectivity community. Here, we offer practical advice and examples based on functional magnetic resonance imaging (fMRI) functional connectivity data for implementing these approaches. We hope these ten rules will increase the use of predictive models with neuroimaging data.