Defining reference models for population variation, and the ability to study individual deviations is essential for understanding inter-individual variability and its relation to the onset and progression of medical conditions. In this work, we assembled a reference cohort of neuroimaging data from 82 sites (N=58,836; ages 2-100) and use normative modeling to characterize lifespan trajectories of cortical thickness and subcortical volume. Models are validated against a manually quality checked subset (N=24,354) and we provide an interface for transferring to new data sources. We showcase the clinical value by applying the models to a transdiagnostic psychiatric sample (N=1,985), showing they can be used to quantify variability underlying multiple disorders whilst also refining case-control inferences. These models will be augmented with additional samples and imaging modalities as they become available. This provides a common reference platform to bind results from different studies and ultimately paves the way for personalized clinical decision making.

General cognitive ability (GCA) refers to a trait‐like ability that contributes to performance across diverse cognitive tasks. Identifying brain‐based markers of GCA has been a longstanding goal of cognitive and clinical neuroscience. Recently, predictive modeling methods have emerged that build whole‐brain, distributed neural signatures for phenotypes of interest. In this study, we employ a predictive modeling approach to predict GCA based on fMRI task activation patterns during the N ‐back working memory task as well as six other tasks in the Human Connectome Project dataset ( n = 967), encompassing 15 task contrasts in total. We found tasks are a highly effective basis for prediction of GCA: The 2 ‐ back versus 0 ‐ back contrast achieved a 0.50 correlation with GCA scores in 10‐fold cross‐validation, and 13 out of 15 task contrasts afforded statistically significant prediction of GCA. Additionally, we found that task contrasts that produce greater frontoparietal activation and default mode network deactivation—a brain activation pattern associated with executive processing and higher cognitive demand—are more effective in the prediction of GCA. These results suggest a picture analogous to treadmill testing for cardiac function: Placing the brain in a more cognitively demanding task state significantly improves brain‐based prediction of GCA.

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Resting state functional connectomes are massive and complex. It is an open question, however, whether connectomes differ across individuals in a correspondingly massive number of ways, or whether most differences take a small number of characteristic forms. We systematically investigated this question and found clear evidence of low-rank structure in which a modest number of connectomic components, around 50–150, account for a sizable portion of inter-individual connectomic variation. This number was convergently arrived at with multiple methods including estimation of intrinsic dimensionality and assessment of reconstruction of out-of-sample data. In addition, we show that these connectomic components enable prediction of a broad array of neurocognitive and clinical symptom variables at levels comparable to a leading method that is trained on the whole connectome. Qualitative observation reveals that these connectomic components exhibit extensive community structure reflecting interrelationships between intrinsic connectivity networks. We provide quantitative validation of this observation using novel stochastic block model-based methods. We propose that these connectivity components form an effective basis set for quantifying and interpreting inter-individual connectomic differences, and for predicting behavioral/clinical phenotypes.