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• Individuals remain poorly predictable from population-level analyses of the brain. • The fidelity limits data scale, compute, and model flexibility impose are unknown. • We quantify these limits in multimodal, multitarget analyses across 23810 people. • We show a radical change in modelling regimes is needed for individual prediction. Our knowledge of the organisation of the human brain at the population-level is yet to translate into power to predict functional differences at the individual-level, limiting clinical applications and casting doubt on the generalisability of inferred mechanisms. It remains unknown whether the difficulty arises from the absence of individuating biological patterns within the brain, or from limited power to access them with the models and compute at our disposal. Here we comprehensively investigate the resolvability of such patterns with data and compute at unprecedented scale. Across 23 810 unique participants from UK Biobank, we systematically evaluate the predictability of 25 individual biological characteristics, from all available combinations of structural and functional neuroimaging data. Over 4526 GPU*hours of computation, we train, optimize, and evaluate out-of-sample 700 individual predictive models, including fully-connected feed-forward neural networks of demographic, psychological, serological, chronic disease, and functional connectivity characteristics, and both uni- and multi-modal 3D convolutional neural network models of macro- and micro-structural brain imaging. We find a marked discrepancy between the high predictability of sex (balanced accuracy 99.7%), age (mean absolute error 2.048 years, R2 0.859), and weight (mean absolute error 2.609Kg, R2 0.625), for which we set new state-of-the-art performance, and the surprisingly low predictability of other characteristics. Neither structural nor functional imaging predicted an individual's psychology better than the coincidence of common chronic disease (p < 0.05). Serology predicted chronic disease (p < 0.05) and was best predicted by it (p < 0.001), followed by structural neuroimaging (p < 0.05). Our findings suggest either more informative imaging or more powerful models will be needed to decipher individual level characteristics from the human brain. We make our models and code openly available. [ABSTRACT FROM AUTHOR]

Brain age, most commonly inferred from T1-weighted magnetic resonance images (T1w MRI), is a robust biomarker of brain health and related diseases. Superior accuracy in brain age prediction, often falling within a 2–3 year range, is achieved predominantly through deep neural networks. However, comparing study results is difficult due to differences in datasets, evaluation methodologies and metrics. Addressing this, we introduce Brain Age Standardized Evaluation (BASE), which includes (i) a standardized T1w MRI dataset including multi-site, new unseen site, test-retest and longitudinal data, and an associated (ii) evaluation protocol, including repeated model training and upon based comprehensive set of performance metrics measuring accuracy, robustness, reproducibility and consistency aspects of brain age predictions, and (iii) statistical evaluation framework based on linear mixed-effects models for rigorous performance assessment and cross-comparison. To showcase BASE, we comprehensively evaluate four deep learning based brain age models, appraising their performance in scenarios that utilize multi-site, test-retest, unseen site, and longitudinal T1w brain MRI datasets. Ensuring full reproducibility and application in future studies, we have made all associated data information and code publicly accessible at https://github.com/AralRalud/BASE.git. • Standardized public multi-site, unseen site, test-retest and longitudinal MR datasets. • Evaluation protocol including repeated training of the brain age prediction models. • Metrics for accuracy, robustness, reproducibility and consistency evaluation. • Statistical evaluation framework based on linear mixed-effects models. • Fully reproducible study with the dataset information and publicly available code. [ABSTRACT FROM AUTHOR]

• Applied deep learning to sex classification in UK BioBank fMRI connectomes. • Deep learning classifies sex better in resting-state than in task fMRI. • Algorithm to balance out multiple confounds from an fMRI dataset. • Adapted two deep learning visualization methods to fMRI connectome classification. • Analyzed role of three brain a priori networks in sex classification. Classification of whole-brain functional connectivity MRI data with convolutional neural networks (CNNs) has shown promise, but the complexity of these models impedes understanding of which aspects of brain activity contribute to classification. While visualization techniques have been developed to interpret CNNs, bias inherent in the method of encoding abstract input data, as well as the natural variance of deep learning models, detract from the accuracy of these techniques. We introduce a stochastic encoding method in an ensemble of CNNs to classify functional connectomes by sex. We applied our method to resting-state and task data from the UK BioBank, using two visualization techniques to measure the salience of three brain networks involved in task- and resting-states, and their interaction. To regress confounding factors such as head motion, age, and intracranial volume, we introduced a multivariate balancing algorithm to ensure equal distributions of such covariates between classes in our data. We achieved a final AUROC of 0.8459. We found that resting-state data classifies more accurately than task data, with the inner salience network playing the most important role of the three networks overall in classification of resting-state data and connections to the central executive network in task data. [ABSTRACT FROM AUTHOR]