Promises and pitfalls of deep neural networks in neuroimaging-based psychiatric research

By promising more accurate diagnostics and individual treatment recommendations, deep neural networks and in particular convolutional neural networks have advanced to a powerful tool in medical imaging. Here, we first give an introduction into methodological key concepts and resulting methodological promises including representation and transfer learning, as well as modelling domain-specific priors. After reviewing recent applications within neuroimaging-based psychiatric research, such as the diagnosis of psychiatric diseases, delineation of disease subtypes, normative modeling, and the development of neuroimaging biomarkers, we discuss current challenges. This includes for example the difficulty of training models on small, heterogeneous and biased data sets, the lack of validity of clinical labels, algorithmic bias, and the influence of confounding variables.

Classification of Major Depressive Disorder via Multi-Site Weighted LASSO Model

Large-scale collaborative analysis of brain imaging data, in psychiatry and neu-rology, offers a new source of statistical power to discover features that boost ac-curacy in disease classification, differential diagnosis, and outcome prediction. However, due to data privacy regulations or limited accessibility to large datasets across the world, it is challenging to efficiently integrate distributed information. Here we propose a novel classification framework through multi-site weighted LASSO: each site performs an iterative weighted LASSO for feature selection separately. Within each iteration, the classification result and the selected features are collected to update the weighting parameters for each feature. This new weight is used to guide the LASSO process at the next iteration. Only the fea-tures that help to improve the classification accuracy are preserved. In tests on da-ta from five sites (299 patients with major depressive disorder (MDD) and 258 normal controls), our method boosted classification accuracy for MDD by 4.9% on average. This result shows the potential of the proposed new strategy as an ef-fective and practical collaborative platform for machine learning on large scale distributed imaging and biobank data.

Nonlinear functional mapping of the human brain

The field of neuroimaging has truly become data rich, and novel analytical methods capable of gleaning meaningful information from large stores of imaging data are in high demand. Those methods that might also be applicable on the level of individual subjects, and thus potentially useful clinically, are of special interest. In the present study, we introduce just such a method, called nonlinear functional mapping (NFM), and demonstrate its application in the analysis of resting state fMRI from a 242-subject subset of the IMAGEN project, a European study of adolescents that includes longitudinal phenotypic, behavioral, genetic, and neuroimaging data. NFM employs a computational technique inspired by biological evolution to discover and mathematically characterize interactions among ROI (regions of interest), without making linear or univariate assumptions. We show that statistics of the resulting interaction relationships comport with recent independent work, constituting a preliminary cross-validation. Furthermore, nonlinear terms are ubiquitous in the models generated by NFM, suggesting that some of the interactions characterized here are not discoverable by standard linear methods of analysis. We discuss one such nonlinear interaction in the context of a direct comparison with a procedure involving pairwise correlation, designed to be an analogous linear version of functional mapping. We find another such interaction that suggests a novel distinction in brain function between drinking and non-drinking adolescents: a tighter coupling of ROI associated with emotion, reward, and interoceptive processes such as thirst, among drinkers. Finally, we outline many improvements and extensions of the methodology to reduce computational expense, complement other analytical tools like graph-theoretic analysis, and allow for voxel level NFM to eliminate the necessity of ROI selection.