Marc-André Schulz

Fabian Eitel, Marc-André Schulz, Moritz Seiler et al.

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.

Roshan Prakash Rane, JiHoon Kim, Arjun Umesha et al.

Deep Learning (DL) models have gained popularity in neuroimaging studies for predicting psychological behaviors, cognitive traits, and brain pathologies. However, these models can be biased by confounders such as age, sex, or imaging artifacts from the acquisition process. To address this, we introduce 'DeepRepViz', a two-part framework designed to identify confounders in DL model predictions. The first component is a visualization tool that can be used to qualitatively examine the final latent representation of the DL model. The second component is a metric called 'Con-score' that quantifies the confounder risk associated with a variable, using the final latent representation of the DL model. We demonstrate the effectiveness of the Con-score using a simple simulated setup by iteratively altering the strength of a simulated confounder and observing the corresponding change in the Con-score. Next, we validate the DeepRepViz framework on a large-scale neuroimaging dataset (n=12000) by performing three MRI-phenotype prediction tasks that include (a) predicting chronic alcohol users, (b) classifying participant sex, and (c) predicting performance speed on a cognitive task called 'trail making'. DeepRepViz identifies sex as a significant confounder in the DL model predicting chronic alcohol users (Con-score=0.35) and age as a confounder in the model predicting cognitive task performance (Con-score=0.3). In conclusion, the DeepRepViz framework provides a systematic approach to test for potential confounders such as age, sex, and imaging artifacts and improves the transparency of DL models for neuroimaging studies.

Nys Tjade Siegel, James H. Cole, Mohamad Habes et al.

Trustworthy interpretation of deep learning models is critical for neuroimaging applications, yet commonly used Explainable AI (XAI) methods lack rigorous validation, risking misinterpretation. We performed the first large-scale, systematic comparison of XAI methods on ~45,000 structural brain MRIs using a novel XAI validation framework. This framework establishes verifiable ground truth by constructing prediction tasks with known signal sources - from localized anatomical features to subject-specific clinical lesions - without artificially altering input images. Our analysis reveals systematic failures in two of the most widely used methods: GradCAM consistently failed to localize predictive features, while Layer-wise Relevance Propagation generated extensive, artifactual explanations that suggest incompatibility with neuroimaging data characteristics. Our results indicate that these failures stem from a domain mismatch, where methods with design principles tailored to natural images require substantial adaptation for neuroimaging data. In contrast, the simpler, gradient-based method SmoothGrad, which makes fewer assumptions about data structure, proved consistently accurate, suggesting its conceptual simplicity makes it more robust to this domain shift. These findings highlight the need for domain-specific adaptation and validation of XAI methods, suggest that interpretations from prior neuroimaging studies using standard XAI methodology warrant re-evaluation, and provide urgent guidance for practical application of XAI in neuroimaging.