Improving clinical interpretability of linear neuroimaging models through feature whitening

Linear models are widely used in computational neuroimaging to identify biomarkers associated with brain pathologies. However, interpreting the learned weights remains challenging, as they do not always yield clinically meaningful insights. This difficulty arises in part from the inherent correlation between brain regions, which causes linear weights to reflect shared rather than region-specific contributions. In particular, some groups of regions, including homologous structures in the left and right hemispheres, are known to exhibit strong anatomical correlations. In this work, we leverage this prior neuroanatomical knowledge to introduce a whitening approach applied to groups of regions with known shared variance, designed to disentangle overlapping information across correlated brain measures. We additionally propose a regularized variant that allows controlled tuning of the degree of decorrelation. We evaluate this method using region-of-interest features in two psychiatric classification tasks, distinguishing individuals with bipolar disorder or schizophrenia from healthy controls. Importantly, unlike PCA or ICA which use whitening as a dimensionality reduction step, our approach decorrelates anatomically informed pairs of neuroanatomical regions while retaining the full input signal, making it specifically suited for feature interpretation rather than feature selection. Our findings demonstrate that whitening improves the interpretability of model weights while preserving predictive performance, providing a robust framework for linking linear model outputs to neurobiological mechanisms.

How and why does deep ensemble coupled with transfer learning increase performance in bipolar disorder and schizophrenia classification?

Transfer learning (TL) and deep ensemble learning (DE) have recently been shown to outperform simple machine learning in classifying psychiatric disorders. However, there is still a lack of understanding as to why that is. This paper aims to understand how and why DE and TL reduce the variability of single-subject classification models in bipolar disorder (BD) and schizophrenia (SCZ). To this end, we investigated the training stability of TL and DE models. For the two classification tasks under consideration, we compared the results of multiple trainings with the same backbone but with different initializations. In this way, we take into account the epistemic uncertainty associated with the uncertainty in the estimation of the model parameters. It has been shown that the performance of classifiers can be significantly improved by using TL with DE. Based on these results, we investigate i) how many models are needed to benefit from the performance improvement of DE when classifying BD and SCZ from healthy controls, and ii) how TL induces better generalization, with and without DE. In the first case, we show that DE reaches a plateau when 10 models are included in the ensemble. In the second case, we find that using a pre-trained model constrains TL models with the same pre-training to stay in the same basin of the loss function. This is not the case for DL models with randomly initialized weights.