Multi-site Harmonization of MRI Data Uncovers Machine-learning Discrimination Capability in Barely Separable Populations: An Example from the ABIDE Dataset

Machine Learning (ML) techniques have been widely used in Neuroimaging studies of Autism Spectrum Disorders (ASD) both to identify possible brain alterations related to this condition and to evaluate the predictive power of brain imaging modalities. The collection and public sharing of large imaging samples has favored an even greater diffusion of the use of ML-based analyses. However, multi-center data collections may suffer the batch effect, which, especially in case of Magnetic Resonance Imaging (MRI) studies, should be curated to avoid confounding effects for ML classifiers and masking biases. This is particularly important in the study of barely separable populations according to MRI data, such as subjects with ASD compared to controls with typical development (TD). Here, we show how the implementation of a harmo- nization protocol on brain structural features unlocks the case-control ML separation capability in the analysis of a multi-center MRI dataset. This effect is demonstrated on the ABIDE data collection, involving subjects encompassing a wide age range. After data harmonization, the overall ASD vs. TD discrimination capability by a Random Forest (RF) classifier improves from a very low performance (AUC = 0.58 ± 0.04) to a still low, but reasonably significant AUC = 0.67 ± 0.03. The performances of the RF classifier have been evaluated also in the age-specific subgroups of children, adolescents and adults, obtaining AUC = 0.62 ± 0.02, AUC = 0.65 ± 0.03 and AUC = 0.69 ± 0.06, respectively. Specific and consistent patterns of anatomical differences related to the ASD condition have been identified for the three different age subgroups.