Effective connectivity between the cerebellum and fronto-temporal regions correctly classify major depressive...

Major Depressive Disorder (MDD) diagnosis mainly relies on subjective self-reporting and clinical assessments. Resting-state functional magnetic resonance imaging (rs-fMRI) and its analysis of Effective Connectivity (EC) offer a quantitative approach to understand the directional interactions between brain regions, presenting a potential objective method for MDD classification.

Granger causality analysis was used to extract EC features from a large, multi-site rs-fMRI dataset of MDD patients. The ComBat algorithm was applied to adjust for site differences, while multivariate linear regression was employed to control for age and sex differences. Discriminative EC features for MDD were identified using two-sample t-tests and model-based feature selection, with the LightGBM algorithm being used for classification. The performance and generalizability of the model was evaluated using nested five-fold cross-validation and tested for generalizability on an independent dataset.

Ninety-seven EC features belonging to the cerebellum and front-temporal regions were identified as highly discriminative for MDD. The classification model using these features achieved an accuracy of 94.35 %, with a sensitivity of 93.52 % and specificity of 95.25 % in cross-validation. Generalization of the model to an independent dataset resulted in an accuracy of 94.74 %, sensitivity of 90.59 %, and specificity of 96.75 %.

The study demonstrates that EC features from rs-fMRI can effectively discriminate MDD from healthy controls, suggesting that EC analysis could be a valuable tool in assisting the clinical diagnosis of MDD. This method shows promise in enhancing the objectivity of MDD diagnosis through the use of neuroimaging biomarkers.