Quadrato Motor Training in Parkinson’s Disease: Resting-State fMRI Changes and Exploratory Whole-Brain Radiomics

Parkinson’s disease (PD) may benefit from non-pharmacological motor–cognitive rehabilitation, but sensitive neuroimaging markers of training-related brain changes remain limited. This study investigated whether 4 weeks of daily Quadrato Motor Training (QMT) modulate resting-state functional connectivity (FC) in PD and secondarily explored whether whole-brain radiomic features derived from T1-weighted and fractional anisotropy (FA) images could detect pre–post differences over this short intervention interval. Fifty patients with idiopathic PD were randomized to QMT or a SHAM repetitive stepping condition, and 48 completed the protocol (25 SHAM, 23 QMT). MRI was acquired at baseline and after 4 weeks and included resting-state fMRI, 3D T1-weighted imaging, and diffusion-derived FA maps. Resting-state fMRI was analyzed using independent component analysis and dual regression, whereas an IBSI-compliant radiomics workflow and machine-learning models were used for exploratory scan-level classification. Compared with baseline, the SHAM group showed reduced synchronization across several resting-state networks, whereas the QMT group showed increased synchronization in the right sensorimotor and frontoparietal networks and no significant reductions. Between-group analyses showed lower delta-FC in SHAM than QMT in the cerebellar and sensorimotor networks. In contrast, radiomics showed limited discrimination between pre- and post-QMT scans; the best model achieved a ROC-AUC of 0.65 with near-chance accuracy, and no selected predictor remained significant after multiple-comparison correction. These findings suggest that QMT may support short-term functional network stability or task-relevant reorganization in PD relative to the SHAM condition, whereas whole-brain structural radiomics appears less sensitive for detecting early training-related effects in this setting.