Background. Nigrostriatal dopaminergic loss is a hallmark of Parkinson's disease (PD) pathophysiology, leading to motor Parkinsonism. Different intervention protocols have shown that motor and cognitive functions improvement in PD occur via the modulation of distinct motor and cognitive pathways. Objective. To investigate the effects of two motor training programs on the brains' functional networks in PD patients. Methods. Thirty-seven PD patients were prospectively studied. All enrolled patients underwent either treadmill training (TT) (n = 19) or treadmill with virtual reality (TT + VR) (n = 18) for 6 weeks. Magnetic resonance imaging (MRI) scans (3 T) acquiring 3-dimensional T1-weighted and resting-state functional MRI (rs-fMRI) data sets were performed at baseline and after 6 weeks. Independent component analysis (ICA) was conducted, and functional connectivity (FC) changes within large-scale functional brain networks were examined. Results. In both groups, significant post-training FC decrease in striatal, limbic, and parietal regions within the basal ganglia network, executive control network, and frontal-striatal network, and significant FC increase in the caudate, and cingulate within the sensorimotor network (SMN) were observed. Moreover, a significant time × group interaction was detected where TT + VR training had greater effects on FC levels in the supplementary motor area (SMA) and right precentral gyrus within the SMN, and in the right middle frontal gyrus (MFG) within the cerebellar network. These FC alterations were associated with improved usual and dual-task walking performance. Conclusions. These results suggest that TT with-and-without the addition of a VR component affects distinct neural pathways, highlighting the potential for beneficial neural plasticity in PD. Such distinctive task-specific pathways may foster the facilitation of interventions tailored to the individual needs of PD patients. Registered at Clinicaltrials.gov number: NCT01732653.
Keywords: Parkinson’s disease; gait; motor rehabilitation; resting-state functional MRI; virtual reality.