Dual-task-related neural connectivity changes in patients with Parkinson’ disease

• Motor control areas involved in dual-tasking show altered functional connectivity in patients with Parkinson’s disease.
• Hyper-connectivity involving the precuneus related to worse dual-task performance in freezers.
• Hypo-connectivity within the basal ganglia points to a role for dopamine depletion in dual-task impairment in freezers.
• Other functional connectivity patterns underscore executive impairment and loss of automaticity related to freezing of gait.

Background and objectives: Dual-task (DT) gait impairment in people with Parkinson’s disease (PD) and specifically in those with freezing of gait (FOG), reflects attentional dependency of movement. This study aimed to elucidate resting-state brain connectivity alterations related to DT gait abnormalities in PD with and without FOG. Methods: PD patients (n = 73) and healthy age-matched controls (n = 20) underwent DT gait analysis and resting-state functional Magnetic Resonance Imaging (rs-MRI) while ‘off’ medication. Patients were classified as freezer (n = 13) or non-freezer (n = 60). Functional connectivity (FC) alterations between PD and controls and between patient subgroups were assessed in regions of interest (ROIs) within the fronto-parietal and motor network. Results: PD had longer stance times, shorter swing times and more step length asymmetry during DT gait and needed more time and steps during DT turning compared to controls. Additionally, freezers showed similar impairments and longer double support times compared to non-freezers during DT gait. PD demonstrated hyper-connectivity between the inferior parietal lobule and premotor cortex (PMC) and between the cerebellum and the PMC and M1. FOG-specific hypo-connectivity within the striatum and between the caudate and superior temporal lobe and hyper-connectivity between the dorsal putamen and precuneus was correlated with worse DT performance. Conclusion: PD showed FC alterations in DT-related networks, which were not correlated to DT performance. However, FOG-specific FC alterations in DT-related regions involving the precuneus and striatum were correlated to worse DT performance, suggesting that the balance between cognitive and motor networks is altered.