Objective: Frequent falls are common in Parkinson's disease (PD). Resting-state fMRI (rs-fMRI) studies have found differences in functional connectivity between PD patients and healthy controls. However, whether functional connectivity in PD patients with frequent falls (PD-fallers) differs from those without falls (PD-non fallers) is unknown. Therefore, to elucidate the underlying mechanisms leading to postural instability in PD patients with frequent falls, we compared changes in functional connectivity between PD-fallers, PD-non fallers and healthy controls.Methods: Thirteen healthy controls (70.7 ± 7.2 years) were compared to thirteen PD-fallers (70.6 ± 5.9 years) and 19 PD-non fallers (71.61 ± 5.8 years) without cognitive impairment. We performed 1.5T rs-fMRI scans and evaluated gait and balance, motor symptoms and cognitive functions.Results: Cerebellar seed regions showed increased functional connectivity in PD-fallers compared to controls in two connections between the cerebellar cortex and vermis (p-value = 0.02). Conversely, in comparison to controls, functional connectivity between the precuneus and caudate nucleus was decreased in PD-non fallers (p-value = 0.015). A similar trend was also observed between controls and PD-fallers, although this difference did not reach statistical significance.Discussion: We found increased functional connectivity among cerebellar structures in PD, which may reflect an adaptive (compensatory) mechanism through activation of additional brain structures to restore gait function. In contrast, a relative disconnection between the precuneus and caudate nucleus in PD patients might indicate an impaired brain network unrelated to the risk of falls. Cerebellar areas might thus be considered as future therapeutic targets for neuromodulatory treatment of postural instability in PD.Abbreviations: DMN: default mode network; FC: functional connectivity; IPL: inferior parietal lobule; MMSE: Minimal Mental Status Examination; PD: Parkinson's disease; rs-fMRI: resting-state functional Magnetic Resonance Imaging; UPDRSIII: Unified Parkinson's disease ranking scale.
Keywords: Default mode network; Parkinson’s disease; connectivity; postural instability; resting state.