Cerebellar functional connectivity change is associated with motor and neuropsychological function in early stage drug-naïve patients with Parkinson’s disease

Abstract

IntroductionParkinson’s Disease (PD) is a progressive neurodegenerative disorder affecting both motor and cognitive function. Previous neuroimaging studies have reported altered functional connectivity (FC) in distributed functional networks. However, most neuroimaging studies focused on patients at an advanced stage and with antiparkinsonian medication. This study aims to conduct a cross-sectional study on cerebellar FC changes in early-stage drug-naïve PD patients and its association with motor and cognitive function.MethodsTwenty-nine early-stage drug-naïve PD patients and 20 healthy controls (HCs) with resting-state fMRI data and motor UPDRS and neuropsychological cognitive data were extracted from the Parkinson’s Progression Markers Initiative (PPMI) archives. We used seed-based resting-state fMRI (rs-fMRI) FC analysis and the cerebellar seeds were defined based on the hierarchical parcellation of the cerebellum (AAL atlas) and its topological function mapping (motor cerebellum and non-motor cerebellum).ResultsThe early stage drug-naïve PD patients had significant differences in cerebellar FC when compared with HCs. Our findings include: (1) Increased intra-cerebellar FC within motor cerebellum, (2) increase motor cerebellar FC in inferior temporal gyrus and lateral occipital gyrus within ventral visual pathway and decreased motor-cerebellar FC in cuneus and dorsal posterior precuneus within dorsal visual pathway, (3) increased non-motor cerebellar FC in attention, language, and visual cortical networks, (4) increased vermal FC in somatomotor cortical network, and (5) decreased non-motor and vermal FC within brainstem, thalamus and hippocampus. Enhanced FC within motor cerebellum is positively associated with the MDS-UPDRS motor score and enhanced non-motor FC and vermal FC is negatively associated with cognitive function test scores of SDM and SFT.ConclusionThese findings provide support for the involvement of cerebellum at an early stage and prior to clinical presentation of non-motor features of the disease in PD patients.

Understanding the role of cerebellum in early Parkinson’s disease: a structural and functional MRI study

“…Taken together, studies on cerebellar connectivity in PD reveal that functional changes of FC connectivity of the cerebellum cannot be fully explained by the hypothesis of an initial compensatory connectivity followed by a decrease of FC as the disease progresses over time, as proposed by early task-related fMRI studies 34 – 36 . In fact, more recent resting state studies have reported both increased and decreased FC, sometimes in the same study, also depending on the considered brain areas 32 . In conclusion, the variability on FC findings in PD likely arises from differences in data analysis methodologies (e.g., seed-based, ICA, graph theory) and, from differences in the clinical features of patients studied 37 , making the results from the various studies difficult to compare.…”

“…In keeping with our results some studies reported a decreased cerebellar FC 23 , 24 . On the other hand, other authors found an increased cerebellar FC 25 – 29 , and others an increased FC with some regions and a decreased FC with others 30 – 32 . Moreover, some authors found a correlation between the increased FC connectivity and the clinical features of patients 26 – 29 the presence or not of dopaminergic treatment 31 , 33 while a decreased cerebellar FC has been related to a reduced cognitive performance 23 .…”