Altered Brain Functional Connectivity Between Tremor And Nontremor Parkinson’s Disease:A Dynamic Perspective

Background:Parkinson’s disease(PD)is highly heterogeneous in early clinical features and later outcomes.And this makes classifying subgroups of PD into tremor-dominant and nontremor-dominant.Previous studies suggest abnormal changes between two PD phenotypes in static functional connectivity by using resting-state functional magnetic resonance imaging(f MRI).However,the dynamic characteristics of brain networks between two PD phenotypes are not yet clear.Thus,we aimed to reveal dynamic functional connectivity(d FC)between the two PD phenotypes by using a variety of d FC analysis techniques.Methods:Study 1: We investigated resting state f MRI data from 29 tremor-dominant PD patients(PDTD),25 nontremor-dominant PD patients(PDNTD)and 20 healthy controls.Dynamic functional network connectivity(d FNC)was analyzed by using an independent component analysis,sliding window method,k-means clustering and graph theory analysis.We further compared d FC between different PD subtypes,and assessed the relationship between alterations in the dynamic properties and clincial feature.Study 2: 18 Parkinson’s patients with resting tremor and 6 without resting tremor participated in our study.We selected bilateral globus pallidus as seed points to analyze the d FC between the seed points and the whole brain.The variance of d FC was calculated to evaluate the temporal variability of functional connectivity between bilateral globus pallidus and the whole brain.Results:Study 1: Four different d FNC states were identified by k-means clustering algorithm,one of them showing sparse connections(state I).PDTD patients spent more time in state I and showed increased FNC between BG and v SMN in state IV relative to PDNTD patients.Both PD phenotypes exhibited higher FNC between d SMN and FPN in state II and in state III compared to the controls.PDNTD patients showed decreased FNC between BG and FPN but increased FNC in the bilateral FPN compared to both PDTD patients and controls.Additionally,there was a higher variability in the network global efficiency in PDNTD patients.Dwell time in state I and d FNC strength between BG and v SMN in state IV were positively correlated with resting tremor score and total tremor score respectively.Study 2: Compared with PDTD,the variance of d FNC between left globus pallidus and left middle frontal lobe increased in PDNTD group.Conclusion:This study showed significant differences in dynamic functional network connectivity between the PDTD and PDNTD patients,from dynamic perspective(temporal properties of FNC state,variability of network topological organization and Seed-based FC).And severity of tremor was associated with dwell time in state I and increased FNC between BG and v SMN in state IV.These findings may help better understanding neural substrates underlying different PD types and suggest that d FC may serve as a novel physiological biomarker of disease.