Abnormal dynamic functional connectivity changes correlated with non-motor symptoms of Parkinson’s disease

Abstract

BackgroundNon-motor symptoms are common in Parkinson’s disease (PD) patients, decreasing quality of life and having no specific treatments. This research investigates dynamic functional connectivity (FC) changes during PD duration and its correlations with non-motor symptoms.MethodsTwenty PD patients and 19 healthy controls (HC) from PPMI dataset were collected and used in this study. Independent component analysis (ICA) was performed to select significant components from the entire brain. Components were grouped into seven resting-state intrinsic networks. Static and dynamic FC changes during resting-state functional magnetic resonance imaging (fMRI) were calculated based on selected components and resting state networks (RSN).ResultsStatic FC analysis results showed that there was no difference between PD-baseline (PD-BL) and HC group. Network averaged connection between frontoparietal network and sensorimotor network (SMN) of PD-follow up (PD-FU) was lower than PD-BL. Dynamic FC analysis results suggested four distinct states, and each state’s temporal characteristics, such as fractional windows and mean dwell time, were calculated. The state 2 of our study showed positive coupling within and between SMN and visual network, while the state 3 showed hypo-coupling through all RSN. The fractional windows and mean dwell time of PD-FU state 2 (positive coupling state) were statistically lower than PD-BL. Fractional windows and mean dwell time of PD-FU state 3 (hypo-coupling state) were statistically higher than PD-BL. Outcome scales in Parkinson’s disease–autonomic dysfunction scores of PD-FU positively correlated with mean dwell time of state 3 of PD-FU.ConclusionOverall, our finding indicated that PD-FU patients spent more time in hypo-coupling state than PD-BL. The increase of hypo-coupling state and decrease of positive coupling state might correlate with the worsening of non-motor symptoms in PD patients. Dynamic FC analysis of resting-state fMRI can be used as monitoring tool for PD progression.

Brain Dynamics Complexity as a Signature of Cognitive Decline in Parkinson's Disease

“…We demonstrated that PD is characterized by altered temporal properties in dynamic connectivity, with a longer dwell time in segregated states and a reduced number of transitions to the more integrated states, leading to increased local segregation and reduced “crosstalk” between brain networks, particularly in PDD 6 . Other studies have now confirmed our initial findings, 44 including a 5‐year longitudinal study reporting increased functional brain disconnectivity with PD progression, that strongly correlated with global cognitive deterioration 45 …”

“…6 We demonstrated that PD is characterized by altered temporal properties in dynamic connectivity, with a longer dwell time in segregated states and a reduced number of transitions to the more integrated states, leading to increased local segregation and reduced "crosstalk" between brain networks, particularly in PDD. 6 Other studies have now confirmed our initial findings, 44 including a 5-year longitudinal study reporting increased functional brain disconnectivity with PD progression, that strongly correlated with global cognitive deterioration. 45 Here, in line with these observations, PD-subgroup analyses show that the CEN and DMN neural dynamic complexity is strongly linked to cognitive status, because PDD presented a significant higher complexity in specific ICs-IC48 (CEN) and IC34 (DMN)-than PD-NC and PD-MCI, as well as in IC45 (DMN) compared to PD-NC, possibly suggesting an increased local segregation in these nodes associated with a more severe cognitive state.…”

Dynamic properties in functional connectivity changes and striatal dopamine deficiency in Parkinson’s disease

“…Together with our previous results indicating that dynamic transitions between states of global integration and segregation are impaired in PD, these results extend the notion that PD patients may have problems transitioning specifically into a state of global integration. Interestingly, another study longitudinally investigating dFC changes in PPMI data revealed a decrease in dwell time in a state similar to the GI state and an increase in dwell time for a state corresponding to the lesser connected state(Cao et al, 2023). Their results suggest that hypocoupling worsens in the course of PD (Cao et al, 2023).…”

“…In PD, several recent whole-brain dFC accounts suggested the relevance of network dynamics in the clinical presentation of PD (Cao et al, 2023; Cordes et al, 2018; Díez-Cirarda et al, 2018; Fiorenzato et al, 2019; Kim et al, 2017). Importantly, these studies could show that PD-specific changes in dFC were linked to motor symptom severity (Kim et al, 2017), mild cognitive impairment (MCI) (Díez-Cirarda et al, 2018; Fiorenzato et al, 2019), PD dementia (PDD) (Fiorenzato et al, 2019), and autonomic dysfunction (Cao et al, 2023). Together, these studies emphasize that motor and cognitive impairments in PD appear to be driven by spatial and temporal alterations of large-scale network dynamics.…”

“…However, reports from PD are inconsistent. While some studies suggested PD to be associated with a higher occurrence of highly interconnected states (i.e., reoccurring patterns of functional connectivity across time) (Díez-Cirarda et al, 2018; Kim et al, 2017), others demonstrated PD (Fiorenzato et al, 2019) and PD progression (Cao et al, 2023) to be associated with a higher occurrence of sparsely connected states. These inconsistent findings, however, may be due to methodological differences in data analyses and study design.…”