Cerebellar resting-state functional connectivity in Parkinson's disease and multiple system atrophy: Characterization of abnormalities and potential for differential diagnosis at the single-patient level.

Recent studies using resting-state functional connectivity and machine-learning to distinguish patients with neurodegenerative diseases from other groups of subjects show promising results. This approach has not been tested to discriminate between Parkinson's disease (PD) and multiple system atrophy (MSA) patients. Our first aim is to characterize possible abnormalities in resting-state functional connectivity between the cerebellum and a set of intrinsic-connectivity brain networks and between the cerebellum and different regions of the striatum in PD and MSA. The second objective of this study is to assess the potential of cerebellar connectivity measures to distinguish between PD and MSA patients at the single-patient level. Fifty-nine healthy controls, 62 PD patients, and 30 MSA patients underwent resting-state functional MRI with a 3T scanner. Independent component analysis and dual regression were used to define seven resting-state networks of interest. To assess striatal connectivity, a seed-to-voxel approach was used after dividing the striatum into six regions bilaterally. Measures of cerebellar-brain network and cerebellar-striatal connectivity were then used as features in a support vector machine to discriminate between PD and MSA patients. MSA patients displayed reduced cerebellar connectivity with different brain networks and with the striatum compared with PD patients and with controls. The classification procedure achieved an overall accuracy of 77.17% with 83.33% of the MSA subjects and 74.19% of the PD patients correctly classified. Our findings suggest that measures of cerebellar functional connectivity have the potential to distinguish between PD and MSA patients.

Baggio HC ，Abos A ，Segura B ，Campabadal A ，Uribe C ，Giraldo DM ，Perez-Soriano A ，Muñoz E ，Compta Y ，Junque C ，Marti MJ ... -  《NeuroImage-Clinical》

Differences in the intra-cerebellar connections and graph theoretical measures between Parkinson's disease and multiple system atrophy.

Parkinson's disease (PD) does not present with motor symptoms until dopaminergic neuronal loss exceeds 50%. This might indicate that a network-level compensatory mechanism involving surviving regions in PD acts to reduce brain abnormalities. In contrast, there is no evidence of a compensatory mechanism in multiple system atrophy (MSA). We hypothesized that a comparison of these two diseases would help to identify compensatory effects in PD. We recruited 23 patients with PD, 11 patients with MSA, and 11 controls that showed an aging brain but no neurological deficits. All subjects underwent resting state functional magnetic resonance imaging (fMRI). Regions of interest were defined according to the motor network related to the basal ganglia and cerebellum. Network-level analyses were performed. Network-based statistical analyses revealed that functional connectivity in PD brains was reduced between cerebellar lobules IX on both sides and vermis X, as compared with MSA brains. Transitivity was reduced in MSA as compared with controls. We demonstrated that a part of the intra-cerebellar connectivity was reduced in PD, and that network segregation was reduced in MSA. However, there was no evidence of compensatory effects in PD.

Sako W ，Abe T ，Furukawa T ，Oki R ，Haji S ，Murakami N ，Izumi Y ，Harada M ，Kaji R ... -  《-》

Similarities and differences in cerebellar grey matter volume and disrupted functional connectivity in idiopathic Parkinson's disease and multiple system atrophy.

This study investigated the potential differences in changes to cerebellar grey matter volume (GMV) and functional connectivity (FC) and the association between them, which might elucidate cerebellar function in multiple system atrophy (MSA) and idiopathic Parkinson's disease (IPD). Resting-state functional magnetic resonance imaging and three-dimensional T1 scans were obtained from 38 IPD, 62 MSA, and 59 healthy controls (HC). Seed-based connectivity analysis and voxel-based morphometry analysis were performed to assess the changes of cerebellar FC and GMV between the patient groups. Decreased cerebellar GMV was found in the motor cerebellum in both patient groups relative to HC, and broader reduction of GMV was observed in both cognitive and motor cerebellum in MSA compared with IPD and HC. Compared with IPD, the MSA group exhibited decreased FC between bilateral dentate nucleus (DN) and default mode network (DMN). Decreased intracerebellar FC was observed in both patient groups relative to HC. Cerebellar GMV was positively correlated with FC of intracerebellum and DN-DMN in MSA. Motor/cognitive scores were associated with DN-DMN FC, with considerable cerebellar GMV loss in MSA patients. Cerebellar GMV loss and cerebellar FC alterations showed similarities in IPD and MSA, along with more widespread changes to GMV in motor and cognitive cerebellum and altered DN-DMN FC in MSA. Further research is needed to better describe the alterations of cerebellar GMV in the cognitive cerebellum and association between cerebellar GMV and intracerebellar FC during the early stages of MSA and IPD.

Wang N ，Zhang L ，Yang H ，Liu H ，Luo X ，Fan G ... -  《-》

Comparing abnormalities of amplitude of low-frequency fluctuations in multiple system atrophy and idiopathic Parkinson's disease measured with resting-state fMRI.

Multiple system atrophy (MSA) and Idiopathic Parkinson's disease (IPD) show overlapping clinical manifestations with different treatment and prognosis. However, the shared and distinct underlying neural substrates are not yet understood, which needs to be explored between MSA and IPD. Resting-state functional magnetic resonance imaging data were collected from 29 MSA patients, 17 IPD patients and 25 healthy controls (HC) and the Amplitude of Low-Frequency Fluctuations (ALFF) was compared. Lower ALFF in bilateral basal ganglion, bilateral ventrolateral prefrontal cortex and right amygdala, as well as higher ALFF in parieto-temporo-occipital cortex and right cerebellum was shared between both patient groups to compare with HC. In contrast to IPD, decreased or increased ALFF in different regions of visual associative cortices and decreased ALFF in right cerebellum were found in MSA group. Our findings suggested shared and distinct spontaneous brain activity abnormalities in striato-thalamo-cortical (STC) loop, default mood network, visual associative cortices and cerebellum were present in MSA and IPD, which may help to explain similar clinical symptoms in both disorders but a more severe illness prognosis in MSA. Further research is needed to better describe the functional role of the cerebellum and visual associative cortices in early stages of MSA and IPD.

Wang N ，Edmiston EK ，Luo X ，Yang H ，Chang M ，Wang F ，Fan G ... -  《-》

Functional connectome automatically differentiates multiple system atrophy (parkinsonian type) from idiopathic Parkinson's disease at early stages.

Differentiating the parkinsonian variant of multiple system atrophy (MSA-P) from idiopathic Parkinson's disease (IPD) is challenging, especially in the early stages. This study aimed to investigate differences and similarities in the brain functional connectomes of IPD and MSA-P patients and use machine learning methods to explore the diagnostic utility of these features. Resting-state fMRI data were acquired from 88 healthy controls, 76 MSA-P patients, and 53 IPD patients using a 3.0 T scanner. The whole-brain functional connectome was constructed by thresholding the Pearson correlation matrices of 116 regions, and topological properties were evaluated through graph theory approaches. Connectome measurements were used as features in machine learning models (random forest [RF]/logistic regression [LR]/support vector machine) to distinguish IPD and MSA-P patients. Regarding graph metrics, early IPD and MSA-P patients shared network topological properties. Both patient groups showed functional connectivity disruptions within the cerebellum-basal ganglia-cortical network, but these disconnections were mainly in the cortico-thalamo-cerebellar circuits in MSA-P patients and the basal ganglia-thalamo-cortical circuits in IPD patients. Among the connectome parameters, t tests combined with the RF method identified 15 features, from which the LR classifier achieved the best diagnostic performance on the validation set (accuracy = 92.31%, sensitivity = 90.91%, specificity = 93.33%, area under the receiver operating characteristic curve = 0.89). MSA-P and IPD patients show similar whole-brain network topological alterations. MSA-P primarily affects cerebellar nodes, and IPD primarily affects basal ganglia nodes; both conditions disrupt the cerebellum-basal ganglia-cortical network. Moreover, functional connectome parameters showed outstanding value in the differential diagnosis of early MSA-P and IPD.

Chen B ，Cui W ，Wang S ，Sun A ，Yu H ，Liu Y ，He J ，Fan G ... -  《-》