Dataset Information

Functional connectivity markers of depression in advanced Parkinson's disease.

ABSTRACT:

Background

Depression is a common comorbid condition in Parkinson's disease and a major contributor to poor quality of life. Despite this, depression in PD is under-diagnosed due to overlapping symptoms and difficulties in the assessment of depression in cognitively impaired old patients.

Objectives

This study is to explore functional connectivity markers of depression in PD patients using resting-state fMRI and help diagnose whether patients have depression or not.

Methods

We reviewed 156 advanced PD patients (duration > 5 years; 59 depressed ones) and 45 healthy control subjects who underwent a resting-state fMRI scanning. Functional connectivity analysis was employed to characterize intrinsic connectivity networks using group independent component analysis and extract connectivity features. Features were put into an all-relevant feature selection procedure within cross-validation loops, to identify features with significant discriminative power for classification. Random forest classifiers were built for depression diagnosis, on the basis of identified features.

Results

42 intrinsic connectivity networks were identified and arranged into subcortical, auditory, somatomotor, visual, cognitive control, default-mode and cerebellar networks. Six features were significantly relevant to classification. They were connectivity within posterior cingulate cortex, within insula, between posterior cingulate cortex and insula/hippocampus+amygdala, between insula and precuneus, and between superior parietal lobule and medial prefrontal cortex. The mean accuracy achieved with classifiers to discriminate depressed patients from the non-depressed was 82.4%.

Conclusions

Our findings provide preliminary evidence that resting-state functional connectivity can characterize depressed PD patients and help distinguish them from non-depressed ones.

SUBMITTER: Lin H

PROVIDER: S-EPMC6931212 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Functional connectivity markers of depression in advanced Parkinson's disease.

Lin Hai H Cai Xiaodong X Zhang Doudou D Liu Jiali J Na Peng P Li Weiping W

NeuroImage. Clinical 20191213

<h4>Background</h4>Depression is a common comorbid condition in Parkinson's disease and a major contributor to poor quality of life. Despite this, depression in PD is under-diagnosed due to overlapping symptoms and difficulties in the assessment of depression in cognitively impaired old patients.<h4>Objectives</h4>This study is to explore functional connectivity markers of depression in PD patients using resting-state fMRI and help diagnose whether patients have depression or not.<h4>Methods</h4 ...[more]

PMID: 31869768

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Project description:IntroductionThe current diagnosis of Parkinson's disease (PD) comorbidity with depression (DPD) largely depends on clinical evaluation. However, the modality may tend to lack precision in detecting PD with depression. A radiomic approach that combines functional connectivity and activity with clinical scores has the potential to achieve accurate and differential diagnosis between PD and DPD.MethodsIn this study, we aimed to employ the radiomic approach to extract large-scale features of functional connectivity and activity for differentiating among DPD, PD with no depression (NDPD), and healthy controls (HC). We extracted 6,557 features of five types from all subjects including clinical characteristics, resting-state functional connectivity (RSFC), amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and voxel-mirrored homotopic connectivity (VMHC). Lasso, random forest, and support vector machine (SVM) were implemented for feature selection and dimension reduction based on the training sets, and the prediction performance for different methods in the testing sets was compared.ResultsThe results showed that nineteen features were selected for the group of DPD versus HC, 34 features were selected for the group of NDPD versus HC, and 17 features were retained for the group of DPD versus NDPD. In the testing sets, Lasso prediction achieved the accuracies of 0.95, 0.96, and 0.85 for distinguishing between DPD and HC, NDPD and HC, and DPD and NDPD, respectively. Random forest achieved the accuracies of 0.90, 0.82, and 0.90 for distinguishing between DPD and HC, NDPD and HC, and DPD and NDPD, respectively, while SVM yielded the accuracies of 1, 0.86 and 0.65 for distinguishing between DPD and HC, NDPD and HC, and DPD and NDPD, respectively.ConclusionsBy identifying aberrant functional connectivity and activity as potential biomarkers, the radiomic approach facilitates a deeper understanding and provides new insights into the pathophysiology of DPD to support the clinical diagnosis with high prediction accuracy.

Project description:Since anatomic MRI is presently not able to directly discern neuronal loss in Parkinson's Disease (PD), studying the associated functional connectivity (FC) changes seems a promising approach toward developing non-invasive and non-radioactive neuroimaging markers for this disease. While several groups have reported such FC changes in PD, there are also significant discrepancies between studies. Investigating the reproducibility of PD-related FC changes on independent datasets is therefore of crucial importance. We acquired resting-state fMRI scans for 43 subjects (27 patients and 16 normal controls, with 2 replicate scans per subject) and compared the observed FC changes with those obtained in two independent datasets, one made available by the PPMI consortium (91 patients, 18 controls) and a second one by the group of Tao Wu (20 patients, 20 controls). Unfortunately, PD-related functional connectivity changes turned out to be non-reproducible across datasets. This could be due to disease heterogeneity, but also to technical differences. To distinguish between the two, we devised a method to directly check for disease heterogeneity using random splits of a single dataset. Since we still observe non-reproducibility in a large fraction of random splits of the same dataset, we conclude that functional heterogeneity may be a dominating factor behind the lack of reproducibility of FC alterations in different rs-fMRI studies of PD. While global PD-related functional connectivity changes were non-reproducible across datasets, we identified a few individual brain region pairs with marginally consistent FC changes across all three datasets. However, training classifiers on each one of the three datasets to discriminate PD scans from controls produced only low accuracies on the remaining two test datasets. Moreover, classifiers trained and tested on random splits of the same dataset (which are technically homogeneous) also had low test accuracies, directly substantiating disease heterogeneity.

Project description:Dynamic functional connectivity captures temporal variations of functional connectivity during MRI acquisition and it may be a suitable method to detect cognitive changes in Parkinson's disease. In this study, we evaluated 118 patients with Parkinson's disease matched for age, sex and education with 35 healthy control subjects. Patients with Parkinson's disease were classified with normal cognition (n = 52), mild cognitive impairment (n = 46), and dementia (n = 20) based on an extensive neuropsychological evaluation. Resting state functional MRI and a sliding-window approach were used to study the dynamic functional connectivity. Dynamic analysis suggested two distinct connectivity 'States' across the entire group: a more frequent, segregated brain state characterized by the predominance of within-network connections, State I, and a less frequent, integrated state with strongly connected functional internetwork components, State II. In Parkinson's disease, State I occurred 13.89% more often than in healthy control subjects, paralleled by a proportional reduction of State II. Parkinson's disease subgroups analyses showed the segregated state occurred more frequently in Parkinson's disease dementia than in mild cognitive impairment and normal cognition groups. Further, patients with Parkinson's disease dementia dwelled significantly longer in the segregated State I, and showed a significant lower number of transitions to the strongly interconnected State II compared to the other subgroups. Our study indicates that dementia in Parkinson's disease is characterized by altered temporal properties in dynamic connectivity. In addition, our results show that increased dwell time in the segregated state and reduced number of transitions between states are associated with presence of dementia in Parkinson's disease. Further studies on dynamic functional connectivity changes could help to better understand the progressive dysfunction of networks between Parkinson's disease cognitive states.

Dataset Information

Functional connectivity markers of depression in advanced Parkinson's disease.

Background

Objectives

Methods

Results

Conclusions

Publications

Functional connectivity markers of depression in advanced Parkinson's disease.

Similar Datasets

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