Dataset Information

The cholinergic contribution to the resting-state functional network in non-demented Parkinson's disease.

ABSTRACT: The cholinergic system arising from the basal forebrain plays an important role in cognitive performance in Parkinson's disease (PD). Here, we analyzed cholinergic status-dependent cortical and subcortical resting-state functional connectivity in PD. A total of 61 drug-naïve PD patients were divided into tertiles based on normalized substantia innominata (SI) volumes. We compared the resting-state network from seed region of interest in the caudate, posterior cingulate cortex (PCC), and SI between the lowest (PD-L) and highest tertile (PD-H) groups. Correlation analysis of the functional networks was also performed in all subjects. The functional network analysis showed that PD-L subjects displayed decreased striato-cortical functional connectivity compared with PD-H subjects. Selecting the PCC as a seed, the PD-L patients displayed decreased functional connectivity compared to PD-H patients. Meanwhile, PD-L subjects had significantly increased cortical functional connectivity with the SI compared with PD-H subjects. Correlation analysis revealed that SI volume had a positive correlation with functional connectivity from the right caudate and PCC. The present study demonstrated that PD patients exhibited unique functional connectivity from the caudate and the PCC that may be closely associated with cholinergic status, suggesting an important role for the cholinergic system in PD-associated cognition.

SUBMITTER: Lee Y

PROVIDER: S-EPMC5955917 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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The cholinergic contribution to the resting-state functional network in non-demented Parkinson's disease.

Lee Yoonju Y Ham Jee Hyun JH Cha Jungho J Park Yeong-Hun YH Lee Jae Jung JJ Sunwoo Mun Kyung MK Hong Jin Yong JY Sohn Young H YH Lee Jong-Min JM Lee Phil Hyu PH

Scientific reports 20180516 1

The cholinergic system arising from the basal forebrain plays an important role in cognitive performance in Parkinson's disease (PD). Here, we analyzed cholinergic status-dependent cortical and subcortical resting-state functional connectivity in PD. A total of 61 drug-naïve PD patients were divided into tertiles based on normalized substantia innominata (SI) volumes. We compared the resting-state network from seed region of interest in the caudate, posterior cingulate cortex (PCC), and SI betwe ...[more]

PMID: 29769626

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Project description:OBJECTIVE:Evaluation of a data-driven, model-based classification approach to discriminate idiopathic Parkinson's disease (PD) patients from healthy controls (HC) based on between-network connectivity in whole-brain resting-state functional MRI (rs-fMRI). METHODS:Whole-brain rs-fMRI (EPI, TR = 2.2?s, TE = 30?ms, flip angle = 90°. resolution = 3.1 × 3.1 × 3.1?mm, acquisition time ? 11?min) was assessed in 42 PD patients (medical OFF) and 47 HC matched for age and gender. Between-network connectivity based on full and L2-regularized partial correlation measures were computed for each subject based on canonical functional network architectures of two cohorts at different levels of granularity (Human Connectome Project: 15/25/50/100/200 networks; 1000BRAINS: 15/25/50/70 networks). A Boosted Logistic Regression model was trained on the correlation matrices using a nested cross-validation (CV) with 10 outer and 10 inner folds for an unbiased performance estimate, treating the canonical functional network architecture and the type of correlation as hyperparameters. The number of boosting iterations was fixed at 100. The model with the highest mean accuracy over the inner folds was trained using an non-nested 10-fold 20-repeats CV over the whole dataset to determine feature importance. RESULTS:Over the outer folds the mean accuracy was found to be 76.2% (median 77.8%, SD 18.2, IQR 69.4 - 87.1%). Mean sensitivity was 81% (median 80%, SD 21.1, IQR 75 - 100%) and mean specificity was 72.7% (median 75%, SD 20.4, IQR 66.7 - 80%). The 1000BRAINS 50-network-parcellation, using full correlations, performed best over the inner folds. The top features predominantly included sensorimotor as well as sensory networks. CONCLUSION:A rs-fMRI whole-brain-connectivity, data-driven, model-based approach to discriminate PD patients from healthy controls shows a very good accuracy and a high sensitivity. Given the high sensitivity of the approach, it may be of use in a screening setting. ADVANCES IN KNOWLEDGE:Resting-state functional MRI could prove to be a valuable, non-invasive neuroimaging biomarker for neurodegenerative diseases. The current model-based, data-driven approach on whole-brain between-network connectivity to discriminate Parkinson's disease patients from healthy controls shows promising results with a very good accuracy and a very high sensitivity.

Project description:Deep convolutional neural network (DCNN) provides a multivariate framework to detect relevant spatio-oscillatory patterns in the data beyond common mass-univariate statistics. Yet, its practical application is limited due to the low interpretability of the results beyond accuracy. We opted to use DCNN with a minimalistic architecture design and large penalized terms to yield a generalizable and clinically relevant network model. Our network was trained based on the scalp topology of the electroencephalography (EEG) from an open access dataset, constituting our primary sample of healthy controls (n = 25) and Parkinson's disease (PD) patients (n = 25), with and without medication. Next, we validated the model on another independent, yet comparable open access EEG dataset (healthy controls (n = 20) and PD patients (n = 20)), which was unseen to the network. We applied Gradient-weighted Class Activation Mapping (Grad-CAM) interpretability technique to create a localization map exhibiting the key network predictors, based on the gradients of the classification score flowing into the last convolutional layer. Accordingly, our results indicated that a sub-second of intrinsic oscillatory power pattern in the beta band over the occipitoparietal, gamma band over the left motor cortex as well as theta band over the frontoparietal cluster, had the largest impact on the network score for dissociating the PD patients from age- and gender-matched healthy controls, across the two datasets. We further found that the off-medication motor symptoms were related to the occipitoparietal off-medication beta power whereas the disease duration was associated with the off-medication beta power of the motor cortex. The on-medication theta power of the frontoparietal was related to the improvement of the motor symptoms. In conclusion, our method enabled us to characterize PD patho-electrophysiology according to the multivariate topographic analysis approach, where both spatial and frequency aspects of the oscillations were simultaneously considered. Moreover, our approach was free from common reference problem of the EEG data analyses.

Dataset Information

The cholinergic contribution to the resting-state functional network in non-demented Parkinson's disease.

Publications

The cholinergic contribution to the resting-state functional network in non-demented Parkinson's disease.

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