Dataset Information

Cortical Structural Connectivity Alterations and Potential Pathogenesis in Mid-Stage Sporadic Parkinson's Disease.

ABSTRACT: Many clinical symptoms of sporadic Parkinson's disease (sPD) cannot be completely explained by a lesion of the simple typical extrapyramidal circuit between the striatum and substantia nigra. Therefore, this study aimed to explore the new potential damaged pathogenesis of other brain regions associated with the multiple and complex clinical symptoms of sPD through magnetic resonance imaging (MRI). A total of 65 patients with mid-stage sPD and 35 healthy controls were recruited in this study. Cortical structural connectivity was assessed by seed-based analysis using the vertex-based morphology of MRI. Seven different clusters in the brain regions of cortical thickness thinning derived from the regression analysis using brain size as covariates between sPD and control were selected as seeds. Results showed that the significant alteration of cortical structural connectivity mainly occurred in the bilateral frontal orbital, opercular, triangular, precentral, rectus, supplementary-motor, temporal pole, angular, Heschl, parietal, supramarginal, postcentral, precuneus, occipital, lingual, cuneus, Rolandic-opercular, cingulum, parahippocampal, calcarine, olfactory, insula, paracentral-lobule, and fusiform regions at the mid-stage of sPD. These findings suggested that the extensive alteration of cortical structural connectivity is one of possible pathogenesis resulting in the multiple and complex clinical symptoms in sPD.

SUBMITTER: Deng X

PROVIDER: S-EPMC8200851 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Cortical Structural Connectivity Alterations and Potential Pathogenesis in Mid-Stage Sporadic Parkinson's Disease.

Deng Xia X Liu Zheng Z Kang Qin Q Lu Lin L Zhu Yu Y Xu Renshi R

Frontiers in aging neuroscience 20210531

Many clinical symptoms of sporadic Parkinson's disease (sPD) cannot be completely explained by a lesion of the simple typical extrapyramidal circuit between the striatum and substantia nigra. Therefore, this study aimed to explore the new potential damaged pathogenesis of other brain regions associated with the multiple and complex clinical symptoms of sPD through magnetic resonance imaging (MRI). A total of 65 patients with mid-stage sPD and 35 healthy controls were recruited in this study. Cor ...[more]

PMID: 34135748

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Project description:Context: Cognitive impairments are common in patients with Parkinson's disease (PD) and are heterogeneous in their presentation. The "dual syndrome hypothesis" suggests the existence of two distinct subtypes of mild cognitive impairment (MCI) in PD: a frontostriatal subtype with predominant attentional and/or executive deficits and a posterior cortical subtype with predominant visuospatial, memory, and/or language deficits. The latter subtype has been associated with a higher risk of developing dementia. Objective: The objective of this study was to identify structural modifications in cortical and subcortical regions associated with each PD-MCI subtype. Methods: One-hundred and fourteen non-demented PD patients underwent a comprehensive neuropsychological assessment as well as a 3T magnetic resonance imaging scan. Patients were categorized as having no cognitive impairment (n = 41) or as having a frontostriatal (n = 16), posterior cortical (n = 25), or a mixed (n = 32) MCI subtype. Cortical regions were analyzed using a surface-based Cortical thickness (CTh) method. In addition, the volumes, shapes, and textures of the caudate nuclei, hippocampi, and thalami were studied. Tractometric analyses were performed on associative and commissural white matter (WM) tracts. Results: There were no between-group differences in volumetric measurements and cortical thickness. Shape analyses revealed more abundant and more extensive deformations fields in the caudate nuclei, hippocampi, and thalami in patients with posterior cortical deficits compared to patients with no cognitive impairment. Decreased fractional anisotropy (FA) and increased mean diffusivity (MD) were also observed in the superior longitudinal fascicle, the inferior fronto-occipital fascicle, the striato-parietal tract, and the anterior and posterior commissural tracts. Texture analyses showed a significant difference in the right hippocampus of patients with a mixed MCI subtype. Conclusion: PD-MCI patients with posterior cortical deficits have more abundant and more extensive structural alterations independently of age, disease duration, and severity, which may explain why they have an increased risk of dementia.

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.

Dataset Information

Cortical Structural Connectivity Alterations and Potential Pathogenesis in Mid-Stage Sporadic Parkinson's Disease.

Publications

Cortical Structural Connectivity Alterations and Potential Pathogenesis in Mid-Stage Sporadic Parkinson's Disease.

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