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Altered functional network topology correlates with clinical measures in very early-stage, drug-naïve Parkinson's disease

      Highlights

      • Altered functional network integration and segregation in PD, despite lack of prior assumptions or modeling in this study.
      • Altered network metrics correlate with clinical measures, despite using unbiased whole-brain approach in very early PD.
      • Results suggest a functional-pathology relationship between network dysfunction and manifestation of disease over time.
      • Findings are evident in a well characterized, homogeneous, multi-site cohort of very early-stage, drug naïve PD patients.

      Abstract

      Introduction

      The aim of the study was to identify abnormalities of whole-brain network functional organization and their relation to clinical measures in a well-characterized, multi-site cohort of very early-stage, drug-naïve Parkinson's Disease (PD) patients.

      Methods

      Functional-MRI data for 16 healthy controls and 20 very early-stage, drug-naïve patients with PD were obtained from the Parkinson's Progression Markers Initiative database after controlling for strict inclusion/exclusion imaging criteria. Connectivity between regions of interest was estimated using Pearson's correlation between averaged time-series, and subsequently a connectivity matrix was obtained for each subject. These connectivity matrices were then used in an unbiased, whole-brain graph theoretical approach to investigate the functional connectome and its correlation with disease severity in very early PD.

      Results

      The current study revealed altered network topology which correlated with multiple clinical measures in very early drug-naïve PD. Decreased functional segregation and integration (both globally and locally) were evident in PD. Importantly, our results demonstrated that most of the cortical regions hypothesized to be involved early in PD manifested decreased graph theoretical measures, despite utilizing a whole-brain analytic approach that is free from prior assumptions regarding cortical region involvement.

      Conclusion

      Graph theoretical investigation of very early drug-naïve PD revealed disrupted topological organization. These findings are evident in a stringently homogeneous group of very early-stage, medication-naive, and non-tremor dominant PD patients by using a whole-brain unbiased approach. These results provide an important unbiased and rigorously controlled baseline for understanding further studies of PD functional connectivity investigating response to treatment, symptom development, and disease progression.

      Keywords

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