Karthik Sreenivasan1, Virendra Mishra1, Christopher Bird1, Xiaowei Zhuang1, Zhengshi Yang1, Dietmar Cordes2, Ryan R Walsh3. 1. Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, 89106, USA. 2. Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, 89106, USA; University of Colorado, Boulder, CO, 80309, USA. 3. Muhammad Ali Parkinson Center at Barrow Neurological Institute, Phoenix, AZ, USA. Electronic address: Ryan.Walsh@BarrowNeuro.org.
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.
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 PDpatients 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.
Authors: N Tzourio-Mazoyer; B Landeau; D Papathanassiou; F Crivello; O Etard; N Delcroix; B Mazoyer; M Joliot Journal: Neuroimage Date: 2002-01 Impact factor: 6.556
Authors: Christopher G Goetz; Barbara C Tilley; Stephanie R Shaftman; Glenn T Stebbins; Stanley Fahn; Pablo Martinez-Martin; Werner Poewe; Cristina Sampaio; Matthew B Stern; Richard Dodel; Bruno Dubois; Robert Holloway; Joseph Jankovic; Jaime Kulisevsky; Anthony E Lang; Andrew Lees; Sue Leurgans; Peter A LeWitt; David Nyenhuis; C Warren Olanow; Olivier Rascol; Anette Schrag; Jeanne A Teresi; Jacobus J van Hilten; Nancy LaPelle Journal: Mov Disord Date: 2008-11-15 Impact factor: 10.338