Griet Vervoort1, Kaat Alaerts2, Aniek Bengevoord3, Evelien Nackaerts4, Elke Heremans5, Wim Vandenberghe6, Alice Nieuwboer7. 1. KU Leuven, Department of Rehabilitation Sciences, Tervuursevest 101/1501, 3001 Leuven, Belgium. Electronic address: griet.vervoort@faber.kuleuven.be. 2. KU Leuven, Department of Rehabilitation Sciences, Tervuursevest 101/1501, 3001 Leuven, Belgium. Electronic address: kaat.alaerts@faber.kuleuven.be. 3. KU Leuven, Department of Rehabilitation Sciences, Tervuursevest 101/1501, 3001 Leuven, Belgium. Electronic address: aniek.bengevoord@faber.kuleuven.be. 4. KU Leuven, Department of Rehabilitation Sciences, Tervuursevest 101/1501, 3001 Leuven, Belgium. Electronic address: evelien.nackaerts@faber.kuleuven.be. 5. KU Leuven, Department of Rehabilitation Sciences, Tervuursevest 101/1501, 3001 Leuven, Belgium. Electronic address: elke.heremans@faber.kuleuven.be. 6. University Hospitals Leuven, Department of Neurology, Herestraat 49, 3000 Leuven, Belgium. Electronic address: wim.vandenberghe@uzleuven.be. 7. KU Leuven, Department of Rehabilitation Sciences, Tervuursevest 101/1501, 3001 Leuven, Belgium. Electronic address: alice.nieuwboer@faber.kuleuven.be.
Abstract
BACKGROUND: Insight into the neural mechanisms of postural instability and gait disorder (PIGD) and tremor dominant (TD) subtypes in Parkinson's disease (PD) is indispensable for generating pathophysiology hypotheses underlying this phenotyping. This cross-sectional study aimed to gain insight in specific and brain-wide functional connectivity (FC) and its correlation with motor deterioration and preservation in PD subtypes. METHODS: 68 PD patients classified as PIGD (n = 41), TD (n = 19) or indeterminate (n = 8) and 19 age-matched controls underwent resting-state fMRI while 'off' medication to assess FC between regions of interest (ROIs) in the motor and fronto-parietal network and on a whole-brain level using a parcellated template. FC alterations were correlated with quantitative behavioral measures. RESULTS: ROI-analyses showed decreased FC between the caudate and putamen in PIGD compared to TD. This hypo-connectivity was correlated with behavioral impairment. In contrast, TD-specific hyper-connectivity between motor cortical areas and the inferior parietal lobule correlated with less behavioral impairment, suggesting compensatory mechanisms. Both subgroups showed hyper-connectivity between the left supplementary motor area and pedunculopontine nucleus, whereas PIGD-specific right lateralized hyper-connectivity was shown between this nucleus and the premotor cortex. Whole-brain analyses revealed 65% hypo-connectivity and 35% hyper-connectivity in PIGD compared to TD. TD also revealed primarily hypo-connectivity compared to controls, but had more pronounced hyper-connectivity involving temporo-occipital areas. CONCLUSION: This multilevel analysis showed differential connectivity alterations in large scale neural networks and between motor and cognitive control areas that related to behavioral heterogeneity in PD, underscoring the classic TD-PIGD phenotypical classification.
BACKGROUND: Insight into the neural mechanisms of postural instability and gait disorder (PIGD) and tremor dominant (TD) subtypes in Parkinson's disease (PD) is indispensable for generating pathophysiology hypotheses underlying this phenotyping. This cross-sectional study aimed to gain insight in specific and brain-wide functional connectivity (FC) and its correlation with motor deterioration and preservation in PD subtypes. METHODS: 68 PDpatients classified as PIGD (n = 41), TD (n = 19) or indeterminate (n = 8) and 19 age-matched controls underwent resting-state fMRI while 'off' medication to assess FC between regions of interest (ROIs) in the motor and fronto-parietal network and on a whole-brain level using a parcellated template. FC alterations were correlated with quantitative behavioral measures. RESULTS: ROI-analyses showed decreased FC between the caudate and putamen in PIGD compared to TD. This hypo-connectivity was correlated with behavioral impairment. In contrast, TD-specific hyper-connectivity between motor cortical areas and the inferior parietal lobule correlated with less behavioral impairment, suggesting compensatory mechanisms. Both subgroups showed hyper-connectivity between the left supplementary motor area and pedunculopontine nucleus, whereas PIGD-specific right lateralized hyper-connectivity was shown between this nucleus and the premotor cortex. Whole-brain analyses revealed 65% hypo-connectivity and 35% hyper-connectivity in PIGD compared to TD. TD also revealed primarily hypo-connectivity compared to controls, but had more pronounced hyper-connectivity involving temporo-occipital areas. CONCLUSION: This multilevel analysis showed differential connectivity alterations in large scale neural networks and between motor and cognitive control areas that related to behavioral heterogeneity in PD, underscoring the classic TD-PIGD phenotypical classification.
Authors: Caterina Gratton; Jonathan M Koller; William Shannon; Deanna J Greene; Baijayanta Maiti; Abraham Z Snyder; Steven E Petersen; Joel S Perlmutter; Meghan C Campbell Journal: Cereb Cortex Date: 2019-06-01 Impact factor: 5.357
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