Elevated caudate connectivity in cognitively normal Parkinson’s disease patients

Wright, Natalie; Alhindi, Abrar; Millikin, Colleen; Modirrousta, Mandana; Udow, Sean; Borys, Andrew; Anang, Julius; Hobson, Douglas E.; Ko, Ji Hyun

doi:10.1038/s41598-020-75008-6

Cited by 17 publications

(12 citation statements)

References 63 publications

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“…In agreement with these PET and rs-fMRI observations, previous rs-fMRI studies were likewise indicative of an anterior-posterior gradient and therefore of striatal dysconnectivity to different areas 38 . Furthermore, we found further evidence for a potentially compensatory role 42 of the caudate in earlier disease stages, as the seed in which a significant dopaminergic deficit was observed at follow-up compared to baseline, exhibited an increased FC to a cluster in the iLOCl, which showed a high spatial correspondence with the corresponding dysconnectivity of the same seed observed when comparing both visits.…”

Section: Discussionsupporting

confidence: 61%

Longitudinal trimodal imaging of midbrain-associated network degeneration in Parkinson’s disease

Steidel

Ruppert

Greuel

et al. 2022

npj Parkinsons Dis.

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The prevailing network perspective of Parkinson’s disease (PD) emerges not least from the ascending neuropathology traceable in histological studies. However, whether longitudinal in vivo correlates of network degeneration in PD can be observed remains unresolved. Here, we applied a trimodal imaging protocol combining 18F-fluorodeoxyglucose (FDG)- and 18F-fluoro-L-Dopa- (FDOPA)-PET with resting-state functional MRI to assess longitudinal changes in midbrain metabolism, striatal dopamine depletion and striatocortical dysconnectivity in 17 well-characterized PD patients. Whole-brain (un)paired-t-tests with focus on midbrain or striatum were performed between visits and in relation to 14 healthy controls (HC) in PET modalities. Resulting clusters of FDOPA-PET comparisons provided volumes for seed-based functional connectivity (FC) analyses between visits and in relation to HC. FDG metabolism in the left midbrain decreased compared to baseline along with caudatal FDOPA-uptake. This caudate cluster exhibited a longitudinal FC decrease to sensorimotor and frontal areas. Compared to healthy subjects, dopamine-depleted putamina indicated stronger decline in striatocortical FC at follow-up with respect to baseline. Increasing nigrostriatal deficits and striatocortical decoupling were associated with deterioration in motor scores between visits in repeated-measures correlations. In summary, our results demonstrate the feasibility of in-vivo tracking of progressive network degeneration using a multimodal imaging approach. Specifically, our data suggest advancing striatal and widespread striatocortical dysfunction via an anterior-posterior gradient originating from a hypometabolic midbrain cluster within a well-characterized and only mild to moderately affected PD cohort during a relatively short period.

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Section: Discussionsupporting

confidence: 61%

Longitudinal trimodal imaging of midbrain-associated network degeneration in Parkinson’s disease

Steidel

Ruppert

Greuel

et al. 2022

npj Parkinsons Dis.

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“…WM areas with improved connectivity include the corpus callosum, fornix, and uncinate fasciculus. One explanation of these findings might be that increasing connectivity is indicative of compensatory changes, which have already been reported as compensation in later stages of the disease and the whole-brain/network scale that are probably due to the heterogeneous nature of PD ( 55 , 56 ). However, on the other hand, we also found other 5 paths where PD patients at 36 months of follow-up had lower connectivity than at baseline.…”

Section: Discussionmentioning

confidence: 81%

Structural connectivity and brain network analyses in Parkinson's disease: A cross-sectional and longitudinal study

et al. 2023

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IntroductionParkinson's disease (PD) is an idiopathic disease of the central nervous system characterized by both motor and non-motor symptoms. It is the second most common neurodegenerative disease. Magnetic resonance imaging (MRI) can reveal underlying brain changes associated with PD.ObjectiveIn this study, structural connectivity and white matter networks were analyzed by diffusion MRI and graph theory in a cohort of patients with PD and a cohort of healthy controls (HC) obtained from the Parkinson's Progression Markers Initiative (PPMI) database in a cross-sectional analysis. Furthermore, we investigated longitudinal changes in the PD cohort over 36 months.ResultCompared with the control group, participants with PD showed lower structural connectivity in several brain areas, including the corpus callosum, fornix, and uncinate fasciculus, which were also confirmed by a large effect-size. Additionally, altered connectivity between baseline and after 36 months was found in different network paths inside the white matter with a medium effect-size. Network analysis showed trends toward lower network density in PD compared with HC at baseline and after 36 months, though not significant after correction. Significant differences were observed in nodal degree and strength in several nodes.ConclusionIn conclusion, altered structural and network metrics in several brain regions, such as corpus callosum, fornix, and cingulum were found in PD, compared to HC. We also report altered connectivity in the PD group after 36 months, reflecting the impact of both PD pathology and aging processes. These results indicate that structural and network metrics might yield insight into network reorganization that occurs in PD.

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“…Both DC and BC will be computed at a regional level. Recently, we demonstrated that DC of the left dlPFC correlates with inhibition control performance in normal healthy individuals (unpublished pilot data) while the BC level of the caudate correlates with cognitive performance in non-demented PD patients (Wright et al, 2020).…”

Section: Rs-fmri Analysesmentioning

confidence: 89%

Changes in Metabolic Activity and Gait Function by Dual-Task Cognitive Game-Based Treadmill System in Parkinson’s Disease: Protocol of a Randomized Controlled Trial

Szturm

Kolesar

Mahana

et al. 2021

Front. Aging Neurosci.

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Balance and gait impairments, and consequently, mobility restrictions and falls are common in Parkinson’s disease (PD). Various cognitive deficits are also common in PD and are associated with increased fall risk. These mobility and cognitive deficits are limiting factors in a person’s health, ability to perform activities of daily living, and overall quality of life. Community ambulation involves many dual-task (DT) conditions that require processing of several cognitive tasks while managing or reacting to sudden or unexpected balance challenges. DT training programs that can simultaneously target balance, gait, visuomotor, and cognitive functions are important to consider in rehabilitation and promotion of healthy active lives. In the proposed multi-center, randomized controlled trial (RCT), novel behavioral positron emission tomography (PET) brain imaging methods are used to evaluate the molecular basis and neural underpinnings of: (a) the decline of mobility function in PD, specifically, balance, gait, visuomotor, and cognitive function, and (b) the effects of an engaging, game-based DT treadmill walking program on mobility and cognitive functions. Both the interactive cognitive game tasks and treadmill walking require continuous visual attention, and share spatial processing functions, notably to minimize any balance disturbance or gait deviation/stumble. The ability to “walk and talk” normally includes activation of specific regions of the prefrontal cortex (PFC) and the basal ganglia (site of degeneration in PD). The PET imaging analysis and comparison with healthy age-matched controls will allow us to identify areas of abnormal, reduced activity levels, as well as areas of excessive activity (increased attentional resources) during DT-walking. We will then be able to identify areas of brain plasticity associated with improvements in mobility functions (balance, gait, and cognition) after intervention. We expect the gait-cognitive training effect to involve re-organization of PFC activity among other, yet to be identified brain regions. The DT mobility-training platform and behavioral PET brain imaging methods are directly applicable to other diseases that affect gait and cognition, e.g., cognitive vascular impairment, Alzheimer’s disease, as well as in aging.

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Elevated caudate connectivity in cognitively normal Parkinson’s disease patients

Cited by 17 publications

References 63 publications

Longitudinal trimodal imaging of midbrain-associated network degeneration in Parkinson’s disease

Longitudinal trimodal imaging of midbrain-associated network degeneration in Parkinson’s disease

Structural connectivity and brain network analyses in Parkinson's disease: A cross-sectional and longitudinal study

Changes in Metabolic Activity and Gait Function by Dual-Task Cognitive Game-Based Treadmill System in Parkinson’s Disease: Protocol of a Randomized Controlled Trial

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