Neural substrates of excessive daytime sleepiness in early drug naïve Parkinson's disease: A resting state functional MRI study

Wen, Ming‐Ching; Ng, Samuel Yong‐Ern; Heng, Hannah S. E.; Chao, Yin Xia; Chan, Ling‐Ling; Tan, Eng King; Tan, Louis C.S.

doi:10.1016/j.parkreldis.2016.01.012

Cited by 38 publications

(29 citation statements)

References 26 publications

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“…Our results suggest that mildly to moderately affected PD patients have reduced connectivity affecting all brain subnetworks in the off ‐medication state and that levodopa imparts a restoring effect across these networks. This is consistent with known degeneration of dopaminergic neurons in PD that disrupt more widespread cognitive and limbic circuits in addition to motor circuits; however, nondopaminergic systems are also affected in PD and could contribute to our finding widespread disturbances in functional connectivity …”

Section: Discussionsupporting

confidence: 90%

Levodopa modulates small‐world architecture of functional brain networks in Parkinson's disease

et al. 2016

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Background PD is associated with disrupted connectivity to a large number of distributed brain regions. How the disease alters the functional topological organization of the brain, however, remains poorly understood. Furthermore, how levodopa modulates network topology in PD is largely unknown. Objectives We used resting state functional MRI (rsfMRI) and graph theory to determine how small-world architecture is altered in PD and affected by levodopa administration. Methods Twenty-one PD patients and 20 controls underwent functional MRI scanning. PD patients were scanned off medication and one hour after 200mg levodopa. Imaging data were analyzed using 226 nodes comprising 10 intrinsic brain networks. Correlation matrices were generated for each subject and converted into cost thresholded, binarized adjacency matrices. Cost-integrated whole brain global and local efficiencies were compared across groups and tested for relationships with disease duration and severity. Results Data from two patients and four controls were excluded due to excess motion. Patients off medication showed no significant changes in global efficiency and overall local efficiency, but in a subnetwork analysis did show increased local efficiency in Executive (p=0.006), and Salience (p=0.018) networks. Levodopa significantly decreased local (p=0.039) efficiency in patients except within the Subcortical network where it significantly increased local efficiency (p=0.007). Conclusions Levodopa modulates global and local efficiency measures of small-world topology in PD suggesting that degeneration of nigrostriatal neurons in PD may be associated with a large-scale network reorganization, and that levodopa tends to normalize the disrupted network topology in PD.

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Section: Discussionsupporting

confidence: 90%

Levodopa modulates small‐world architecture of functional brain networks in Parkinson's disease

et al. 2016

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“…Study aims, methodology, and details of study assessments are available on the PPMI website 1 . The inclusion and exclusion criteria were described previously in detail (Wen et al, 2016;Chahine et al, 2019). Institutional review boards approved the study at PPMI sites, and written informed consent was obtained.…”

Section: Participantsmentioning

confidence: 99%

Striatum Shape Hypertrophy in Early Stage Parkinson’s Disease With Excessive Daytime Sleepiness

Gong

Yang

et al. 2020

Front. Neurosci.

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Introduction: Excessive daytime sleepiness (EDS) is one of the common and burdensome non-motor symptoms of Parkinson's disease (PD). However, the underlying neuropathology mechanism in PD patients with EDS (PD-EDS) remains unclear. The present study aims to delineate potential locations of structural alteration of subcortical regions in early stage and drug-naïve PD-EDS. Methods: The study had 252 patients with PD and 92 matched healthy controls (HC). EDS was estimated with the Epworth Sleepiness Scale, with a cutoff of 10. Ultimately, 59 patients were considered as PD-EDS. The remaining 193 were PD patients without EDS (PD-nEDS). FMRIB's Integrated Registration and Segmentation Tool (FIRST) was employed to assess the volumetric and surface alterations of subcortical nuclei in PD and PD-EDS. Results: Volumetric analyses found no difference in the subcortical nucleus volume between PD and HC, or PD-EDS and PD-nEDS groups. The shape analyses revealed the local atrophic changes in bilateral caudate and right putamen in patients with PD. In addition, the hypertrophic changes were located in the right putamen and left pallidum in PD-EDS than in PD-nEDS. Conclusion: Our findings revealed the regional hypertrophy of the striatum in PD-EDS. Our results indicate that local hypertrophic striatum would be a valuable early biomarker for detecting the alteration in PD-EDS. The shape analysis contributes valuable information when investigating PD-EDS.

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“…On the other hand, very recently, microstructural abnormalities in drug‐naive PD patients with EDS involving the fornix, inferior longitudinal fasciculus, and inferior and middle cerebellar peduncles have been found, suggesting that EDS also could occur in the early stage of PD and without the influence of dopaminergic therapy . Accordingly, using resting‐state fMRI, Wen and colleagues showed widespread abnormalities in functional connectivity in drug‐naive PD patients with EDS compared with patients without, suggesting the presence of neural downregulation and compensatory mechanisms even at an early stage of disease.…”

Section: Resultsmentioning

confidence: 99%

MRI of Motor and Nonmotor Therapy‐Induced Complications in Parkinson's Disease

2020

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Levodopa therapy remains the most effective drug for the treatment of Parkinson's disease, and it is associated with the greatest improvement in motor function as assessed by the Unified Parkinson's Disease Rating Scale. Dopamine agonists have also proven their efficacy as monotherapy in early Parkinson's disease but also as adjunct therapy. However, the chronic use of dopaminergic therapy is associated with disabling motor and nonmotor side effects and complications, among which levodopa‐induced dyskinesias and impulse control behaviors are the most common. The underlying mechanisms of these disorders are not fully understood. In the last decade, classic neuroimaging methods and more sophisticated techniques, such as analysis of gray‐matter structural imaging and functional magnetic resonance imaging, have given access to anatomical and functional abnormalities, respectively, in the brain. This review presents an overview of structural and functional brain changes associated with motor and nonmotor therapy‐induced complications in Parkinson's disease. Magnetic resonance imaging may offer structural and/or functional neuroimaging biomarkers that could be used as predictive signs of development, maintenance, and progression of these complications. Neurophysiological tools, such as theta burst stimulation and transcranial magnetic stimulation, might help us to integrate neuroimaging findings and clinical features and could be used as therapeutic options, translating neuroimaging data into clinical practice. © 2020 International Parkinson and Movement Disorder Society

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Neural substrates of excessive daytime sleepiness in early drug naïve Parkinson's disease: A resting state functional MRI study

Cited by 38 publications

References 26 publications

Levodopa modulates small‐world architecture of functional brain networks in Parkinson's disease

Levodopa modulates small‐world architecture of functional brain networks in Parkinson's disease

Striatum Shape Hypertrophy in Early Stage Parkinson’s Disease With Excessive Daytime Sleepiness

MRI of Motor and Nonmotor Therapy‐Induced Complications in Parkinson's Disease

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