Functional connectivity of spoken language processing in early-stage Parkinson’s disease: an MEG study

Background: Cognitive impairment is one of the most prominent non-motor symptoms in Parkinson's disease (PD), due in part to known cerebellar dysfunctions. Furthermore, previous studies have reported altered cerebellar functional connectivity (FC) in PD patients. Yet whether these changes are also due to the cognitive deficits in PD remain unclear.Methods: A total of 122 non-dementia participants, including 64 patients with early PD and 58 age- and gender-matched elderly controls were stratified into four groups based on their cognitive status (normal cognition vs. cognitive impairment). Cerebellar volumetry and FC were investigated by analyzing, respectively, structural and resting-state functional MRI data among groups using quality control and quantitative measures. Correlation analysis between MRI metrics and clinical features (motor and cognitive scores) were performed.Results: Compared to healthy control subjects with no cognitive deficits, altered cerebellar FC were observed in early PD participants with both motor and cognitive deficits, but not in PD patients with normal cognition, nor elderly subjects showing signs of a cognitive impairment. Moreover, connectivity between the “motor” cerebellum and SMA was positively correlated with motor scores, while intracerebellar connectivity was positively correlated with cognitive scores in PD patients with cognitive impairment. No cerebellar volumetric difference was observed between groups.Conclusions: These findings show that altered cerebellar FC during resting state in early PD patients may be driven not solely by the motor deficits, but by cognitive deficits as well, hence highlighting the interplay between motor and cognitive functioning, and possibly reflecting compensatory mechanisms, in the early PD.

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Altered Cortical Cholinergic Network in Parkinson’s Disease at Different Stage: A Resting-State fMRI Study

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.723948 ◽

2021 ◽

Vol 13 ◽

Author(s):

Wenshuang Sheng ◽

Tao Guo ◽

Cheng Zhou ◽

Jingjing Wu ◽

Ting Gao ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Functional Connectivity ◽

Resting State ◽

Cholinergic System ◽

Rating Scale ◽

Clinical Symptoms ◽

Early Stage ◽

Brain Magnetic Resonance Imaging ◽

Cholinergic Innervation

The cholinergic system is critical in Parkinson’s disease (PD) pathology, which accounts for various clinical symptoms in PD patients. The substantia innominata (SI) provides the main source of cortical cholinergic innervation. Previous studies revealed cholinergic-related dysfunction in PD pathology at early stage. Since PD is a progressive disorder, alterations of cholinergic system function along with the PD progression have yet to be elucidated. Seventy-nine PD patients, including thirty-five early-stage PD patients (PD-E) and forty-four middle-to-late stage PD patients (PD-M), and sixty-four healthy controls (HC) underwent brain magnetic resonance imaging and clinical assessments. We employed seed-based resting-state functional connectivity analysis to explore the cholinergic-related functional alterations. Correlation analysis was used to investigate the relationship between altered functional connectivity and the severity of motor symptoms in PD patients. Results showed that both PD-E and PD-M groups exhibited decreased functional connectivity between left SI and left frontal inferior opercularis areas and increased functional connectivity between left SI and left cingulum middle area as well as right primary motor and sensory areas when comparing with HC. At advanced stages of PD, functional connectivity in the right primary motor and sensory areas was further increased. These altered functional connectivity were also significantly correlated with the Unified Parkinson’s Disease Rating Scale motor scores. In conclusion, this study illustrated that altered cholinergic function plays an important role in the motor disruptions in PD patients both in early stage as well as during the progression of the disease.

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Sleep-State Dependent Alterations in Brain Functional Connectivity under Urethane Anesthesia in a Rat Model of Early-Stage Parkinson’s Disease

eNeuro ◽

10.1523/eneuro.0456-18.2019 ◽

2019 ◽

Vol 6 (1) ◽

pp. ENEURO.0456-18.2019 ◽

Cited By ~ 3

Author(s):

Ekaterina Zhurakovskaya ◽

Juuso Leikas ◽

Tiina Pirttimäki ◽

Francesc Casas Mon ◽

Mikko Gynther ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Functional Connectivity ◽

Rat Model ◽

Early Stage ◽

Sleep State ◽

Urethane Anesthesia ◽

State Dependent ◽

Brain Functional Connectivity

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Increased cortico-cortical functional connectivity in early-stage Parkinson's disease: An MEG study

NeuroImage ◽

10.1016/j.neuroimage.2008.02.027 ◽

2008 ◽

Vol 41 (2) ◽

pp. 212-222 ◽

Cited By ~ 98

Author(s):

D. Stoffers ◽

J.L.W. Bosboom ◽

J.B. Deijen ◽

E.Ch. Wolters ◽

C.J. Stam ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Functional Connectivity ◽

Early Stage

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Reduced functional connectivity in early-stage drug-naive Parkinson's disease: a resting-state fMRI study

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2013.08.018 ◽

2014 ◽

Vol 35 (2) ◽

pp. 431-441 ◽

Cited By ~ 98

Author(s):

ChunYan Luo ◽

Wei Song ◽

Qin Chen ◽

ZhenZhen Zheng ◽

Ke Chen ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Functional Connectivity ◽

Resting State ◽

Early Stage ◽

Resting State Fmri ◽

Fmri Study ◽

Drug Naïve

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Spoken Language Processing: A Convergent Approach to Conceptualizing (Central) Auditory Processing

ASHA Leader ◽

10.1044/leader.ftr2.11082006.6 ◽

2006 ◽

Vol 11 (8) ◽

pp. 6-33 ◽

Cited By ~ 1

Author(s):

Larry Medwetsky

Keyword(s):

Language Processing ◽

Auditory Processing ◽

Spoken Language ◽

Central Auditory Processing ◽

Spoken Language Processing ◽

Convergent Approach

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Association of the Non-Motor Burden with Patterns of Striatal Dopamine Loss in de novo Parkinson’s Disease

Journal of Parkinson s Disease ◽

10.3233/jpd-202127 ◽

2020 ◽

Vol 10 (4) ◽

pp. 1541-1549

Author(s):

Seok Jong Chung ◽

Sangwon Lee ◽

Han Soo Yoo ◽

Yang Hyun Lee ◽

Hye Sun Lee ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

De Novo ◽

Early Stage ◽

Striatal Dopamine ◽

Motor Deficits ◽

Dopamine Depletion ◽

Severe Motor ◽

Severe Group ◽

Striatal Dopamine Depletion

Background: Striatal dopamine deficits play a key role in the pathogenesis of Parkinson’s disease (PD), and several non-motor symptoms (NMSs) have a dopaminergic component. Objective: To investigate the association between early NMS burden and the patterns of striatal dopamine depletion in patients with de novo PD. Methods: We consecutively recruited 255 patients with drug-naïve early-stage PD who underwent 18F-FP-CIT PET scans. The NMS burden of each patient was assessed using the NMS Questionnaire (NMSQuest), and patients were divided into the mild NMS burden (PDNMS-mild) (NMSQuest score <6; n = 91) and severe NMS burden groups (PDNMS-severe) (NMSQuest score >9; n = 90). We compared the striatal dopamine transporter (DAT) activity between the groups. Results: Patients in the PDNMS-severe group had more severe parkinsonian motor signs than those in the PDNMS-mild group, despite comparable DAT activity in the posterior putamen. DAT activity was more severely depleted in the PDNMS-severe group in the caudate and anterior putamen compared to that in the PDMNS-mild group. The inter-sub-regional ratio of the associative/limbic striatum to the sensorimotor striatum was lower in the PDNMS-severe group, although this value itself lacked fair accuracy for distinguishing between the patients with different NMS burdens. Conclusion: This study demonstrated that PD patients with severe NMS burden exhibited severe motor deficits and relatively diffuse dopamine depletion throughout the striatum. These findings suggest that the level of NMS burden could be associated with distinct patterns of striatal dopamine depletion, which could possibly indicate the overall pathological burden in PD.

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