Large-scale resting state network correlates of cognitive impairment in Parkinson's disease and related dopaminergic deficits

ABSTRACTDopamine agonist (DA) medications commonly used to treat, or ‘normalise’, motor symptoms of Parkinson’s disease (PD) may lead to cognitive-neuropsychiatric side effects, such as increased impulsivity in decision-making. Subject-dependent variation in the neural response to dopamine modulation within cortico-basal ganglia circuitry is thought to play a key role in these latter, non-motor DA effects. This neuroimaging study combined resting-state functional magnetic resonance imaging (fMRI) with DA modification in patients with idiopathic PD, investigating whether brain ‘resting-state network’ (RSN) functional connectivity metrics identify disease-relevant effects of dopamine on systems-level neural processing. By comparing patients both ‘On’ and ‘Off’ their DA medications with age-matched, un-medicated healthy control subjects (HCs), we identified multiple non-normalising DA effects on frontal and basal ganglia RSN cortico-subcortical connectivity patterns in PD. Only a single isolated, potentially ‘normalising’, DA effect on RSN connectivity in sensori-motor systems was observed, within cerebro-cerebellar neurocircuitry. Impulsivity in reward-based decision-making was positively correlated with ventral striatal connectivity within basal ganglia circuitry in HCs, but not in PD patients. Overall, we provide brain systems-level evidence for anomalous DA effects in PD on large-scale networks supporting cognition and motivated behaviour. Moreover, findings suggest that dysfunctional striatal and basal ganglia signalling patterns in PD are compensated for by increased recruitment of other cortico-subcortical and cerebro-cerebellar systems.

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Resting-State Network Connectivity in Newly Diagnosed Drug-Naïve Parkinson’s Disease Patients With Mild Cognitive Impairment

10.21203/rs.3.rs-428251/v1 ◽

2021 ◽

Author(s):

Yanbing Hou ◽

Qianqian Wei ◽

Ruwei Ou ◽

Lingyu Zhang ◽

Xiaoqin Yuan ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Resting State ◽

Large Scale ◽

Rating Scale ◽

Fmri Data ◽

Newly Diagnosed ◽

Drug Naïve

Abstract Background: Cognitive impairment (CI) is one of the most frequent non-motor features in Parkinson's disease (PD). The frequency of mild cognitive impairment (MCI) was reported to exceed 40% in a large cohort of newly diagnosed PD patients.Method: Resting-state functional MRI (rs-fMRI) data was collected in 47 newly diagnosed drug-naïve PD patients (including 28 PD patients with MCI (PD-MCI subgroup) and 19 PD patients with cognitively unimpaired (PD-CU subgroup)) and 28 age- and sex-matched healthy controls (HCs). Independent component analysis (ICA) can decompose rs-fMRI data into resting state networks (RSNs). Brain intra- and inter-network alterations were investigated in RSNs among PD-MCI, PD-CU, and HCs groups.Results: Seven large-scale brain networks were extracted. The default mode network (DMN), visual network (VN) and sensorimotor network (SMN) were selectively vulnerable in the PD-MCI subgroup relative to the HC group. In PD-MCI patients, the reduced functional connectivity (FC) within the DMN was positively correlated with brief visuospatial memory test-revised (BVMT-R) scores (memory function); the reduced FC within the VN was positively correlated with clock copying test (CCT) scores (visuospatial function). In whole PD patients, the reduced FC within the SMN was negatively correlated with the Unified PD Rating Scale (UPDRS) part III scores. Moreover, FC between the SMN and limbic network, and between the ventral attention network (VAN) and VN were more prone to be damaged in PD patients.Conclusions: The DMN, VN and SMN were disrupted in PD-MCI patients. FC between the SMN and limbic network, and between the VAN and VN were also impaired in PD patients. The impaired intra- and inter-connectivity could provide further insights into the pathophysiological alterations of brain connectivity in newly diagnosed drug-naïve PD.

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Resting-state network connectivity in newly diagnosed drug-naïve Parkinson's disease patients with mild cognitive impairment

Parkinsonism & Related Disorders ◽

10.1016/j.parkreldis.2020.06.066 ◽

2020 ◽

Vol 79 ◽

pp. e11

Author(s):

Y. Hou ◽

Q. Wei ◽

R. Ou ◽

J. Yang ◽

H. Shang

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Resting State ◽

Network Connectivity ◽

Newly Diagnosed ◽

Resting State Network ◽

Drug Naïve

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“Resting-state fMRI in Parkinson's disease patients with cognitive impairment: A meta-analysis”: Answer to Wang and colleagues

Parkinsonism & Related Disorders ◽

10.1016/j.parkreldis.2019.07.014 ◽

2019 ◽

Vol 66 ◽

pp. 253-254

Author(s):

Amée F. Wolters ◽

Sjors C.F. van de Weijer ◽

Albert F.G. Leentjens ◽

Annelien A. Duits ◽

Heidi I.L. Jacobs ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Resting State ◽

Meta Analysis ◽

Resting State Fmri

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Large-scale exploratory genetic analysis of cognitive impairment in Parkinson's disease

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2017.04.009 ◽

2017 ◽

Vol 56 ◽

pp. 211.e1-211.e7 ◽

Cited By ~ 13

Author(s):

Ignacio F. Mata ◽

Catherine O. Johnson ◽

James B. Leverenz ◽

Daniel Weintraub ◽

John Q. Trojanowski ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Genetic Analysis ◽

Large Scale

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Alterations of regional homogeneity in Parkinson’s disease with mild cognitive impairment: a preliminary resting-state fMRI study

Neuroradiology ◽

10.1007/s00234-019-02333-7 ◽

2019 ◽

Vol 62 (3) ◽

pp. 327-334 ◽

Cited By ~ 1

Author(s):

Ming-ge Li ◽

Tie-fang Liu ◽

Tian-hao Zhang ◽

Zhi-ye Chen ◽

Bin-bin Nie ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Resting State ◽

Resting State Fmri ◽

Regional Homogeneity ◽

Fmri Study

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Distinct manifestation of cognitive deficits associate with different resting-state network disruptions in non-demented patients with Parkinson’s disease

Journal of Neurology ◽

10.1007/s00415-018-8755-5 ◽

2018 ◽

Vol 265 (3) ◽

pp. 688-700 ◽

Cited By ~ 12

Author(s):

Kazuya Kawabata ◽

Hirohisa Watanabe ◽

Kazuhiro Hara ◽

Epifanio Bagarinao ◽

Noritaka Yoneyama ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Deficits ◽

Resting State ◽

Resting State Network ◽

Network Disruptions

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Resting-state fMRI in Parkinson's disease patients with cognitive impairment: A meta-analysis

Parkinsonism & Related Disorders ◽

10.1016/j.parkreldis.2018.12.016 ◽

2019 ◽

Vol 62 ◽

pp. 16-27 ◽

Cited By ~ 16

Author(s):

Amée F. Wolters ◽

Sjors C.F. van de Weijer ◽

Albert F.G. Leentjens ◽

Annelien A. Duits ◽

Heidi I.L. Jacobs ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Resting State ◽

Meta Analysis ◽

Resting State Fmri

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The Cerebellum Is a Common Key for Visuospatial Execution and Attention in Parkinson’s Disease

Diagnostics ◽

10.3390/diagnostics11061042 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1042

Author(s):

Wataru Sako ◽

Takashi Abe ◽

Yuki Matsumoto ◽

Kazumi Nakamura ◽

Shotaro Haji ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Resting State ◽

Cognitive Domain ◽

Underlying Network ◽

Magnetic Resonance Imaging Mri ◽

State Examination ◽

Orientation Domain ◽

Normal Controls

Cognitive decline affects the clinical course in patients with Parkinson’s disease (PD) and contributes to a poor prognosis. However, little is known about the underlying network-level abnormalities associated with each cognitive domain. We aimed to identify the networks related to each cognitive domain in PD using resting-state functional magnetic resonance imaging (MRI). Forty patients with PD and 15 normal controls were enrolled. All subjects underwent MRI and the Mini-Mental State Examination. Furthermore, the cognitive function of patients with PD was assessed using the Montreal Cognitive Assessment (MoCA). We used independent component analysis of the resting-state functional MRI for functional segmentation, followed by reconstruction to identify each domain-related network, to predict scores in PD using multiple regression models. Six networks were identified, as follows: the visuospatial-executive-domain-related network (R2 = 0.54, p < 0.001), naming-domain-related network (R2 = 0.39, p < 0.001), attention-domain-related network (R2 = 0.86, p < 0.001), language-domain-related network (R2 = 0.64, p < 0.001), abstraction-related network (R2 = 0.10, p < 0.05), and orientation-domain-related network (R2 = 0.64, p < 0.001). Cerebellar lobule VII was involved in the visuospatial-executive-domain-related and attention-domain-related networks. These two domains are involved in the first three listed nonamnestic cognitive impairment in the diagnostic criteria for PD with dementia (PDD). Furthermore, Brodmann area 10 contributed most frequently to each domain-related network. Collectively, these findings suggest that cerebellar lobule VII may play a key role in cognitive impairment in nonamnestic types of PDD.

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