Effects of dopamine agonist treatment on resting-state network connectivity in Parkinson’s disease

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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Cognitive impairment and resting-state network connectivity in Parkinson's disease

Human Brain Mapping ◽

10.1002/hbm.22622 ◽

2014 ◽

Vol 36 (1) ◽

pp. 199-212 ◽

Cited By ~ 150

Author(s):

Hugo-Cesar Baggio ◽

Bàrbara Segura ◽

Roser Sala-Llonch ◽

Maria-José Marti ◽

Francesc Valldeoriola ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Resting State ◽

Network Connectivity ◽

Resting State Network

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Resting-state network connectivity in cognitively unimpaired drug-naïve patients with rigidity-dominant Parkinson’s disease

Parkinsonism & Related Disorders ◽

10.1016/j.parkreldis.2017.11.260 ◽

2018 ◽

Vol 46 ◽

pp. e75-e76

Author(s):

Y. Hou ◽

J. Yang ◽

C. Luo ◽

R. Ou ◽

W. Song ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Resting State ◽

Network Connectivity ◽

Resting State Network ◽

Drug Naïve

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Distinct large-scale networks are associated with motor and nonmotor symptoms in Parkinson’s disease

10.1101/2020.05.13.093724 ◽

2020 ◽

Author(s):

Sule Tinaz ◽

Serageldin Kamel ◽

Sai S. Aravala ◽

Mine Sezgin ◽

Mohamed Elfil ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Functional Connectivity ◽

Large Scale ◽

Emotional Dysregulation ◽

Disease Stage ◽

Nonmotor Symptoms ◽

Large Scale Networks ◽

Brain Data

ABSTRACTParkinson’s disease (PD) is characterized clinically by various motor and nonmotor symptoms. The underlying neuroanatomical correlates of nonmotor symptoms in PD remain poorly understood. We investigated the differences and commonalities in the neuroanatomical correlates 1) between highly prevalent nonmotor features including fatigue, anxiety, depression, and apathy, and 2) between these nonmotor features and motor severity in nondemented subjects with mild PD (Hoehn & Yahr disease stage 2) using structural and functional magnetic resonance imaging. Compared to matched controls, the PD group showed atrophy in the basal ganglia and superior frontal cortex. Motor severity correlated with cortical thinning in frontotemporal regions, as well as with reduced functional connectivity between the frontostriatal and cerebellar networks. The composite nonmotor symptom severity did not show any correlation with the structural brain data, but correlated with reduced functional connectivity in a large-scale network consisting of frontostriatal, parietotemporal, and cerebellar nodes. The individual components of the nonmotor symptoms also mapped onto specific neural networks. Our study shows that motor and nonmotor features in PD are associated with distinct large-scale networks. The basal ganglia and cerebellum are core regions in all of these networks. The abnormal functional connectivity in the nonmotor network seems to be related to cognitive and emotional dysregulation and may have implications for future cognitive decline in PD.

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Networks Are Associated With Depression in Patients With Parkinson’s Disease: A Resting-State Imaging Study

Frontiers in Neuroscience ◽

10.3389/fnins.2020.573538 ◽

2021 ◽

Vol 14 ◽

Author(s):

Haiyan Liao ◽

Sainan Cai ◽

Qin Shen ◽

Jie Fan ◽

Tianyu Wang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Resting State ◽

Large Scale ◽

Brain Connectivity ◽

Imaging Study ◽

Sensorimotor Network ◽

Depression Level ◽

Large Scale Networks ◽

The Right

BackgroundDisturbance of networks was recently proposed to be associated with the occurrence of depression in Parkinson’s disease (PD). However, the neurobiological mechanism of depression underlying PD remains unclear.ObjectiveThis study was conducted to investigate whether intra-network and inter-network brain connectivity is differently changed in PD patients with and without depression (PDD and PDND patients, respectively).MethodsForty-one PDD patients, 64 PDND patients, and 55 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (fMRI). The default mode network (DMN), executive control network (ECN), salience network (SN), precuneus network (PCUN), and sensorimotor network (SMN) were extracted using independent component analysis (ICA), and then the functional connectivity (FC) values within and between these networks were measured.ResultsPDD patients exhibited abnormal FC values within the DMN, ECN, SN, PCUN, and SMN. In addition, PDD patients demonstrated decreased connectivity between anterior SN (aSN) and bilateral ECN, between posterior SN (pSN) and dorsal DMN (dDMN), and between PCUN and dDMN/SMN/bilateral ECN. Connectivity within the left hippocampus of dDMN and the right medial superior frontal gyrus of aSN was a significant predictor of depression level in PD patients.ConclusionsAberrant intra- and inter-network FC is involved in several important hubs in the large-scale networks, which can be a biomarker for distinguishing PDD from PDND.

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