Increased functional connectivity of thalamic subdivisions in patients with Parkinson’s disease

AbstractParkinson’s disease (PD) affects 2-3% of the population over the age of 65 with loss of dopaminergic neurons in the substantia nigra impacting the functioning of basal ganglia-thalamocortical circuits. The precise role played by the thalamus is unknown, despite its critical role in the functioning of the cerebral cortex, and the abnormal neuronal activity of the structure in PD. Our objective was to more clearly elucidate how functional connectivity and morphology of the thalamus are impacted in PD (n = 32) compared to Controls (n = 20). To investigate functional connectivity of the thalamus we subdivided the structure into two important regions-of-interest, the first with putative connections to the motor cortices and the second with putative connections to prefrontal cortices. We then investigated potential differences in the size and shape of the thalamus in PD, and how morphology and functional connectivity relate to clinical variables. Our data demonstrate that PD is associated with increases in functional connectivity between motor subdivisions of the thalamus and the supplementary motor area, and between prefrontal thalamic subdivisions and nuclei of the basal ganglia, anterior and dorsolateral prefrontal cortices, as well as the anterior and paracingulate gyri. These results suggest that PD is associated with increased functional connectivity of subdivisions of the thalamus which may be indicative alterations to basal ganglia-thalamocortical circuitry.

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Impaired Temporal Discrimination in Parkinson's Disease: Temporal Processing of Brief Durations as an Indicator of Degeneration of Dopaminergic Neurons in the Basal Ganglia

International Journal of Neuroscience ◽

10.3109/00207459708986364 ◽

1997 ◽

Vol 91 (1-2) ◽

pp. 45-55 ◽

Cited By ~ 66

Author(s):

Thomas Rammsayer ◽

Wilhelm Classen

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Temporal Processing ◽

Dopaminergic Neurons ◽

Temporal Discrimination

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Similar Circuits but Different Connectivity Patterns Between The Cerebellum, Basal Ganglia, and Supplementary Motor Area In Early Parkinson's Disease Patients and Controls During Predictive Motor Timing

Journal of Neuroimaging ◽

10.1111/jon.12030 ◽

2013 ◽

Vol 23 (4) ◽

pp. 452-462 ◽

Cited By ~ 19

Author(s):

Ivica Husárová ◽

Michal Mikl ◽

Ovidiu V. Lungu ◽

Radek Mareček ◽

Jiří Vaníček ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Supplementary Motor Area ◽

Motor Area ◽

Motor Timing ◽

Connectivity Patterns ◽

Early Parkinson’S Disease

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Autophagin-3 (ATG4C) is differentially expressed in the brains of patients with Parkinson’s Disease.

10.31219/osf.io/6p529 ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Substantia Nigra ◽

Dopaminergic Neurons ◽

Differentially Expressed ◽

Gene Encoding ◽

Microarray Datasets

Parkinson’s Disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra of the basal ganglia (1). We mined published microarray datasets (2, 3) to identify genes whose expression was most different in the substantial nigra of patients with PD as compared to that of non-affected patients. We identified significant changes in expression of the gene encoding autophagin-3 (ATG4C) in the substantia nigra of patients with PD.

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Artemisinin Attenuated Oxidative Stress and Apoptosis by Inhibiting Autophagy in MPP+-treated SH-SY5Y Cell

10.21203/rs.3.rs-90741/v1 ◽

2020 ◽

Author(s):

Junqiang Yan ◽

Hongxia Ma ◽

Xiaoyi Lai ◽

Jiannan Wu ◽

Anran Liu ◽

...

Keyword(s):

Oxidative Stress ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Dopaminergic Neurons ◽

Artemisia Annua ◽

Cell Model ◽

Neuroprotective Effect ◽

Critical Role ◽

Neuroprotective Effects ◽

Pre Treatment

Abstract Background Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's. The drugs currently used to treat PD cannot inhibit the development of PD, and long-term use produces severe drug resistance and adverse reaction. Artemisinin (ART) is an active ingredient of Artemisia annua and has a neuroprotective effect, but the mechanism is still unclear. This study was designed to investigate the neuroprotective effect of ART in MPP+-treated SH-SY5Y cells. Results There was no significant cytotoxicity when the ART concentration was under. 40μM. The 20μM ART for 24h could increase the cell viability by reducing oxidative stress and cell apoptosis in MPP+-treated SH-SY5Y cell. In addition, immunoblot and immunofluorescence results showed that MPP+ treatment increased the expression of Beclin1, LC3II/LC3I and decreased the expression of P62, while ART can reverse the changes caused by MPP+. Discussion More and more researches reported that ART and its derivates have neuroprotective effects through anti-oxidant and anti-apoptosis. we found that pre-treated cells with 20μM ART for 4h could significantly increase the viability in Parkinson's disease cell model. The oxidative stress and apoptosis were the main reason for the degeneration of dopaminergic neurons, while artemisinin can attenuate oxidative stress and apoptosis in MPP+-lesioned dopaminergic neurons. The levels of autophagy proteins LC3II/I, Beclin1 and P62 also showed that MPP+ increased the autophagy level, and pre-treatment with ART decreased the autophagy level, which may be the pathological mechanism for artemisinin to reduce oxidative stress damage and apoptosis. Conclusions These results indicate that ART exerts a positive effect on MPP+-treated SH-SY5Y cells in terms of anti-oxidative stress and anti-apoptosis. These effects may be related to autophagy. These findings contribute to a better understanding of the critical role of ART in PD treatment.

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Insight Into the Emerging Role of Striatal Neurotransmitters in the Pathophysiology of Parkinson’s Disease and Huntington’s Disease: A Review

Current Neuropharmacology ◽

10.2174/1570159x16666180302115032 ◽

2019 ◽

Vol 17 (2) ◽

pp. 165-175 ◽

Cited By ~ 14

Author(s):

Sumit Jamwal ◽

Puneet Kumar

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Neuronal Death ◽

Critical Role ◽

Altered Level ◽

Excitotoxic Neuronal Death

Alteration in neurotransmitters signaling in basal ganglia has been consistently shown to significantly contribute to the pathophysiological basis of Parkinson’s disease and Huntington’s disease. Dopamine is an important neurotransmitter which plays a critical role in coordinated body movements. Alteration in the level of brain dopamine and receptor radically contributes to irregular movements, glutamate mediated excitotoxic neuronal death and further leads to imbalance in the levels of other neurotransmitters viz. GABA, adenosine, acetylcholine and endocannabinoids. This review is based upon the data from clinical and preclinical studies to characterize the role of various striatal neurotransmitters in the pathogenesis of Parkinson’s disease and Huntington’s disease. Further, we have collected data of altered level of various neurotransmitters and their metabolites and receptor density in basal ganglia region. Although the exact mechanisms underlying neuropathology of movement disorders are not fully understood, but several mechanisms related to neurotransmitters alteration, excitotoxic neuronal death, oxidative stress, mitochondrial dysfunction, neuroinflammation are being put forward. Restoring neurotransmitters level and downstream signaling has been considered to be beneficial in the treatment of Parkinson’s disease and Huntington’s disease. Therefore, there is an urgent need to identify more specific drugs and drug targets that can restore the altered neurotransmitters level in brain and prevent/delay neurodegeneration.

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The organization of the basal ganglia functional connectivity network is non-linear in Parkinson's disease

NeuroImage Clinical ◽

10.1016/j.nicl.2019.101708 ◽

2019 ◽

Vol 22 ◽

pp. 101708 ◽

Cited By ~ 3

Author(s):

Clara Rodriguez-Sabate ◽

Ingrid Morales ◽

Jesus N. Lorenzo ◽

Manuel Rodriguez

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Functional Connectivity ◽

Non Linear

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Dissociation of Neural Mechanisms for Intersensory Timing Deficits in Parkinson’s Disease

Timing & Time Perception ◽

10.1163/22134468-00002025 ◽

2014 ◽

Vol 2 (2) ◽

pp. 145-168 ◽

Cited By ~ 14

Author(s):

Deborah L. Harrington ◽

Gabriel N. Castillo ◽

Jason D. Reed ◽

David D. Song ◽

Irene Litvan ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Functional Connectivity ◽

Visual Information ◽

Anterior Insula ◽

Visual Signals ◽

Controlled Attention ◽

Cortical Regions ◽

Attention Demands

This study investigated the ability of individuals with Parkinson’s disease (PD) to synthesize temporal information across the senses, namely audition and vision. Auditory signals (A) are perceived as lasting longer than visual signals (V) when they are compared together, since attention is captured and sustained more easily than for visual information. We used the audiovisual illusion to probe for disturbances in brain networks that govern the resolution of time in two intersensory conditions that putatively differ in their attention demands. PD patients and controls judged the relative duration of successively presented pairs of unimodal (AA, VV) and crossmodal (VA, AV) signals whilst undergoing fMRI. There were four main findings. First, underestimation of time was exaggerated in PD when timing depended on controlled attention (AV), whereas subtle deficits were found when audition dominated and attention was more easily sustained (VA). Second, group differences in regional activation were observed only for the AV-unimodal comparison, where the PD group failed to modulate basal ganglia, anterior insula, and inferior cerebellum activity in accord with the timing condition. Third, the intersensory timing conditions were dissociated by patterns of abnormal functional connectivity. When intersensory timing emphasized controlled attention, patients showed weakened connectivity of the cortico-thalamus-basal ganglia (CTBG) circuit and the anterior insula with widespread cortical regions, yet enhanced cerebellar connectivity. When audition dominated intersensory timing, patients showed enhanced connectivity of CTBG elements, the anterior insula, and the cerebellum with the caudate tail and frontal cortex. Fourth, abnormal connectivity measures showed excellent sensitivity and specificity in accurately classifying subjects. The results demonstrate that intersensory timing deficits in PD were well characterized by context-dependent patterns of functional connectivity within a presumed core timing system (CTBG) and a ventral attention hub (anterior insula), and enhanced cerebellar connectivity irrespective of the hypothesized attention demands of timing.

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Neural signatures of hyperdirect pathway activity in Parkinson’s disease

Nature Communications ◽

10.1038/s41467-021-25366-0 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Ashwini Oswal ◽

Chunyan Cao ◽

Chien-Hung Yeh ◽

Wolf-Julian Neumann ◽

James Gratwicke ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Supplementary Motor Area ◽

Computational Modelling ◽

Motor Area ◽

Internal Globus Pallidus ◽

Pathway Activity ◽

High Beta ◽

Beta Frequency

AbstractParkinson’s disease (PD) is characterised by the emergence of beta frequency oscillatory synchronisation across the cortico-basal-ganglia circuit. The relationship between the anatomy of this circuit and oscillatory synchronisation within it remains unclear. We address this by combining recordings from human subthalamic nucleus (STN) and internal globus pallidus (GPi) with magnetoencephalography, tractography and computational modelling. Coherence between supplementary motor area and STN within the high (21–30 Hz) but not low (13-21 Hz) beta frequency range correlated with ‘hyperdirect pathway’ fibre densities between these structures. Furthermore, supplementary motor area activity drove STN activity selectively at high beta frequencies suggesting that high beta frequencies propagate from the cortex to the basal ganglia via the hyperdirect pathway. Computational modelling revealed that exaggerated high beta hyperdirect pathway activity can provoke the generation of widespread pathological synchrony at lower beta frequencies. These findings suggest a spectral signature and a pathophysiological role for the hyperdirect pathway in PD.

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