Age-related changes in saccadic eye movements in healthy subjects and patients with Parkinson’s disease

Movement in Parkinson’s disease (PD) is fragmented, and the patients depend on visual information in their behavior. This suggests that the patients may have deficits in internally monitoring their own movements. Internal monitoring of movements is assumed to rely on corollary discharge signals that enable the brain to predict the sensory consequences of actions. We studied early-stage PD patients (N = 14), and age-matched healthy control participants (N = 14) to examine whether PD patients reveal deficits in updating their sensory representations after eye movements. The participants performed a double-saccade task where, in order to accurately fixate a second target, the participant must correct for the displacement caused by the first saccade. In line with previous reports, the patients had difficulties in fixating the second target when the eye movement was performed without visual guidance. Furthermore, the patients had difficulties in taking into account the error in the first saccade when making a saccade toward the second target, especially when eye movements were made toward the side with dominant motor symptoms. Across PD patients, the impairments in saccadic eye movements correlated with the integrity of the dopaminergic system as measured with [123I]FP-CIT SPECT: Patients with lower striatal (caudate, anterior putamen, and posterior putamen) dopamine transporter binding made larger errors in saccades. This effect was strongest when patients made memory-guided saccades toward the second target. Our results provide tentative evidence that the motor deficits in PD may be partly due to deficits in internal monitoring of movements.

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Pharmacologic MRI (phMRI) as a tool to differentiate Parkinson's disease–related from age-related changes in basal ganglia function

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2014.10.014 ◽

2015 ◽

Vol 36 (2) ◽

pp. 1174-1182 ◽

Cited By ~ 7

Author(s):

Anders H. Andersen ◽

Peter A. Hardy ◽

Eric Forman ◽

Greg A. Gerhardt ◽

Don M. Gash ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Age Related ◽

Age Related Changes

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Dopamine and eye movement control in Parkinson’s disease: deficits in corollary discharge signals?

10.1101/245381 ◽

2018 ◽

Author(s):

Henry Railo ◽

Henri Olkoniemi ◽

Enni Eeronheimo ◽

Oona Pääkkonen ◽

Juho Joutsa ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Eye Movements ◽

Eye Movement ◽

Visual Information ◽

Early Stage ◽

Movement Control ◽

Saccadic Eye Movements ◽

Corollary Discharge ◽

Motor Deficits

Movement in Parkinson’s disease (PD) is fragmented, and the patients depend on visual information in their behavior. This suggests that the patients may have deficits in internally monitoring their own movements. Internal monitoring of movements is assumed to rely on corollary discharge signals that enable the brain to predict the sensory consequences of actions. We studied early-stage PD patients (N=14), and age-matched healthy control participants (N=14) to examine whether PD patients reveal deficits in updating their sensory representations after eye movements. The participants performed a double-saccade task where, in order to accurately fixate a second target, the participant must correct for the displacement caused by the first saccade. In line with previous reports, the patients had difficulties in fixating the second target when the eye movement was performed without visual guidance. Furthermore, the patients had difficulties in taking into account the error in the first saccade when making a saccade towards the second target, especially when eye movements were made towards the side with dominant motor symptoms. Across PD patients, the impairments in saccadic eye movements correlated with the integrity of the dopaminergic system as measured with [123I]FP-CIT SPECT: Patients with lower striatal (caudate, anterior putamen and posterior putamen) dopamine transporter binding made larger errors in saccades. This effect was strongest when patients made memory-guided saccades towards the second target. Our results provide tentative evidence that the motor deficits in PD may be partly accounted by deficits in internal monitoring of movements.

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Expression Profiling of Blood microRNAs 885, 361, and 17 in the Patients with the Parkinson’s disease: Integrating Interaction Data to Uncover the Possible Triggering Age-Related Mechanisms

Scientific Reports ◽

10.1038/s41598-019-50256-3 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Molood Behbahanipour ◽

Maryam Peymani ◽

Mehri Salari ◽

Motahare-Sadat Hashemi ◽

Mohammad Hossein Nasr-Esfahani ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Disease Severity ◽

Cellular Senescence ◽

Healthy Subjects ◽

Target Genes ◽

Healthy Controls ◽

Early Stages ◽

Age Related ◽

Advanced Stages

Abstract MicroRNAs (miRNAs) have been reported to contribute to the pathophysiology of the Parkinson’s disease (PD), an age related-neurodegenerative disorder. The aim of present study was to compare the expression profiles of a new set of candidate miRNAs related to aging and cellular senescence in peripheral blood mononuclear cells (PBMCs) obtained from the PD patients with healthy controls and then in the early and advanced stages of the PD patients with their controls to clarify whether their expression was correlated with the disease severity. We have also proposed a consensus-based strategy to interpret the miRNAs expression data to gain a better insight into the molecular regulatory alterations during the incidence of PD. We evaluated the miRNA expression levels in the PBMCs obtained from 36 patients with PD and 16 healthy controls by the reverse transcription-quantitative real-time PCR and their performance to discriminate the PD patients from the healthy subjects assessed using the receiver operating characteristic curve analysis. Also, we applied our consensus and integration approach to construct a deregulated miRNA-based network in PD with the respective targets and transcription factors, and the enriched gene ontology and pathways using the enrichment analysis approach were obtained. There was a significant overexpression of miR-885 and miR-17 and the downregulation of miR-361 in the PD patients compared to the controls. The blood expression of miR-885 and miR-17 tended to increase along with the disease severity. On the other hand, the lower levels of miR-361 in the early stages of the PD patients, as compared to controls, and its higher levels in the advanced stages of PD patients, as compared to the early stages of the PD patients, were observed. Combination of all three miRNAs showed an appropriate value of AUC (0.985) to discriminate the PD patients from the healthy subjects. Also, the deregulated miRNAs were linked to the known PD pathways and the candidate related target genes were presented. We revealed 3 candidate biomarkers related to aging and cellular senescence for the first time in the patients with PD. Our in-silico analysis identified candidate target genes and TFs, including those related to neurodegeneration and PD. Overall, our findings provided novel insights into the probable age-regulatory mechanisms underlying PD and a rationale to further clarify the role of the identified miRNAs in the PD pathogenesis.

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