Sensory attenuation is related to dopamine dose in Parkinson’s disease

ABSTRACTAbnormal initiation and control of voluntary movements are among the principal manifestations of Parkinson’s disease (PD). However, the processes underlying these abnormalities and their potential remediation by dopamine treatment remain poorly understood. Normally, movements depend on the integration of sensory information with the predicted consequences of action. This integration leads to a suppression in the intensity of predicted sensations, and increases the relative salience of unexpected stimuli to facilitate the control of movements. We examined this integration process and its relation to dopamine in PD, by measuring sensorimotor attenuation – the reduction in the perceived intensity of predicted sensations from self-generated versus external actions. Patients with idiopathic PD (n=18) and population-derived controls (n=175) matched a set of target forces applied to their left index finger by a torque motor. To match the force, participants either pressed with their right index finger (‘Direct’ condition) or used a linear potentiometer that controlled a motor (‘Slider’ condition). We found that despite changes in sensitivity to different forces, overall sensory attenuation did not differ between medicated PD patients and controls. Importantly, the degree of attenuation was negatively related to PD motor severity but positively related to individual patient dopamine dose, as measured by levodopa dose equivalency. The results suggest that dopamine could regulate the integration of sensorimotor prediction with sensory information to facilitate the control of voluntary movements.

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Sensory Attenuation in Sport and Rehabilitation: Perspective from Research in Parkinson’s Disease

Brain Sciences ◽

10.3390/brainsci11050580 ◽

2021 ◽

Vol 11 (5) ◽

pp. 580

Author(s):

Joshua Kearney ◽

John-Stuart Brittain

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Sensory Input ◽

Contextual Information ◽

Sensory Information ◽

Complex Environments ◽

Contextual Cues ◽

Task Relevance ◽

Sensory Attenuation

People with Parkinson’s disease (PD) experience motor symptoms that are affected by sensory information in the environment. Sensory attenuation describes the modulation of sensory input caused by motor intent. This appears to be altered in PD and may index important sensorimotor processes underpinning PD symptoms. We review recent findings investigating sensory attenuation and reconcile seemingly disparate results with an emphasis on task-relevance in the modulation of sensory input. Sensory attenuation paradigms, across different sensory modalities, capture how two identical stimuli can elicit markedly different perceptual experiences depending on our predictions of the event, but also the context in which the event occurs. In particular, it appears as though contextual information may be used to suppress or facilitate a response to a stimulus on the basis of task-relevance. We support this viewpoint by considering the role of the basal ganglia in task-relevant sensory filtering and the use of contextual signals in complex environments to shape action and perception. This perspective highlights the dual effect of basal ganglia dysfunction in PD, whereby a reduced capacity to filter task-relevant signals harms the ability to integrate contextual cues, just when such cues are required to effectively navigate and interact with our environment. Finally, we suggest how this framework might be used to establish principles for effective rehabilitation in the treatment of PD.

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Study of cognitive impairment and genetic polymorphism of SLC41A1 (rs11240569 allele) in Parkinson’s disease in Upper Egypt: case-control study

The Egyptian Journal of Neurology Psychiatry and Neurosurgery ◽

10.1186/s41983-021-00341-0 ◽

2021 ◽

Vol 57 (1) ◽

Author(s):

Hamdy N. El-Tallawy ◽

Tahia H. Saleem ◽

Wafaa M. Farghaly ◽

Heba Mohamed Saad Eldien ◽

Ashraf Khodaery ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Case Control Study ◽

Case Control ◽

Control Group ◽

Motor Symptoms ◽

And Control ◽

Non Motor Symptoms ◽

Control Study

Abstract Background Parkinson’s disease is one of the neurodegenerative disorders that is caused by genetic and environmental factors or interaction between them. Solute carrier family 41 member 1 within the PARK16 locus has been reported to be associated with Parkinson’s disease. Cognitive impairment is one of the non-motor symptoms that is considered a challenge in Parkinson’s disease patients. This study aimed to investigate the association of rs11240569 polymorphism; a synonymous coding variant in SLC41A1 in Parkinson’s disease patients in addition to the assessment of cognitive impairment in those patients. Results In a case -control study, rs11240569 single nucleotide polymorphisms in SLC41A1, genes were genotyped in 48 Parkinson’s disease patients and 48 controls. Motor and non-motor performance in Parkinson's disease patients were assessed by using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). The genotype and allele frequencies were compared between the two groups and revealed no significant differences between case and control groups for rs11240569 in SLC41A1 gene with P value .523 and .54, respectively. Cognition was evaluated and showed the mean ± standard deviation (SD) of WAIS score of PD patients 80.4 ± 9.13 and the range was from 61 to 105, in addition to MMSE that showed mean ± SD 21.96 ± 3.8. Conclusion Genetic testing of the present study showed that rs11240569 polymorphism of SLC41A1 gene has no significant differences in distributions of alleles and genotypes between cases and control group, in addition to cognitive impairment that is present in a large proportion of PD patients and in addition to the strong correlation between cognitive impairment and motor and non-motor symptoms progression.

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Imaging mass cytometry reveals generalised deficiency in OXPHOS complexes in Parkinson’s disease

npj Parkinson s Disease ◽

10.1038/s41531-021-00182-x ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Chun Chen ◽

David McDonald ◽

Alasdair Blain ◽

Ashwin Sachdeva ◽

Laura Bone ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Oxidative Phosphorylation ◽

Mitochondrial Dysfunction ◽

Mitochondrial Disease ◽

Dopaminergic Neurons ◽

Neuronal Response ◽

Proteomic Profiling ◽

Mass Cytometry ◽

And Control

AbstractHere we report the application of a mass spectrometry-based technology, imaging mass cytometry, to perform in-depth proteomic profiling of mitochondrial complexes in single neurons, using metal-conjugated antibodies to label post-mortem human midbrain sections. Mitochondrial dysfunction, particularly deficiency in complex I has previously been associated with the degeneration of dopaminergic neurons in Parkinson’s disease. To further our understanding of the nature of this dysfunction, and to identify Parkinson’s disease specific changes, we validated a panel of antibodies targeting subunits of all five mitochondrial oxidative phosphorylation complexes in dopaminergic neurons from Parkinson’s disease, mitochondrial disease, and control cases. Detailed analysis of the expression profile of these proteins, highlighted heterogeneity between individuals. There is a widespread decrease in expression of all complexes in Parkinson’s neurons, although more severe in mitochondrial disease neurons, however, the combination of affected complexes varies between the two groups. We also provide evidence of a potential neuronal response to mitochondrial dysfunction through a compensatory increase in mitochondrial mass. This study highlights the use of imaging mass cytometry in the assessment and analysis of expression of oxidative phosphorylation proteins, revealing the complexity of deficiencies of these proteins within individual neurons which may contribute to and drive neurodegeneration in Parkinson’s disease.

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Blood Exosomes Have Neuroprotective Effects in a Mouse Model of Parkinson’s Disease

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/3807476 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14

Author(s):

Ting Sun ◽

Zhe-Xu Ding ◽

Xin Luo ◽

Qing-Shan Liu ◽

Yong Cheng

Keyword(s):

Oxidative Stress ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Amino Acid ◽

Dopaminergic Neurons ◽

Motor Coordination ◽

Oxidized Lipids ◽

Metabolomic Analysis ◽

Neuroprotective Effects ◽

And Control

Parkinson’s disease (PD) is a common and complex neurodegenerative disease; the pathogenesis of which is still uncertain. Exosomes, nanosized extracellular vesicles, have been suggested to participate in the pathogenesis of PD, but their role is unknown. Here, a metabolomic analysis of serum and brain exosomes showed differentially expressed metabolites between 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride- (MPTP-) induced PD mice and control mice, such as oxidized lipids, vitamins, and cholesterol. These metabolites were enriched in coenzyme, nicotinamide, and amino acid pathways related to PD, and they could be served as preclinical biomarkers. We further found that blood-derived exosomes from healthy volunteers alleviated impaired motor coordination in MPTP-treated mice. Results from immunohistochemistry and western blotting indicated that the loss of dopaminergic neurons in substantia nigra and striatum of PD model mice was rescued by the exosome treatment. The exosome treatment also restored the homeostasis of oxidative stress, neuroinflammation, and cell apoptosis in the model mice. These results suggest that exosomes are important mediators for PD pathogenesis, and exosomes are promising targets for the diagnosis and treatment of PD.

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Predicting Parkinson’s Disease Medication Regimen Using Sensor Technology

10.21203/rs.3.rs-198765/v1 ◽

2021 ◽

Author(s):

Jeremy Watts ◽

Anahita Khojandi ◽

Rama Vasudevan ◽

Fatta B. Nahab ◽

Ritesh Ramdhani

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Random Forest ◽

Classification Model ◽

Sensor Data ◽

Sensor Technology ◽

Medication Regimen ◽

Levodopa Dose ◽

Subjective Data ◽

Random Forest Classification

Abstract Parkinson’s disease (PD) medication treatment planning is generally based on subjective data through in-office, physicianpatient interactions. The Personal KinetiGraphTM (PKG) has shown promise in enabling objective, continuous remote health monitoring for Parkinson’s patients. In this proof-of-concept study, we propose to use objective sensor data from the PKG and apply machine learning to subtype patients based on levodopa regimens and response. We apply k-means clustering to a dataset of with-in-subject Parkinson’s medication changes—clinically assessed by the PKG and Hoehn & Yahr (H&Y) staging. A random forest classification model was then used to predict patients’ cluster allocation based on their respective PKG data and demographic information. Clinically relevant clusters were developed based on longitudinal dopaminergic regimens—partitioned by levodopa dose, administration frequency, and total levodopa equivalent daily dose—with the PKG increasing cluster granularity compared to the H&Y staging. A random forest classifier was able to accurately classify subjects of the two most demographically similar clusters with an accuracy of 87:9 ±1:3

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Deficits in monitoring self-produced speech in Parkinson’s disease

10.1101/823674 ◽

2019 ◽

Cited By ~ 1

Author(s):

Henry Railo ◽

Niklas Nokelainen ◽

Saara Savolainen ◽

Valtteri Kaasinen

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Neural Mechanisms ◽

Speech Impairment ◽

Self Monitoring ◽

Evoked Activity ◽

And Control ◽

N1 Wave ◽

Electrophysiological Correlate

AbstractObjectiveSpeech deficits are common in Parkinson’s disease, and behavioural findings suggest that the deficits may be due to impaired monitoring of self-produced speech. The neural mechanisms of speech deficits are not well understood. We examined a well-documented electrophysiological correlate of speech self-monitoring in patients with Parkinson’s disease and control participants.MethodsWe measured evoked electroencephalographic responses to self-produced and passively heard sounds (/a/ phonemes) in age-matched controls (N=18), and Parkinson’s disease patients who had minor speech impairment, but reported subjectively experiencing no speech deficits (N=17).ResultsDuring speaking, auditory evoked activity 100 ms after phonation (N1 wave) was less suppressed in Parkinson’s disease than controls when compared to the activity evoked by passively heard phonemes. This difference between the groups was driven by increased amplitudes to self-produced phonemes, and reduced amplitudes passively heard phonemes in Parkinson’s disease.ConclusionsThe finding indicates that auditory evoked activity is abnormally modulated during speech in Parkinson’s patients who do not subjectively notice speech impairment. This mechanism could play a role in producing speech deficits in as the disease progresses.

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CONCURRENCE OF FRAILTY AND PARKINSON’S DISEASE

Journal of Frailty & Aging ◽

10.14283/jfa.2012.20 ◽

2012 ◽

pp. 1-5

Author(s):

K.P. ROLAND ◽

K.M.D. CORNETT ◽

O. THEOU ◽

J.M. JAKOBI ◽

G.R. JONES

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cardiovascular Health ◽

Community Dwelling ◽

Health Study ◽

Cardiovascular Health Study ◽

Physical Frailty ◽

Levodopa Dose ◽

Frailty Phenotype ◽

Age Related

Background: Females with Parkinson’s disease (PD) are at greater risk of frailty than males. Little is known about how age and disease-related characteristics influence frailty in females with PD because frailty studies often exclude persons with underlying neurological pathologies. Objective: To determine age and diseaserelated characteristics that best explain physical frailty in community-dwelling females with and without PD. Design & Measurement: Correlation coefficients described relationships between PD-related characteristics and physical frailty phenotype criteria (Cardiovascular Health Study). Regression analysis identified associations between disease-related characteristics and frailty in non-PD and PD females. Setting: Community-dwelling. Participants: Females with mild to moderate PD (n = 17, mean age = 66 ± 8.5 years) and non-PD (n = 18, mean age = 72 ± 13.2 years) participated. Results: Daily carbidopa-levodopa dose best explained frailty in PD females (β = 0.5), whereas in non-PD females, age (β = 0.7) and comorbidity (β = 0.5) were most associated with frailty. Conclusions: Dopaminergic medication explained frailty in PD and not measures of disease progression (i.e. severity, duration). In females without PD age-related accumulation of comorbidities resulted in greater risk of frailty. This indicates dopaminergic management of PD symptoms may better reflect frailty in females with PD than disease severity or duration. These data suggest the influence of underlying frailty should be considered when managing neurological conditions. Understanding how frailty concurrently exists with PD and how these conditions progress within the aging female will facilitate future care management.

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Retinal Morphological Changes during the Two Years of Follow-Up in Parkinson's Disease

10.21203/rs.3.rs-17217/v1 ◽

2020 ◽

Author(s):

Mahmut Atum ◽

Bekir Enes Demiryurek

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rating Scale ◽

Early Stage ◽

Morphological Changes ◽

Fiber Layer ◽

Significant Difference ◽

Yahr Scale ◽

And Control

Abstract Background: The study aims to investigate the relationship between the progression of idiopathic Parkinson's disease (IPD) and retinal morphology. Methods: The study was carried out with 23 patients diagnosed with early-stage IPD (phases 1 and 2 of the Hoehn and Yahr scale) and 30 age-matched healthy controls. All patients were followed up at least two years, with 6-month intervals (initial, 6th month, 12th month, 18th month, and 24th month), and detailed neurological and ophthalmic examinations were performed at each follow-up. Unified Parkinson's Disease Rating Scale part III (UPDRS Part III) scores, Hoehn and Yahr (H&Y) scores, best-corrected visual acuity (BCVA), intraocular pressure (IOP) measurement, central macular thickness (CMT) and retinal nerve fiber layer (RNFL) thickness were analyzed at each visit. Results: The average age of the IPD and control groups was 43.96 ± 4.88 years, 44.53 ± 0.83 years, respectively. The mean duration of the disease in the IPD group was 7.48 ± 5.10 months at the start of the study (range 0-16). There was no statistically significant difference in BCVA and IOP values between the two groups during the two-year follow-up period (p> 0.05, p> 0.05, respectively). Average and superior quadrant RNFL thicknesses were statistically different between the two groups at 24 months and there was no significant difference between other visits (p = 0.025, p=0.034, p> 0.05, respectively). There was no statistically significant difference in CMT between the two groups during the follow-up period (p> 0.05). Conclusion: Average and superior quadrant RNFL thicknesses were significantly thinning with the progression of IPD.

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Dopaminergic Modulation of Sensory Attenuation in Parkinson's Disease: Is There an Underlying Modulation of Beta Power?

Frontiers in Neurology ◽

10.3389/fneur.2019.01001 ◽

2019 ◽

Vol 10 ◽

Author(s):

Antonella Macerollo ◽

Patricia Limousin ◽

Prasad Korlipara ◽

Tom Foltynie ◽

Mark J. Edwards ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Beta Power ◽

Dopaminergic Modulation ◽

Sensory Attenuation

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Physical Activity across Frailty Phenotypes in Females with Parkinson’s Disease

Journal of Aging Research ◽

10.1155/2012/468156 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 7

Author(s):

Kaitlyn P. Roland ◽

Kayla M. D. Cornett ◽

Olga Theou ◽

Jennifer M. Jakobi ◽

Gareth R. Jones

Keyword(s):

Physical Activity ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Self Report ◽

Physical Activity Intensity ◽

Levodopa Dose ◽

Frailty Phenotype ◽

Activity Intensity ◽

Global Positioning ◽

Reduced Physical Activity

Females with Parkinson’s disease (PD) are vulnerable to frailty. PD eventually leads to decreased physical activity, an indicator of frailty. We speculate PD results in frailty through reduced physical activity.Objective. Determine the contribution of physical activity on frailty in PD (n=15, 65 ± 9 years) and non-PD (n=15, 73 ± 14 years) females.Methods. Frailty phenotype (nonfrail/prefrail/frail) was categorized and 8 hours of physical activity was measured using accelerometer, global positioning system, and self-report. Two-way ANCOVA (age as covariate) was used to compare physical activity between disease and frailty phenotypes. Spearman correlation assessed relationships, and linear regression determined associations with frailty.Results. Nonfrail recorded more physical activity (intensity, counts, self-report) compared with frail. Self-reported physical activity was greater in PD than non-PD. In non-PD, step counts, light physical activity time, sedentary time, and self-reported physical activity were related to frailty (R=0.91). In PD, only carbidopa-levodopa dose was related to frailty (r=0.61).Conclusion. Physical activity influences frailty in females without PD. In PD females, disease management may be a better indicator of frailty than physical activity. Further investigation into how PD associated factors contribute to frailty is warranted.

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