scholarly journals Continuous force measurements reveal no inhibitory control deficits in Parkinson’s disease

2019 ◽  
Author(s):  
Jade S. Pickering ◽  
Jennifer McBride ◽  
Iracema Leroi ◽  
Ellen Poliakoff
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Inhibitory Control ◽  
Response Inhibition ◽  
Force Measurement ◽  
Button Press ◽  
Continuous Measure ◽  
Response Force ◽  
Link Type ◽  
And Control

AbstractSuppression of unwanted motor responses can be disrupted by Parkinson’s disease. People with Parkinson’s (PwP) can show maladaptive reward-driven behaviours in the form of impulse control behaviours, which are associated with use of the dopaminergic treatments used to alleviate the motor symptoms of the disease. However, the effects of Parkinson’s itself on impulsive behaviour and control are unclear – empirical studies have yielded mixed findings, and some imaging studies have shown a functional deficit in the absence of a measurable change in behaviour. Here, we investigated the effects of Parkinson’s on response activation and control by studying the dynamics of response in standard inhibitory control tasks – the Stop Signal and Simon tasks – using a continuous measure of response force. Our results are largely in favour of the conclusion that response inhibition appears to be intact in PwP, even when using a more sensitive measure of behavioural control relative to traditional button-press measures. Our findings provide some clarity as to the effects of Parkinson’s on response inhibition and show continuous response force measurement can provide a sensitive means of detecting erroneous response activity in PwP, which could also be generalised to studying related processes in other populations.Open dataData and analysis can be found on the Open Science Framework (osf.io/kx6h3/)Pre-print templateWiernik, B.M. (2019, October 11). Preprint templates. osf.io/hsv6a/

scholarly journals Continuous force measurements reveal no inhibitory control deficits in Parkinson’s disease

2020 ◽  
Vol 238 (5) ◽  
pp. 1119-1132
Author(s):  
Jade S. Pickering ◽  
Iracema Leroi ◽  
Jennifer McBride ◽  
Ellen Poliakoff
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Inhibitory Control ◽  
Response Inhibition ◽  
Force Measurement ◽  
Empirical Studies ◽  
Button Press ◽  
Continuous Measure ◽  
Response Force ◽  
And Control

Abstract Suppression of unwanted motor responses can be disrupted by Parkinson’s disease. People with Parkinson’s (PwP) can show maladaptive reward-driven behaviours in the form of impulse control behaviours, which are associated with the use of the dopaminergic treatments used to alleviate the motor symptoms of the disease. However, the effects of Parkinson’s itself on impulsive behaviour and control are unclear—empirical studies have yielded mixed findings, and some imaging studies have shown a functional deficit in the absence of a measurable change in behaviour. Here, we investigated the effects of Parkinson’s on response activation and control by studying the dynamics of response in standard inhibitory control tasks—the Stop Signal and Simon tasks—using a continuous measure of response force. Our results are largely in favour of the conclusion that response inhibition appears to be intact in PwP, even when using a more sensitive measure of behavioural control relative to traditional button-press measures. Our findings provide some clarity as to the effects of Parkinson’s on response inhibition and show continuous response force measurement can provide a sensitive means of detecting erroneous response activity in PwP, which could also be generalised to studying related processes in other populations.

scholarly journals Reduced locus coeruleus integrity linked to response inhibition deficits in parkinsonian disorders

2021 ◽  
Author(s):  
Rong Ye ◽  
Frank Hubert Hezemans ◽  
Claire O'Callaghan ◽  
Kamen A Tsvetanov ◽  
Catarina Rua ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Locus Coeruleus ◽  
Progressive Supranuclear Palsy ◽  
Inhibitory Control ◽  
Response Inhibition ◽  
Stop Signal Task ◽  
Model Parameters ◽  
Noradrenergic System ◽  
Parkinsonian Disorders

Parkinson's disease and progressive supranuclear palsy (PSP) both impair response inhibition, exacerbating impulsivity. Inhibitory control deficits vary across individuals, and have been linked with worse prognosis and lack of improvement on dopaminergic therapy. Motor and cognitive control are associated with noradrenergic innervation of the cortex, arising from the locus coeruleus noradrenergic system. Here we test the hypothesis that loss of structural integrity of the locus coeruleus explains response inhibition deficits in progressive supranuclear palsy and Parkinson's disease. This cross-sectional observational study recruited 24 people with idiopathic Parkinson's disease, 14 with PSP-Richardson's syndrome, and 24 age- and sex-matched controls. All participants undertook a stop-signal task and ultrahigh field 7T-magnetic transfer weighted imaging of the locus coeruleus. Hierarchical Bayesian estimation of the parameters of 'race models' of go- versus stop-decisions was used to quantify the cognitive processes of response inhibition. We tested the multivariate relationship between locus coeruleus integrity and model parameters using partial least squares. Both disorders impaired response inhibition at the group level. Progressive supranuclear palsy caused a distinct pattern of abnormalities in inhibitory control, relative to Parkinson's disease and healthy controls, with a paradoxically reduced threshold for go responses, but longer non-decision times, and more lapses of attention. The variation in response inhibition correlated with variation in the integrity of the locus coeruleus, across participants in both clinical groups. Structural imaging of the locus coeruleus, coupled with behavioural modelling in parkinsonian disorders, confirms that locus coeruleus integrity is associated with response inhibition and its degeneration contributes to neurobehavioural changes. The noradrenergic system is therefore a promising target to treat impulsivity in these conditions. The optimisation of noradrenergic treatment is likely to benefit from stratification according to locus coeruleus integrity.

scholarly journals Inhibitory control dysfunction in parkinsonian impulse control disorders

Brain ◽  
2020 ◽  
Author(s):  
Garance M Meyer ◽  
Charlotte Spay ◽  
Alina Beliakova ◽  
Gabriel Gaugain ◽  
Gianni Pezzoli ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Inhibitory Control ◽  
Response Inhibition ◽  
Impulse Control ◽  
Supplementary Motor Area ◽  
Impulse Control Disorders ◽  
Motor Area ◽  
Beta Activity ◽  
Visuomotor Task

Abstract Impulse control disorders (ICDs) in Parkinson’s disease have been associated with dysfunctions in the control of value- or reward-based responding (choice impulsivity) and abnormalities in mesocorticolimbic circuits. The hypothesis that dysfunctions in the control of response inhibition (action impulsivity) also play a role in Parkinson’s disease ICDs has recently been raised, but the underlying neural mechanisms have not been probed directly. We used high-resolution EEG recordings from 41 patients with Parkinson’s disease with and without ICDs to track the spectral and dynamical signatures of different mechanisms involved in inhibitory control in a simple visuomotor task involving no selection between competing responses and no reward to avoid potential confounds with reward-based decision. Behaviourally, patients with Parkinson’s disease with ICDs proved to be more impulsive than those without ICDs. This was associated with decreased beta activity in the precuneus and in a region of the medial frontal cortex centred on the supplementary motor area. The underlying dynamical patterns pinpointed dysfunction of proactive inhibitory control, an executive mechanism intended to gate motor responses in anticipation of stimulation in uncertain contexts. The alteration of the cortical drive of proactive response inhibition in Parkinson’s disease ICDs pinpoints the neglected role the precuneus might play in higher order executive functions in coordination with the supplementary motor area, specifically for switching between executive settings. Clinical perspectives are discussed in the light of the non-dopaminergic basis of this function.

Impaired Inhibitory Control During Walking in Parkinson’s Disease Patients: An EEG Study

2021 ◽  
pp. 1-14
Author(s):  
Ronen Sosnik ◽  
Shani Danziger-Schragenheim ◽  
Daniel Possti ◽  
Firas Fahoum ◽  
Nir Giladi ◽  
...  
Keyword(s):  
Older Adults ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Young Adults ◽  
Electrical Activity ◽  
Inhibitory Control ◽  
Response Inhibition ◽  
Event Related Potentials ◽  
P300 Latency ◽  
Related Potentials

Background: The performance on a visual Go/NoGo (VGNG) task during walking has been used to evaluate the effect of gait on response inhibition in young and older adults; however, no work has yet included Parkinson’s disease (PD) patients for whom such changes may be even more enhanced. Objective: In this study, we aimed to explore the effect of gait on automatic and cognitive inhibitory control phases in PD patients and the associated changes in neural activity and compared them with young and older adults. Methods: 30 PD patients, 30 older adults, and 11 young adults performed a visual Go/NoGo task in a sitting position and during walking on a treadmill while their EEG activity and gait were recorded. Brain electrical activity was evaluated by the amplitude, latency, and scalp distribution of N2 and P300 event related potentials. Mix model analysis was used to examine group and condition effects on task performance and brain activity. Results: The VGNG accuracy rates in PD patients during walking were lower than in young and older adults (F = 5.619, p = 0.006). For all groups, N2 latency during walking was significantly longer than during sitting (p = 0.013). In addition, P300 latency was significantly longer in PD patients (p <  0.001) and older adults (p = 0.032) during walking compared to sitting and during ‘NoGo’ trials compared with ‘Go’ trials. Moreover, the young adults showed the smallest number of electrodes for which a significant differential activation between sit to walk was observed, while PD patients showed the largest with N2 being more strongly manifested in bilateral parietal electrodes during walking and in frontocentral electrodes while seated. Conclusion: The results show that response inhibition during walking is impaired in older subjects and PD patients and that increased cognitive load during dual-task walking relates to significant change in scalp electrical activity, mainly in parietal and frontocentral channels.

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

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.

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

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.

scholarly journals Exenatide once weekly over 2 years as a potential disease-modifying treatment for Parkinson’s disease: protocol for a multicentre, randomised, double blind, parallel group, placebo controlled, phase 3 trial: The ‘Exenatide-PD3’ study

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e047993
Author(s):  
Nirosen Vijiaratnam ◽  
Christine Girges ◽  
Grace Auld ◽  
Marisa Chau ◽  
Kate Maclagan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Primary Outcome ◽  
Phase 3 ◽  
Double Blind ◽  
Treatment Groups ◽  
Link Type ◽  
South Central ◽  
Disease Modifying ◽  
Secondary Outcomes

IntroductionParkinson’s disease (PD) is a common neurodegenerative disorder with substantial morbidity. No disease-modifying treatments currently exist. The glucagon like peptide-1 receptor agonist exenatide has been associated in single-centre studies with reduced motor deterioration over 1 year. The aim of this multicentre UK trial is to confirm whether these previous positive results are maintained in a larger number of participants over 2 years and if effects accumulate with prolonged drug exposure.Methods and analysisThis is a phase 3, multicentre, double-blind, randomised, placebo-controlled trial of exenatide at a dose of 2 mg weekly in 200 participants with mild to moderate PD. Treatment duration is 96 weeks. Randomisation is 1:1, drug to placebo. Assessments are performed at baseline, week 12, 24, 36, 48, 60, 72, 84 and 96 weeks.The primary outcome is the comparison of Movement Disorders Society Unified Parkinson’s Disease Rating Scale part 3 motor subscore in the practically defined OFF medication state at 96 weeks between participants according to treatment allocation. Secondary outcomes will compare the change between groups among other motor, non-motor and cognitive scores. The primary outcome will be reported using descriptive statistics and comparisons between treatment groups using a mixed model, adjusting for baseline scores. Secondary outcomes will be summarised between treatment groups using summary statistics and appropriate statistical tests to assess for significant differences.Ethics and disseminationThis trial has been approved by the South Central-Berkshire Research Ethics Committee and the Health Research Authority. Results will be disseminated in peer-reviewed journals, presented at scientific meetings and to patients in lay-summary format.Trial registration numbersNCT04232969, ISRCTN14552789.

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

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.

scholarly journals Allelic variant in SLC6A3 rs393795 affects cerebral regional homogeneity and gait dysfunction in patients with Parkinson’s disease

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7957
Author(s):  
Lina Wang ◽  
Yongsheng Yuan ◽  
Jianwei Wang ◽  
Yuting Shen ◽  
Yan Zhi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Allelic Variation ◽  
Inferior Frontal Gyrus ◽  
Freezing Of Gait ◽  
Clinical Manifestations ◽  
Regional Homogeneity ◽  
Allelic Variant ◽  
Analysis Of Covariance ◽  
Link Type

Aims We sought to explore the role of the SLC6A3 rs393795 allelic variant in cerebral spontaneous activity and clinical features in Parkinson’s disease (PD) via imaging genetic approach. Methods Our study recruited 50 PD and 45 healthy control (HC) participants to provide clinical, genetic, and resting state functional magnetic resonance imaging (rs-fMRI) data. All subjects were separated into 16 PD-AA, 34 PD-CA/CC, 14 HC-AA, and 31 HC-CA/CC four subgroups according to SLC6A3 rs393795 genotyping. Afterwards, main effects and interactions of groups (PD versus HC) and genotypes (AA versus CA/CC) on cerebral function reflected by regional homogeneity (ReHo) were explored using two-way analysis of covariance (ANCOVA) after controlling age and gender. Finally, Spearman’ s correlations were employed to investigate the relationships between significantly interactive brain regions and clinical manifestations in PD subgroups. Results Compared with HC subjects, PD patients exhibited increased ReHo signals in left middle temporal gyrus and decreased ReHo signals in left pallidum. Compared with CA/CC carriers, AA genotype individuals showed abnormal increased ReHo signals in right inferior frontal gyrus (IFG) and supplementary motor area (SMA). Moreover, significant interactions (affected by both disease factor and allelic variation) were detected in right inferior temporal gyrus (ITG). Furthermore, aberrant increased ReHo signals in right ITG were observed in PD-AA in comparison with PD-CA/CC. Notably, ReHo values in right ITG were negatively associated with Tinetti Mobility Test (TMT) gait subscale scores and positively related to Freezing of Gait Questionnaire (FOG-Q) scores in PD-AA subgroup. Conclusions Our findings suggested that SLC6A3 rs393795 allelic variation might have a trend to aggravate the severity of gait disorders in PD patients by altering right SMA and IFG function, and ultimately result in compensatory activation of right ITG. It could provide us with a new perspective for exploring deeply genetic mechanisms of gait disturbances in PD.

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

2019 ◽  
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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