scholarly journals Reduced cortico-muscular beta coupling in Parkinsons disease predicts motor impairment

2021 ◽  
Author(s):  
Nahid Zokaei ◽  
Andrew J Quinn ◽  
Michele T Hu ◽  
Masud Husain ◽  
Freek van Ede ◽  
...  
Keyword(s):  
Grip Strength ◽  
Marked Reduction ◽  
Motor Impairment ◽  
Motor Symptoms ◽  
Phase Coupling ◽  
Parkinsons Disease ◽  
Novel Treatments ◽  
Healthy Control ◽  
Neural Marker ◽  
Long Range Communication

Long range communication through the motor system is thought to be facilitated by phase coupling between neural activity in the 15-30 Hz beta range. During periods of sustained muscle contraction (grip), such coupling is manifest between motor cortex and the contralateral forearm muscles, measured as the cortico-muscular coherence (CMC). We examined alterations in CMC in individuals with Parkinsons disease (PD), while equating grip strength between individuals with PD (off their medication) and healthy control participants. We show a marked reduction in beta CMC in the PD group, even though the grip strength was comparable between the two groups. Moreover, the reduced CMC was related to motor symptoms, so that individuals with lower CMC also displayed worse motor symptoms. These findings highlight the CMC as a simple, effective, and clinically relevant neural marker of PD pathology, with the potential to aid monitoring of disease progression and the efficacy of novel treatments for PD.

Motor Symptom Asymmetry Predicts Non-motor Outcome and Quality of Life Following STN DBS in Parkinson's Disease

2021 ◽  
Author(s):  
Julie Péron ◽  
Philippe Voruz ◽  
Jordan Pierce ◽  
Kévin Ahrweiller ◽  
Claire Haegelen ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Motor Symptom ◽  
Control Group ◽  
Motor Symptoms ◽  
Healthy Control ◽  
The Impact ◽  
Stn Dbs

Abstract Risk factors for long-term non-motor disorders and quality of life following subthalamic nucleus deep-brain stimulation (STN DBS) have not yet been fully identified. In the present study, we investigated the impact of motor symptom asymmetry in Parkinson’s disease.Data were extracted for 52 patients with Parkinson’s disease (half with left-sided motor symptoms and half with right-sided ones) who underwent bilateral STN and a matched healthy control group. Performances for cognitive tests and neuropsychiatric and quality-of-life questionnaires at 12 months post-DBS were compared with a pre-DBS baseline. Results indicated a deterioration in cognitive performance post-DBS in patients with left-sided motor symptoms. Performances of patients with right-sided motor symptoms were maintained, except for a verbal executive task. These differential effects had an impact on patients’ quality of life. The results highlight the existence of two distinct cognitive profiles of Parkinson’s disease, depending on motor symptom asymmetry. This asymmetry is a potential risk factor for non-motor adverse effects following STN DBS.

scholarly journals A Monoiodotyrosine Challenge Test in a Parkinson’s Disease Model

Acta Naturae ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 106-109
Author(s):  
Alexander R. Kim ◽  
Ekaterina N. Pavlova ◽  
Viktor E. Blokhin ◽  
Vsevolod V. Bogdanov ◽  
Michael V. Ugrumov
Keyword(s):  
Mouse Model ◽  
Disease Model ◽  
Challenge Test ◽  
Motor Impairment ◽  
Striatal Dopamine ◽  
Diagnostic Challenge ◽  
Parkinsons Disease ◽  
Experimental Mouse Model ◽  
Experimental Mouse ◽  
Preclinical Diagnosis

Early (preclinical) diagnosis of Parkinsons disease (PD) is a major challenge in modern neuroscience. The objective of this study was to experimentally evaluate a diagnostic challenge test with monoiodotyrosine (MIT), an endogenous inhibitor of tyrosine hydroxylase. Striatal dopamine was shown to decrease by 34% 2 h after subcutaneous injection of 100 mg/kg MIT to intact mice, with the effect not being amplified by a further increase in the MIT dose. The selected MIT dose caused motor impairment in a neurotoxic mouse model of preclinical PD, but not in the controls. This was because MIT reduced striatal dopamine to the threshold of motor symptoms manifestation only in PD mice. Therefore, using the experimental mouse model of preclinical PD, we have shown that a MIT challenge test may be used to detect latent nigrostriatal dysfunction.

Emotion Regulation Choice in Internet Addiction: Less Reappraisal, Lower Frontal Alpha Asymmetry

2021 ◽  
pp. 155005942110564
Author(s):  
Xinyu Yan ◽  
Wei Gao ◽  
Jiemin Yang ◽  
Jiajin Yuan
Keyword(s):  
Emotion Regulation ◽  
Internet Addiction ◽  
Emotional Intensity ◽  
Alpha Asymmetry ◽  
Difficulties In Emotion Regulation ◽  
Frontal Alpha Asymmetry ◽  
Healthy Control ◽  
Emotion Regulation Strategy ◽  
Regulation Strategies ◽  
Neural Marker

Individuals with internet addiction (IA) show difficulties in emotion regulation. However, they could effectively employ emotion regulation strategies when instructed. We speculate that this discrepancy might be caused by maladaptive emotion regulation choices. Recent studies indicated that decreased activity of the left frontal cortex could be a neural marker of reappraisal use. To address this problem, individuals with IA ( n = 17, IA group) and healthy individuals ( n = 23, healthy control [HC] group) were required to choose an emotion regulation strategy between reappraisal and distraction to regulate their emotions varying in emotional intensity and valence. We also compared the resting state frontal alpha asymmetry (FAA) of these 2 groups. The results replicated more choices of reappraisal in low- versus high-intensity emotional contexts across groups. More importantly, the IA group chose reappraisal less frequently compared with the HC group, irrespective of emotional intensity. Furthermore, we found individuals with IA have lower FAA than healthy controls, and FAA shows a positive correlation with the use of reappraisal. These findings suggest that IA alters individuals’ patterns of emotion regulation choice and impairs frontal activities, causing difficulties in emotion regulation.

092 Effect of the dual orexin receptor antagonist (DORA) daridorexant on behaviour upon awakening in rats and dogs

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A38-A39
Author(s):  
Giorgio Bergamini ◽  
Catherine Roch ◽  
Sean Durkin ◽  
Michel Steiner
Keyword(s):  
Grip Strength ◽  
Motor Skills ◽  
Muscle Weakness ◽  
Motor Behavior ◽  
Motor Impairment ◽  
Phase Behaviour ◽  
Fine Motor ◽  
Dependent Manner ◽  
The Impact ◽  
Time Point

Abstract Introduction The ability to be fast alert and to interact with the environment without motor impairment upon waking up, is a critical feature of natural sleep. DORAs represent a new class of insomnia medications that specifically inhibit the wake-promoting effects of orexin neuropeptides. Daridorexant is a potent and selective DORA under late stage development for the treatment of insomnia. Here, we assessed the impact of sleep-promoting doses of daridorexant on rats’ and dogs’ behaviour upon forced awakening. Zolpidem (a positive GABAA receptor modulator) was used as active comparator in rats because of its known negative impact on motor functions. Methods Rats were woken up at different time points after oral administration of daridorexant (10, 30, 100 mg/kg) or zolpidem (30, 100 mg/kg) during their inactive phase, and repeatedly subjected to two motor tasks: 1) the rotating rod test (lasting 120 sec, at each time point) assessing gross motor skills and coordination, and 2) the forepaw grip strength test assessing fine motor skills and muscle strength. Dogs were presented with food as an external, salient stimulus, three hours after administration of daridorexant in gelatin capsules (10, 30 or 90 mg/dog) during their active phase. Behaviour and signs of muscle weakness, after having woken up, were assessed by manual inspection of video recordings and concomitant electroencephalogram/electromyogram recordings. Results In both the rotarod and grip tests, daridorexant treatment had no effect on motor behavior at any dose or time point tested, while zolpidem significantly reduced the time spent on the rotarod and the grip strength in a dose and time-dependent manner (N=12/group; p<0.001;) (e.g. at 30 min post-dose, time spent on the rotarod was 84, 79–89 and 10–19 sec for vehicle, daridorexant and zolpidem, respectively). Dogs treated with daridorexant were able to wake up easily upon food presentation. They behaved and ate normally and did not show any signs of muscle weakness. Conclusion The type of sleep promoted by daridorexant is surmountable in rats and dogs and similar to physiological sleep. It allows animals to easily wake up, to behave normally without motor impairment and to respond efficiently to the environmental conditions. Support (if any) Funded by Idorsia Pharmaceuticals Ltd

scholarly journals Web-Based Assessment of Visual and Visuospatial Symptoms in Parkinson’s Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-7
Author(s):  
Melissa M. Amick ◽  
Ivy N. Miller ◽  
Sandy Neargarder ◽  
Alice Cronin-Golomb
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Construct Validity ◽  
Daily Living ◽  
Motor Symptoms ◽  
Web Based ◽  
Visuospatial Cognition ◽  
Healthy Control ◽  
Paper Format ◽  
The Web

Visual and visuospatial dysfunction is prevalent in Parkinson’s disease (PD). To promote assessment of these often overlooked symptoms, we adapted the PD Vision Questionnaire for Internet administration. The questionnaire evaluates visual and visuospatial symptoms, impairments in activities of daily living (ADLs), and motor symptoms. PD participants of mild to moderate motor severity (n=24) and healthy control participants (HC,n=23) completed the questionnaire in paper and web-based formats. Reliability was assessed by comparing responses across formats. Construct validity was evaluated by reference to performance on measures of vision, visuospatial cognition, ADLs, and motor symptoms. The web-based format showed excellent reliability with respect to the paper format for both groups (allP′s<0.001; HC completing the visual and visuospatial section only). Demonstrating the construct validity of the web-based questionnaire, self-rated ADL and visual and visuospatial functioning were significantly associated with performance on objective measures of these abilities (allP′s<0.01). The findings indicate that web-based administration may be a reliable and valid method of assessing visual and visuospatial and ADL functioning in PD.

scholarly journals Single Nuclei Sequencing of Human Putamen Oligodendrocytes Reveals Altered Heterogeneity and Disease-Associated Changes in Parkinson's Disease and Multiple System Atrophy

2021 ◽  
Author(s):  
Erin Teeple ◽  
Pooja Joshi ◽  
Rahul S. Pande ◽  
Yinyin Huang ◽  
Akshat Karambe ◽  
...  
Keyword(s):  
Multiple System Atrophy ◽  
Functional Enrichment ◽  
Cell Level ◽  
Parkinsons Disease ◽  
Unfolded Protein ◽  
Pathway Gene ◽  
Healthy Control ◽  
Protein Response ◽  
New Strategies

The role of oligodendrocytes in neurodegenerative diseases remains incompletely understood and largely unexplored at the single cell level. We profiled 87,086 single nuclei from human brain putamen region for healthy control, Parkinsons Disease (PD), and Multiple System Atrophy (MSA). Oligodendrocyte lineage cells were the dominant cell-type in the putamen with oligodendrocyte subpopulations clustered by transcriptomic variation found to exhibit diverse functional enrichment patterns, and this oligodendrocyte heterogeneity was altered in a disease-specific way. Among profiled oligodendrocyte subpopulations, differences in expression of SNCA, HAPLN2, MAPT, APP, and OPALIN were observed for PD and MSA compared with healthy controls. Intriguingly, greater activation of unfolded protein response pathway gene expression was observed in PD nuclei versus MSA. Using network analysis, we then identified specific PD- and MSA-correlated gene co-expression modules enriched with disease relevant pathways; the PD-correlated module was significantly enriched for Parkinsons Disease GWAS loci (p = 0.01046). Our analysis provides a broader understanding of oligodendrocyte heterogeneity and reveals distinctive oligodendrocyte pathological alterations associated with PD and MSA which may suggest potential novel therapeutic targets and new strategies for disease modification.

scholarly journals Multiomics implicate gut microbiota in altered lipid and energy metabolism in Parkinsons disease

2021 ◽  
Author(s):  
Pedro Alexandre Pereira ◽  
Drupad Trivedi ◽  
Justin Silverman ◽  
Ilhan Duru ◽  
Lars K Paulin ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Bacterial Community ◽  
Bacterial Community Composition ◽  
Control Groups ◽  
Parkinsons Disease ◽  
Clinical Variables ◽  
Metabolite Profiles ◽  
Healthy Control ◽  
And Control ◽  
Altered Lipid

We aimed to investigate the link between serum metabolites, gut bacterial community composition, and clinical variables in Parkinsons disease (PD) and healthy control subjects (HC). 139 metabolite features were found to be differentially abundant between the PD and Control groups. No associations were found between metabolite features and within-PD clinical variables. The results suggest alterations in serum metabolite profiles in PD, and the results of correlation analysis between metabolite features and microbiota suggest that several bacterial taxa are associated with altered lipid and energy metabolism in PD.

scholarly journals Do movement-related beta oscillations change after stroke?

2014 ◽  
Vol 112 (9) ◽  
pp. 2053-2058 ◽  
Author(s):  
Holly E. Rossiter ◽  
Marie-Hélène Boudrias ◽  
Nick S. Ward
Keyword(s):  
Motor Cortex ◽  
Primary Motor Cortex ◽  
Motor Impairment ◽  
Beta Band ◽  
Beta Oscillations ◽  
Dependent Plasticity ◽  
Control Subjects ◽  
Cortical Oscillations ◽  
Hand Grip ◽  
Healthy Control

Stroke is the most common cause of physical disability in the world today. While the key element of rehabilitative therapy is training, there is currently much interest in approaches that “prime” the primary motor cortex to be more excitable, thereby increasing the likelihood of experience-dependent plasticity. Cortical oscillations reflect the balance of excitation and inhibition, itself a key determinant of the potential for experience-dependent plasticity. In the motor system, beta-band oscillations are important and are thought to maintain the resting sensorimotor state. Here we examined motor cortex beta oscillations during rest and unimanual movement in a group of stroke patients and healthy control subjects, using magnetoencephalography. Movement-related beta desynchronization (MRBD) in contralateral primary motor cortex was found to be significantly reduced in patients compared with control subjects. Within the patient group, smaller MRBD was seen in those with more motor impairment. We speculate that impaired modulation of beta oscillations during affected hand grip is detrimental to motor control, highlighting this as a potential therapeutic target in neurorehabilitation.

scholarly journals Two Distinct Clinical Phenotypes of Bulbar Motor Impairment in Amyotrophic Lateral Sclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Kaila L. Stipancic ◽  
Yana Yunusova ◽  
Thomas F. Campbell ◽  
Jun Wang ◽  
James D. Berry ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Impairment ◽  
Motor Neuron Diseases ◽  
Clinical Scales ◽  
Syllable Repetition ◽  
Healthy Control ◽  
Clinical Variants ◽  
Function Group ◽  
Clinical Measures ◽  
Lateral Sclerosis

Objective: Understanding clinical variants of motor neuron diseases such as amyotrophic lateral sclerosis (ALS) is critical for discovering disease mechanisms and across-patient differences in therapeutic response. The current work describes two clinical subgroups of patients with ALS that, despite similar levels of bulbar motor involvement, have disparate clinical and functional speech presentations.Methods: Participants included 47 healthy control speakers and 126 speakers with ALS. Participants with ALS were stratified into three clinical subgroups (i.e., bulbar asymptomatic, bulbar symptomatic high speech function, and bulbar symptomatic low speech function) based on clinical metrics of bulbar motor impairment. Acoustic and lip kinematic analytics were derived from each participant's recordings of reading samples and a rapid syllable repetition task. Group differences were reported on clinical scales of ALS and bulbar motor severity and on multiple speech measures.Results: The high and low speech-function subgroups were found to be similar on many of the dependent measures explored. However, these two groups were differentiated on the basis of an acoustic measure used as a proxy for tongue movement.Conclusion: This study supports the hypothesis that high and low speech-function subgroups do not differ solely in overall severity, but rather, constitute two distinct bulbar motor phenotypes. The findings suggest that the low speech-function group exhibited more global involvement of the bulbar muscles than the high speech-function group that had relatively intact lingual function. This work has implications for clinical measures used to grade bulbar motor involvement, suggesting that a single bulbar measure is inadequate for capturing differences among phenotypes.

scholarly journals Association of GBA Genotype with Motor and Functional Decline in Newly Diagnosed Patients with Parkinsons Disease

Neurology ◽  
2020 ◽  
pp. 10.1212/WNL.0000000000011411
Author(s):  
Jodi Maple-Grødem ◽  
Ingvild Dalen ◽  
Ole-Bjørn Tysnes ◽  
Angus Donald Macleod ◽  
Lars Forsgren ◽  
...  
Keyword(s):  
Daily Living ◽  
Fixed Effects ◽  
Rating Scale ◽  
Functional Decline ◽  
Motor Impairment ◽  
Population Based ◽  
European Population ◽  
Carrier Status ◽  
Parkinsons Disease ◽  
Clinical Trial Designs

Objectives:To establish the significance of GBA-carrier status on motor impairment in a large cohort of patients with incident Parkinson’s disease (PD).Methods:Three European population-based studies followed 528 patients with PD from diagnosis. 440 with genomic DNA from baseline were assessed for GBA variants. We evaluated motor and functional impairment annually using the Unified PD Rating Scale (UPDRS) motor and Activity of Daily Living (ADL) sections. Differential effects of classes of GBA variants on disease progression were evaluated using mixed random and fixed effects models.Results:387 idiopathic patients (age at baseline 70.3±9.5 years; 60.2% male) and 53 GBA-carriers (age at baseline 66.8±10.1 years; 64.2% male) were included. The motor profile of the groups was clinically indistinguishable at diagnosis. GBA-carriers showed faster annual increase in UPDRS scores measuring ADL (1.5 points per year, 95% CI 1.1 to 2.0) and motor symptoms (2.2 points per year, 95% CI 1.3 to 3.1) compared to non-carriers (ADL, 1.0 points per year, 95% CI 0.9 to 1.1, P = 0.003; motor, 1.3 points per year, 95% CI 1.1 to 1.6, P = 0.007). Simulations of clinical trial designs showed that recruiting only GBA-carriers can reduce trial size by up to 65% compared to a trial recruiting all patients with PD.Conclusion:GBA variants are linked to a more aggressive motor disease course over seven years from diagnosis in patients with PD. A better understanding of PD progression in genetic subpopulations may improve disease management and has direct implications for improving the design of clinical trials.

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