scholarly journals Impaired Desynchronization of Beta Activity Underlies Memory Deficits in People with Parkinson’s Disease

2019 ◽  
Author(s):  
Hayley J. MacDonald ◽  
John-Stuart Brittain ◽  
Bernhard Spitzer ◽  
Simon Hanslmayr ◽  
Ned Jenkinson
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Brain Activity ◽  
Memory Performance ◽  
Memory Formation ◽  
Motor Deficits ◽  
Beta Activity ◽  
Memory Encoding ◽  
Concomitant Reduction ◽  
Non Motor Symptoms

AbstractThere is a pressing need to better understand the mechanisms underpinning the increasingly recognised non-motor deficits in Parkinson’s disease. Brain activity during Parkinson’s disease is excessively synchronized within the beta range (12–30Hz). However, relatively little is known about how the abnormal beta rhythms impact on non-motor symptoms. In healthy adults, beta desynchronization is necessary for successful episodic memory formation. We investigated whether there was a direct relationship between decreased beta modulation and memory formation in Parkinson’s disease. Electroencephalography recordings were made during an established memory-encoding paradigm. Parkinson’s participants showed impaired memory strength (P = 0.023) and reduced beta desynchronization (P = 0.014) relative to controls. Longer disease duration was correlated with a larger reduction in beta desynchronization, and a concomitant reduction in memory performance. These novel results extend the notion that pathological beta activity is causally implicated in the motor and (lesser appreciated) non-motor deficits inherent to Parkinson’s disease.

scholarly journals Memory deficits in Parkinson’s disease are associated with reduced beta power modulation

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Hayley J MacDonald ◽  
John-Stuart Brittain ◽  
Bernhard Spitzer ◽  
Simon Hanslmayr ◽  
Ned Jenkinson
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Duration ◽  
Memory Formation ◽  
Motor Deficits ◽  
Beta Activity ◽  
Motor Symptoms ◽  
Memory Encoding ◽  
Beta Power ◽  
Non Motor Symptoms

Abstract There is an increasing recognition of the significant non-motor symptoms that burden people with Parkinson’s disease. As such, there is a pressing need to better understand and investigate the mechanisms underpinning these non-motor deficits. The electrical activity within the brains of people with Parkinson’s disease is known to exhibit excessive power within the beta range (12–30 Hz), compared with healthy controls. The weight of evidence suggests that this abnormally high level of beta power is the cause of bradykinesia and rigidity in Parkinson’s disease. However, less is known about how the abnormal beta rhythms seen in Parkinson’s disease impact on non-motor symptoms. In healthy adults, beta power decreases are necessary for successful episodic memory formation, with greater power decreases during the encoding phase predicting which words will subsequently be remembered. Given the raised levels of beta activity in people with Parkinson’s disease, we hypothesized that the necessary decrease in power during memory encoding would be diminished and that this would interfere with episodic memory formation. Accordingly, we conducted a cross-sectional, laboratory-based experimental study to investigate whether there was a direct relationship between decreased beta modulation and memory formation in Parkinson’s disease. Electroencephalography recordings were made during an established memory-encoding paradigm to examine brain activity in a cohort of adults with Parkinson’s disease (N = 28, 20 males) and age-matched controls (N = 31, 18 males). The participants with Parkinson’s disease were aged 65 ± 6 years, with an average disease duration of 6 ± 4 years, and tested on their normal medications to avoid the confound of exacerbated motor symptoms. Parkinson’s disease participants showed impaired memory strength (P = 0.023) and reduced beta power decreases (P = 0.014) relative to controls. Longer disease duration was correlated with a larger reduction in beta modulation during encoding, and a concomitant reduction in memory performance. The inability to sufficiently decrease beta activity during semantic processing makes it a likely candidate to be the central neural mechanism underlying this type of memory deficit in Parkinson’s disease. These novel results extend the notion that pathological beta activity is causally implicated in the motor and (lesser appreciated) non-motor deficits inherent to Parkinson’s disease. These findings provide important empirical evidence that should be considered in the development of intelligent next-generation therapies.

scholarly journals The Add-On Effect of Lactobacillus plantarum PS128 in Patients With Parkinson's Disease: A Pilot Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Chin-Song Lu ◽  
Hsiu-Chen Chang ◽  
Yi-Hsin Weng ◽  
Chiung-Chu Chen ◽  
Yi-Shan Kuo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lactobacillus Plantarum ◽  
Outcome Measures ◽  
Rating Scale ◽  
Controlled Trial ◽  
Secondary Outcome ◽  
Motor Deficits ◽  
Motor Symptoms ◽  
Non Motor Symptoms

Background:Lactobacillus plantarum PS128 (PS128) is a specific probiotic, known as a psychobiotic, which has been demonstrated to alleviate motor deficits and inhibit neurodegenerative processes in Parkinson's disease (PD)-model mice. We hypothesize that it may also be beneficial to patients with PD based on the possible mechanism via the microbiome-gut-brain axis.Methods: This is an open-label, single-arm, baseline-controlled trial. The eligible participants were scheduled to take 60 billion colony-forming units of PS128 once per night for 12 weeks. Clinical assessments were conducted using the Unified Parkinson's Disease Rating Scale (UPDRS), modified Hoehn and Yahr scale, and change in patient “ON-OFF” diary recording as primary outcome measures. The non-motor symptoms questionnaire, Beck depression inventory-II, patient assessment of constipation symptom, 39-item Parkinson's Disease Questionnaire (PDQ-39), and Patient Global Impression of Change (PGI-C) were assessed as secondary outcome measures.Results: Twenty-five eligible patients (32% women) completed the study. The mean age was 61.84 ± 5.74 years (range, 52–72), mean disease duration was 10.12 ± 2.3 years (range, 5–14), and levodopa equivalent daily dosage was 1063.4 ± 209.5 mg/daily (range, 675–1,560). All patients remained on the same dosage of anti-parkinsonian and other drugs throughout the study. After 12 weeks of PS128 supplementation, the UPDRS motor scores improved significantly in both the OFF and ON states (p = 0.004 and p = 0.007, respectively). In addition, PS128 intervention significantly improved the duration of the ON period and OFF period as well as PDQ-39 values. However, no obvious effect of PS128 on non-motor symptoms of patients with PD was observed. Notably, the PGI-C scores improved in 17 patients (68%). PS128 intervention was also found to significantly reduce plasma myeloperoxidase and urine creatinine levels.Conclusion: The present study demonstrated that PS128 supplementation for 12 weeks with constant anti-parkinsonian medication improved the UPDRS motor score and quality of life of PD patients. We suggest that PS128 could serve as a therapeutic adjuvant for the treatment of PD. In the future, placebo-controlled studies are needed to further support the efficacy of PS128 supplementation.Clinical Trial Registration:https://clinicaltrials.gov/, identifier: NCT04389762.

scholarly journals Characterization of Nonmotor Symptoms in the MitoPark Mouse Model of Parkinson’s Disease

2020 ◽  
Author(s):  
Monica R. Langley ◽  
Shivani Ghaisas ◽  
Bharathi N. Palanisamy ◽  
Muhammet Ay ◽  
Huajun Jin ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Antidepressant Treatment ◽  
Forced Swim Test ◽  
Cognitive Learning ◽  
Motor Deficits ◽  
Motor Symptoms ◽  
Nonmotor Symptoms ◽  
Forced Swim ◽  
Non Motor Symptoms

AbstractMitochondrial dysfunction has been implicated as a key player in the pathogenesis of Parkinson’s disease (PD). The MitoPark mouse, a transgenic mitochondrial impairment model developed by specific inactivation of TFAM in dopaminergic neurons, spontaneously exhibits progressive motor deficits and neurodegeneration, recapitulating several features of PD. Since non-motor symptoms are now recognized as important features of the prodromal stage of PD, we monitored the clinically relevant motor and nonmotor symptoms from ages 8-24 wks in MitoPark mice and their littermate controls. As expected, motor deficits in MitoPark mice began around 12-14 wks and became severe by 16-24 wks. Interestingly, male MitoPark mice showed spatial memory deficits before female mice, beginning at 8 wks and becoming most severe at 16 wks, as determined by Morris water maze. When compared to age-matched control mice, MitoPark mice exhibited olfactory deficits in novel and social scent tests as early as 10-12 wks. MitoPark mice between 16-24 wks spent more time immobile in forced swim and tail suspension tests, and made fewer entries into open arms of the elevated plus maze, indicating a depressive and anxiety-like phenotype, respectively. Importantly, depressive behavior as determined by immobility in forced swim test was reversible by antidepressant treatment with desipramine. Collectively, our results indicate that MitoPark mice progressively exhibit deficits in cognitive learning and memory, olfactory discrimination, and anxiety-and depression-like behaviors. Thus, MitoPark mice can serve as an invaluable model for studying motor and non-motor symptoms in addition to studying pathology in PD.

Beta Oscillatory Activity in the Subthalamic Nucleus and Its Relation to Dopaminergic Response in Parkinson's Disease

2006 ◽  
Vol 96 (6) ◽  
pp. 3248-3256 ◽  
Author(s):  
Moran Weinberger ◽  
Neil Mahant ◽  
William D. Hutchison ◽  
Andres M. Lozano ◽  
Elena Moro ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Subthalamic Nucleus ◽  
Field Potential ◽  
Neuronal Population ◽  
Oscillatory Activity ◽  
Motor Deficits ◽  
Beta Activity ◽  
Beta Power ◽  
Dorsal Portion

Recent studies suggest that beta (15–30 Hz) oscillatory activity in the subthalamic nucleus (STN) is dramatically increased in Parkinson's disease (PD) and may interfere with movement execution. Dopaminergic medications decrease beta activity and deep brain stimulation (DBS) in the STN may alleviate PD symptoms by disrupting this oscillatory activity. Depth recordings from PD patients have demonstrated beta oscillatory neuronal and local field potential (LFP) activity in STN, although its prevalence and relationship to neuronal activity are unclear. In this study, we recorded both LFP and neuronal spike activity from the STN in 14 PD patients during functional neurosurgery. Of 200 single- and multiunit recordings 56 showed significant oscillatory activity at about 26 Hz and 89% of these were coherent with the simultaneously recorded LFP. The incidence of neuronal beta oscillatory activity was significantly higher in the dorsal STN ( P = 0.01) and corresponds to the significantly increased LFP beta power recorded in the same region. Of particular interest was a significant positive correlation between the incidence of oscillatory neurons and the patient's benefit from dopaminergic medications, but not with baseline motor deficits off medication. These findings suggest that the degree of neuronal beta oscillatory activity is related to the magnitude of the response of the basal ganglia to dopaminergic agents rather than directly to the motor symptoms of PD. The study also suggests that LFP beta oscillatory activity is generated largely within the dorsal portion of the STN and can produce synchronous oscillatory activity of the local neuronal population.

scholarly journals Neuropsychiatric and Cognitive Deficits in Parkinson’s Disease and Their Modeling in Rodents

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 684
Author(s):  
Mélina Decourt ◽  
Haritz Jiménez-Urbieta ◽  
Marianne Benoit-Marand ◽  
Pierre-Olivier Fernagut
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Learning And Memory ◽  
Cognitive Deficits ◽  
Cognitive Disorders ◽  
Alpha Synuclein ◽  
Motor Deficits ◽  
Motor Symptoms ◽  
Rodent Models ◽  
Non Motor Symptoms

Parkinson’s disease (PD) is associated with a large burden of non-motor symptoms including olfactory and autonomic dysfunction, as well as neuropsychiatric (depression, anxiety, apathy) and cognitive disorders (executive dysfunctions, memory and learning impairments). Some of these non-motor symptoms may precede the onset of motor symptoms by several years, and they significantly worsen during the course of the disease. The lack of systematic improvement of these non-motor features by dopamine replacement therapy underlines their multifactorial origin, with an involvement of monoaminergic and cholinergic systems, as well as alpha-synuclein pathology in frontal and limbic cortical circuits. Here we describe mood and neuropsychiatric disorders in PD and review their occurrence in rodent models of PD. Altogether, toxin-based rodent models of PD indicate a significant but non-exclusive contribution of mesencephalic dopaminergic loss in anxiety, apathy, and depressive-like behaviors, as well as in learning and memory deficits. Gene-based models display significant deficits in learning and memory, as well as executive functions, highlighting the contribution of alpha-synuclein pathology to these non-motor deficits. Collectively, neuropsychiatric and cognitive deficits are recapitulated to some extent in rodent models, providing partial but nevertheless useful options to understand the pathophysiology of non-motor symptoms and develop therapeutic options for these debilitating symptoms of PD.

Speech and Cognitive-Linguistic Function in Parkinson's Disease

2010 ◽  
Vol 20 (2) ◽  
pp. 31-38 ◽  
Author(s):  
Kristie Spencer ◽  
Janelle Sanchez ◽  
Audra McAllen ◽  
Phillip Weir
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Motor Deficits ◽  
Behavioral Management ◽  
Review Of The Literature ◽  
Cognitive Changes ◽  
Neurologic Disorders ◽  
Cardinal Symptoms ◽  
Non Motor Symptoms

Abstract Purpose: Parkinson's disease is among the most common of the motor-based progressive neurologic disorders. This article provides a review of the motor, cognitive, sensory-perceptual, and linguistic deficits that may occur as a result of the loss of dopaminergic neurons, which causes Parkinson's disease. Method: A review of the literature regarding the nature of Parkinson's disease points out the primary triad of symptoms, which are tremor, rigidity, and bradykinesia. Descriptions of these cardinal symptoms are discussed, as are the non-motor symptoms frequently seen in this disorder, including cognitive changes, sensory-perceptual deficits, and occasionally, linguistic deficits. Dysarthria and dysphagia are frequently seen as a result of the motor deficits associated with Parkinson's disease. Conclusions: Much has been learned about the pathogenesis of Parkinson's disease, which has led to improved pharmacologic, surgical, and behavioral management. Speech-language pathologists (SLPs) need to be aware of these advances in order to better assess and treat patients and educate families.

Association of the Non-Motor Burden with Patterns of Striatal Dopamine Loss in de novo Parkinson’s Disease

2020 ◽  
Vol 10 (4) ◽  
pp. 1541-1549
Author(s):  
Seok Jong Chung ◽  
Sangwon Lee ◽  
Han Soo Yoo ◽  
Yang Hyun Lee ◽  
Hye Sun Lee ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
Early Stage ◽  
Striatal Dopamine ◽  
Motor Deficits ◽  
Dopamine Depletion ◽  
Severe Motor ◽  
Severe Group ◽  
Striatal Dopamine Depletion

Background: Striatal dopamine deficits play a key role in the pathogenesis of Parkinson’s disease (PD), and several non-motor symptoms (NMSs) have a dopaminergic component. Objective: To investigate the association between early NMS burden and the patterns of striatal dopamine depletion in patients with de novo PD. Methods: We consecutively recruited 255 patients with drug-naïve early-stage PD who underwent 18F-FP-CIT PET scans. The NMS burden of each patient was assessed using the NMS Questionnaire (NMSQuest), and patients were divided into the mild NMS burden (PDNMS-mild) (NMSQuest score <6; n = 91) and severe NMS burden groups (PDNMS-severe) (NMSQuest score >9; n = 90). We compared the striatal dopamine transporter (DAT) activity between the groups. Results: Patients in the PDNMS-severe group had more severe parkinsonian motor signs than those in the PDNMS-mild group, despite comparable DAT activity in the posterior putamen. DAT activity was more severely depleted in the PDNMS-severe group in the caudate and anterior putamen compared to that in the PDMNS-mild group. The inter-sub-regional ratio of the associative/limbic striatum to the sensorimotor striatum was lower in the PDNMS-severe group, although this value itself lacked fair accuracy for distinguishing between the patients with different NMS burdens. Conclusion: This study demonstrated that PD patients with severe NMS burden exhibited severe motor deficits and relatively diffuse dopamine depletion throughout the striatum. These findings suggest that the level of NMS burden could be associated with distinct patterns of striatal dopamine depletion, which could possibly indicate the overall pathological burden in PD.

Intraoperative localization of spatially and spectrally distinct resting-state networks in Parkinson’s disease

2020 ◽  
Vol 132 (4) ◽  
pp. 1234-1242 ◽  
Author(s):  
Paolo Belardinelli ◽  
Ramin Azodi-Avval ◽  
Erick Ortiz ◽  
Georgios Naros ◽  
Florian Grimm ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Network Effects ◽  
Brain Activity ◽  
Dynamic Imaging ◽  
Oscillatory Activity ◽  
Network Information ◽  
Novel Approach ◽  
Electrophysiological Recordings ◽  
Intraoperative Localization

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for symptomatic Parkinson’s disease (PD); the clinical benefit may not only mirror modulation of local STN activity but also reflect consecutive network effects on cortical oscillatory activity. Moreover, STN-DBS selectively suppresses spatially and spectrally distinct patterns of synchronous oscillatory activity within cortical-subcortical loops. These STN-cortical circuits have been described in PD patients using magnetoencephalography after surgery. This network information, however, is currently not available during surgery to inform the implantation strategy.The authors recorded spontaneous brain activity in 3 awake patients with PD (mean age 67 ± 14 years; mean disease duration 13 ± 7 years) during implantation of DBS electrodes into the STN after overnight withdrawal of dopaminergic medication. Intraoperative propofol was discontinued at least 30 minutes prior to the electrophysiological recordings. The authors used a novel approach for performing simultaneous recordings of STN local field potentials (LFPs) and multichannel electroencephalography (EEG) at rest. Coherent oscillations between LFP and EEG sensors were computed, and subsequent dynamic imaging of coherent sources was performed.The authors identified coherent activity in the upper beta range (21–35 Hz) between the STN and the ipsilateral mesial (pre)motor area. Coherence in the theta range (4–6 Hz) was detected in the ipsilateral prefrontal area.These findings demonstrate the feasibility of detecting frequency-specific and spatially distinct synchronization between the STN and cortex during DBS surgery. Mapping the STN with this technique may disentangle different functional loops relevant for refined targeting during DBS implantation.

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