Cerebellar role in Parkinson's disease

Mirdamadi, Jasmine L.

doi:10.1152/jn.01132.2015

Cited by 69 publications

(35 citation statements)

References 14 publications

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“…In particular, cerebellum is involved in compensatory responses of brain to impaired movement control [15], which also occurs in rats exposed to acute hypobaric hypoxia. The movement disorders in Parkinson disease affecting cerebellum [16,17] have been associated with perturbations in cerebellar pool of amino acids and their signaling [18]. These biochemical changes in cerebellum may be further translated into behavioral changes because of high interconnectivity in the brain [16,19].…”

Section: Introductionmentioning

confidence: 99%

Hypoxic Adaptation of Mitochondrial Metabolism in Rat Cerebellum Decreases in Pregnancy

Граф

Trofimova

Ksenofontov

et al. 2020

Cells

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Function of brain amino acids as neurotransmitters or their precursors implies changes in the amino acid levels and/or metabolism in response to physiological and environmental challenges. Modelling such challenges by pregnancy and/or hypoxia, we characterize the amino acid pool in the rat cerebellum, quantifying the levels and correlations of 15 amino acids and activity of 2-oxoglutarate dehydrogenase complex (OGDHC). The parameters are systemic indicators of metabolism because OGDHC limits the flux through mitochondrial TCA cycle, where amino acids are degraded and their precursors synthesized. Compared to non-pregnant state, pregnancy increases the cerebellar content of glutamate and tryptophan, decreasing interdependence between the quantified components of amino acid metabolism. In response to hypoxia, the dependence of cerebellar amino acid pool on OGDHC and the average levels of arginine, glutamate, lysine, methionine, serine, phenylalanine, and tryptophan increase in non-pregnant rats only. This is accompanied by a higher hypoxic resistance of the non-pregnant vs. pregnant rats, pointing to adaptive significance of the hypoxia-induced changes in the cerebellar amino acid metabolism. These adaptive mechanisms are not effective in the pregnancy-changed metabolic network. Thus, the cerebellar amino acid levels and OGDHC activity provide sensitive markers of the physiology-dependent organization of metabolic network and its stress adaptations.

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Section: Introductionmentioning

confidence: 99%

Hypoxic Adaptation of Mitochondrial Metabolism in Rat Cerebellum Decreases in Pregnancy

Граф

Trofimova

Ksenofontov

et al. 2020

Cells

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“…It is therefore not clear whether certain parts of the cerebellum are more implicated than others in relation to motor and non-motor functioning in PD. Finally, the potential role of the cerebellum in PD has been discussed elsewhere in narrative reviews (40,41), but the cerebellar involvement remains largely unclear, especially in regards to the pathological and/or compensatory mechanisms at play. With exception of one meta-analysis of cerebellar gray matter atrophy across several neurodegenerative conditions (that did not report any findings in PD patients) (26), the existing literature lacks a quantitative and systematic review of cerebellar findings in PD based upon functional neuroimaging methods.…”

Section: Introductionmentioning

confidence: 99%

Cerebellar Contribution to Motor and Non-motor Functions in Parkinson's Disease: A Meta-Analysis of fMRI Findings

2020

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Background: Parkinson's disease (PD) results in both motor and non-motor symptoms. Traditionally, the underlying mechanism of PD has been linked to neurodegeneration of the basal ganglia. Yet it does not adequately account for the non-motor symptoms of the disease, suggesting that other brain regions may be involved. One such region is the cerebellum, which is known to be involved, together with the basal ganglia, in both motor and non-motor functions. Many studies have found the cerebellum to be hyperactive in PD patients, a finding that is seldom discussed in detail, and warrants further examination. The current study thus aims to examine quantitively the current literature on the cerebellar involvement in both motor and non-motor functioning in PD. Methods: A meta-analysis of functional neuroimaging literature was conducted with Seed-based D mapping. Only the studies testing functional activation in response to motor and non-motor paradigms in PD and healthy controls (HC) were included in the meta-analysis. Separate analyses were conducted by including only studies with non-motor paradigms, as well as meta-regressions with UPDRS III scores and disease duration. Results: A total of 57 studies with both motor and non-motor paradigms fulfilled our inclusion criteria and were included in the meta-analysis, which revealed hyperactivity in Crus I-II and vermal III in PD patients compared to HC. An analysis including only studies with cognitive paradigms revealed a cluster of increased activity in PD patients encompassing lobule VIIB and VIII. Another meta-analysis including the only 20 studies that employed motor paradigms did not reveal any significant group differences. However, a descriptive analysis of these studies revealed that 60% of them reported cerebellar hyperactivations in PD and included motor paradigm with significant cognitive task demands, as opposed to 40% presenting the opposite pattern and using mainly force grip tasks. The meta-regression with UPDRS III scores found a negative association between motor scores and activation in lobule VI and vermal VII-VIII. No correlation was found with disease duration. Solstrand Dahlberg et al. Cerebellar Activity in PD Discussion: The present findings suggest that one of the main cerebellar implications in PD is linked to cognitive functioning. The negative association between UPDRS scores and activation in regions implicated in motor functioning indicate that there is less involvement of these areas as the disease severity increases. In contrast, the lack of correlation with disease duration seems to indicate that the cerebellar activity may be a compensatory mechanism to the dysfunctional basal ganglia, where certain sub-regions of the cerebellum are employed to cope with motor demands. Yet future longitudinal studies are needed to fully address this possibility.

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“…A possible factor for the larger motor adaptation ability in PD patients is compensatory cerebellar function 28 . The cerebellum plays essential roles in motor adaptation 1,4 .…”

Section: Discussionmentioning

confidence: 99%

“…Cerebellar ataxia patients have shown deficits in updating the internal model in motor adaptation experiments 1,4,5 . Although it is widely known that PD patients have paretic symptoms related to dopamine or the basal ganglia, a recent finding supported the possibility that they have compensatory cerebellar functions 28 . The compensatory function in PD patients can be supported by not only anatomical connectivities between the cerebellum and basal ganglia 29 but also resting and functional connectivities 30 .…”

Section: Discussionmentioning

confidence: 99%

Larger, but not better, motor adaptation ability inherent in medicated Parkinson’s disease patients revealed by a smart-device-based study

Takiyama

Sakurada

Shinya

et al. 2020

Sci Rep

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Generating appropriate motor commands is an essential brain function. to achieve proper motor control in diverse situations, predicting future states of the environment and body and modifying the prediction are indispensable. the internal model is a promising hypothesis about brain function for generating and modifying the prediction. Although several findings support the involvement of the cerebellum in the internal model, recent results support the influence of other related brain regions on the internal model. A representative example is the motor adaptation ability in parkinson's disease (pD) patients. Although this ability provides some hints about how dopamine deficits and other PD symptoms affect the internal model, previous findings are inconsistent; some reported a deficit in the motor adaptation ability in pD patients, but others reported that the motor adaptation ability of pD patients is comparable to that of healthy controls. A possible factor causing this inconsistency is the difference in task settings, resulting in different cognitive strategies in each study. Here, we demonstrate a larger, but not better, motor adaptation ability in pD patients than in healthy controls while reducing the involvement of cognitive strategies and concentrating on implicit motor adaptation abilities. this study utilizes a smart-device-based experiment that enables motor adaptation experiments anytime and anywhere with less cognitive strategy involvement. The PD patients showed a significant response to insensible environmental changes, but the response was not necessarily suitable for adapting to the changes. Our findings support compensatory cerebellar functions in PD patients from the perspective of motor adaptation.Motor adaptation is an essential brain function that modifies motor commands to achieve desired movements in novel situations, such as adapting to use new tools or correcting a movement error. A promising hypothesis about motor adaptation is the internal model hypothesis, which considers the cerebellum to play a role not only in predicting future states of the environment and the body but also in modifying the prediction 1 . Appropriate motor commands can be generated through the outcome predicted by the internal model. To investigate the ability to update the internal model, a motor adaptation paradigm is used 2,3 . In this paradigm, the environment changes through artificially applied perturbations. The subjects thus need to update their internal models to achieve the desired movements while compensating for the perturbation.PD was diagnosed clinically according to the UK PD Society Brain Bank criteria. All of the patients had bradykinesia and at least one of the three features of PD: 4-6 Hz resting tremor, rigidity, and postural instability. All of the PD patients had asymmetric onset and showed a positive response to dopaminergic medication. None exhibited atypical symptoms such as severe gaze palsy or symptomatic dysautonomia. All PD patients participated in the experiment approximately 1-3 hours a...

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Cerebellar role in Parkinson's disease

Cited by 69 publications

References 14 publications

Hypoxic Adaptation of Mitochondrial Metabolism in Rat Cerebellum Decreases in Pregnancy

Hypoxic Adaptation of Mitochondrial Metabolism in Rat Cerebellum Decreases in Pregnancy

Cerebellar Contribution to Motor and Non-motor Functions in Parkinson's Disease: A Meta-Analysis of fMRI Findings

Larger, but not better, motor adaptation ability inherent in medicated Parkinson’s disease patients revealed by a smart-device-based study

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