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Neuron Mar 2019Parkinson's disease (PD) is a complex, multi-system neurodegenerative disorder. The second most common neurodegenerative disorder after Alzheimer's disease, it affects... (Review)
Review
Parkinson's disease (PD) is a complex, multi-system neurodegenerative disorder. The second most common neurodegenerative disorder after Alzheimer's disease, it affects approximately 1% of adults over age 60. Diagnosis follows the development of one or more of the core motor features of the disease, including tremor, slowing of movement (bradykinesia), and rigidity. However, there are numerous other motor and nonmotor disease manifestations. Many PD symptoms result directly from neurodegeneration; others are driven by aberrant activity patterns in surviving neurons. This latter phenomenon, PD circuit dysfunction, is an area of intense study, as it likely underlies our ability to treat many disease symptoms in the face of (currently) irreversible neurodegeneration. This Review will discuss key clinical features of PD and their basis in neural circuit dysfunction. We will first review important disease symptoms and some of the responsible neuropathology. We will then describe the basal ganglia-thalamocortical circuit, the major locus of PD-related circuit dysfunction, and some of the models that have influenced its study. We will review PD-related changes in network activity, subdividing findings into those that touch on the rate, rhythm, or synchronization of neurons. Finally, we suggest some critical remaining questions for the field and areas for new developments.
Topics: Basal Ganglia; Brain; Cerebral Cortex; Humans; Neural Pathways; Parkinson Disease; Thalamus
PubMed: 30897356
DOI: 10.1016/j.neuron.2019.03.004 -
Brain : a Journal of Neurology Mar 2020Bradykinesia is one of the cardinal motor symptoms of Parkinson's disease and other parkinsonisms. The various clinical aspects related to bradykinesia and the... (Review)
Review
Bradykinesia is one of the cardinal motor symptoms of Parkinson's disease and other parkinsonisms. The various clinical aspects related to bradykinesia and the pathophysiological mechanisms underlying bradykinesia are, however, still unclear. In this article, we review clinical and experimental studies on bradykinesia performed in patients with Parkinson's disease and atypical parkinsonism. We also review studies on animal experiments dealing with pathophysiological aspects of the parkinsonian state. In Parkinson's disease, bradykinesia is characterized by slowness, the reduced amplitude of movement, and sequence effect. These features are also present in atypical parkinsonisms, but the sequence effect is not common. Levodopa therapy improves bradykinesia, but treatment variably affects the bradykinesia features and does not significantly modify the sequence effect. Findings from animal and patients demonstrate the role of the basal ganglia and other interconnected structures, such as the primary motor cortex and cerebellum, as well as the contribution of abnormal sensorimotor processing. Bradykinesia should be interpreted as arising from network dysfunction. A better understanding of bradykinesia pathophysiology will serve as the new starting point for clinical and experimental purposes.
Topics: Animals; Humans; Hypokinesia; Levodopa; Neural Pathways; Parkinsonian Disorders
PubMed: 31834375
DOI: 10.1093/brain/awz344 -
Internal Medicine (Tokyo, Japan) Jan 2020Various methods of rehabilitation for dysphagia have been suggested through the experience of treating stroke patients. Although most of these patients recover their... (Review)
Review
Various methods of rehabilitation for dysphagia have been suggested through the experience of treating stroke patients. Although most of these patients recover their swallowing function in a short period, dysphagia in Parkinson's disease (PD) and Parkinson-related disorder (PRD) degenerates with disease progression. Muscle rigidity and bradykinesia are recognized as causes of swallowing dysfunction, and it is difficult to easily apply the strategies for stroke to the rehabilitation of dysphagia in PD patients. Disease severity, weight loss, drooling, and dementia are important clinical predictors. Silent aspiration is a pathognomonic sign that may lead to aspiration pneumonia. Severe PD patients need routine video fluoroscopy or video endoscopy to adjust their food and liquid consistency. Patients with PRD experience rapid progression of swallowing dysfunction. Nutrition combined with nasogastric tube feeding or percutaneous endoscopic gastrostomy feeding should be considered owing to the increased risk of aspiration and difficulty administrating oral nutrition.
Topics: Deglutition; Deglutition Disorders; Disease Progression; Enteral Nutrition; Humans; Hypokinesia; Muscle Rigidity; Parkinson Disease; Pneumonia, Aspiration; Respiratory Aspiration; Stroke Rehabilitation
PubMed: 30996170
DOI: 10.2169/internalmedicine.2373-18 -
Clinical Interventions in Aging 2020Bradykinesia and muscle weaknesses are common symptoms of Parkinson's Disease (PD) and are associated with impaired functional performance, increased risk of falls, and... (Clinical Trial)
Clinical Trial
PURPOSE
Bradykinesia and muscle weaknesses are common symptoms of Parkinson's Disease (PD) and are associated with impaired functional performance, increased risk of falls, and reduced quality of life. Recent studies have pointed to progressive resistance training (PRT) as an effective method to control and reduce these symptoms, increasing possibilities to treat the disease. However, few studies have focused on assessing the PRT effects in the short-term. Therefore, the present study aimed to assess the short-term PRT effects on people with PD, in order to offer new parameters for a better understanding of its effects, so as an adequation and PRT use as a complementary therapy.
PATIENTS AND METHODS
Forty individuals diagnosed with PD from stage 1 to 3 on the Hoehn and Yahr scale took part on the study and were allocated into 2 groups; Training Group (TG) performed a 9-week RT program twice a week, and the Control Group (CG) attended disease lectures. Bradykinesia UPDRS subscale (BSS), knee extensors isokinetic strength, Ten Meters Walk Test (TMW), Timed Up&Go Test (TUG) and 30-Second Chair Stand (T30) were measured before and after the intervention period. Statistical significance was set at p ≤ 0.05.
RESULTS
Significant time was noted by the group interaction for all functional tests (TUG, T30, and TWM; all p < 0.01) and BSS (p < 0.01). Post hoc analyses revealed that these differences were driven by significant improvements in these dependent variables (all p < 0.01) while the CG remained unchanged (all p > 0.05). Moreover, TUG, T30, TWM, and BSS were significantly different between TG and CG in the post-training assessments (all p < 0.01). Isokinetic muscle strength was slightly increased in the TG (2.4%) and decreased in the CG (-2.2%), but statistical analyses did not reach significance for interaction but only a trend (p = 0.12).
CONCLUSION
The results indicate that 9 weeks of PRT reduces bradykinesia and improves functional performance in patients with mild to moderate PD. These findings reinforce this mode of exercise as an important component of public health promotion programs for PD.
Topics: Age Factors; Aged; Aged, 80 and over; Disability Evaluation; Female; Humans; Hypokinesia; Knee; Male; Middle Aged; Muscle Strength; Parkinson Disease; Physical Functional Performance; Physical Therapy Modalities; Quality of Life; Resistance Training; Severity of Illness Index; Sex Factors
PubMed: 32158202
DOI: 10.2147/CIA.S231359 -
Parkinsonism & Related Disorders Jan 2016Although Deep Brain Stimulation (DBS) is an established treatment for Parkinson's disease (PD), there are still limitations in terms of effectivity, side-effects and... (Review)
Review
Although Deep Brain Stimulation (DBS) is an established treatment for Parkinson's disease (PD), there are still limitations in terms of effectivity, side-effects and battery consumption. One of the reasons for this may be that not only pathological but also physiological neural activity can be suppressed whilst stimulating. For this reason, adaptive DBS (aDBS), where stimulation is applied according to the level of pathological activity, might be advantageous. Initial studies of aDBS demonstrate effectiveness in PD, but there are still many questions to be answered before aDBS can be applied clinically. Here we discuss the feedback signals and stimulation algorithms involved in adaptive stimulation in PD and sketch a potential road-map towards clinical application.
Topics: Animals; Brain-Computer Interfaces; Deep Brain Stimulation; Humans; Hypokinesia; Parkinson Disease; Subthalamic Nucleus; Tremor
PubMed: 26411502
DOI: 10.1016/j.parkreldis.2015.09.028 -
Nature Jul 2010Neural circuits of the basal ganglia are critical for motor planning and action selection. Two parallel basal ganglia pathways have been described, and have been...
Neural circuits of the basal ganglia are critical for motor planning and action selection. Two parallel basal ganglia pathways have been described, and have been proposed to exert opposing influences on motor function. According to this classical model, activation of the 'direct' pathway facilitates movement and activation of the 'indirect' pathway inhibits movement. However, more recent anatomical and functional evidence has called into question the validity of this hypothesis. Because this model has never been empirically tested, the specific function of these circuits in behaving animals remains unknown. Here we report direct activation of basal ganglia circuitry in vivo, using optogenetic control of direct- and indirect-pathway medium spiny projection neurons (MSNs), achieved through Cre-dependent viral expression of channelrhodopsin-2 in the striatum of bacterial artificial chromosome transgenic mice expressing Cre recombinase under control of regulatory elements for the dopamine D1 or D2 receptor. Bilateral excitation of indirect-pathway MSNs elicited a parkinsonian state, distinguished by increased freezing, bradykinesia and decreased locomotor initiations. In contrast, activation of direct-pathway MSNs reduced freezing and increased locomotion. In a mouse model of Parkinson's disease, direct-pathway activation completely rescued deficits in freezing, bradykinesia and locomotor initiation. Taken together, our findings establish a critical role for basal ganglia circuitry in the bidirectional regulation of motor behaviour and indicate that modulation of direct-pathway circuitry may represent an effective therapeutic strategy for ameliorating parkinsonian motor deficits.
Topics: Animals; Basal Ganglia; Channelrhodopsins; Chromosomes, Artificial, Bacterial; Disease Models, Animal; Gait; Hypokinesia; Integrases; Mice; Mice, Transgenic; Models, Neurological; Motor Activity; Neostriatum; Neural Pathways; Neurons; Oxidopamine; Parkinson Disease; Psychomotor Performance; Receptors, Dopamine
PubMed: 20613723
DOI: 10.1038/nature09159 -
Movement Disorders : Official Journal... Apr 2023
Topics: Humans; Hypokinesia; Parkinson Disease
PubMed: 36847357
DOI: 10.1002/mds.29362