Increased bradykinesia in Parkinson’s disease with increased movement complexity: elbow flexion-extension movements

The present research investigates factors contributing to bradykinesia in the control of simple and complex voluntary limb movement in Parkinson’s disease (PD) patients. The functional scheme of the basal ganglia (BG)–thalamocortical circuit was described by a mathematical model based on the mean firing rates of BG nuclei. PD was simulated as a reduction in dopamine levels, and a loss of functional segregation between two competing motor modules. In order to compare model simulations with performed movements, flexion and extension at the elbow joint is taken as a test case. Results indicated that loss of segregation contributed to bradykinesia due to interference between competing modules and a reduced ability to suppress unwanted movements. Additionally, excessive neurotransmitter depletion is predicted as a possible mechanism for the increased difficulty in performing complex movements. The simulation results showed that the model is in qualitative agreement with the results from movement experiments on PD patients and healthy subjects. Furthermore, based on changes in the firing rate of BG nuclei, the model demonstrated that the effective mechanism of Deep Brain Stimulation (DBS) in STN may result from stimulation induced inhibition of STN, partial synaptic failure of efferent projections, or excitation of inhibitory afferent axons even though the underlying methods of action may be quite different for the different mechanisms

Levodopa-induced dyskinesia in Parkinson disease: Current and Evolving Concepts.

Levodopa‐induced dyskinesia is a common complication in Parkinson disease. Pathogenic mechanisms include phasic stimulation of dopamine receptors, nonphysiological levodopa‐to‐dopamine conversion in serotonergic neurons, hyperactivity of corticostriatal glutamatergic transmission, and overstimulation of nicotinic acetylcholine receptors on dopamine‐releasing axons. Delay in initiating levodopa is no longer recommended, as dyskinesia development is a function of disease duration rather than cumulative levodopa exposure. We review current and in‐development treatments for peak‐dose dyskinesia but suggest that improvements in levodopa delivery alone may reduce its future prevalence

Motor symptoms in Parkinson's disease: A unified framework

Parkinson’s disease (PD) is characterized by a range of motor symptoms. Besides the cardinal symptoms (akinesia and bradykinesia, tremor and rigidity), PD patients show additional motor deficits, including: gait disturbance, impaired handwriting, grip force and speech deficits, among others. Some of these motor symptoms (e.g., deficits of gait, speech, and handwriting) have similar clinical profiles, neural substrates, and respond similarly to dopaminergic medication and deep brain stimulation (DBS). Here, we provide an extensive review of the clinical characteristics and neural substrates of each of these motor symptoms, to highlight precisely how PD and its medical and surgical treatments impact motor symptoms. In conclusion, we offer a unified framework for understanding the range of motor symptoms in PD. We argue that various motor symptoms in PD reflect dysfunction of neural structures responsible for action selection, motor sequencing, and coordination and execution of movement

Effects of dance therapy on balance, gait and neuro-psychological performances in patients with Parkinson's disease and postural instability

Postural Instability (PI) is a core feature of Parkinson’s Disease (PD) and a major cause of falls and disabilities. Impairment of executive functions has been called as an aggravating factor on motor performances. Dance therapy has been shown effective for improving gait and has been suggested as an alternative rehabilitative method. To evaluate gait performance, spatial-temporal (S-T) gait parameters and cognitive performances in a cohort of patients with PD and PI modifications in balance after a cycle of dance therapy

Oculomotor Deficits in Diseases of the Basal Ganglia: Parkinson\u27s and Huntington\u27s Diseases

Oculomotor deficits are now recognized as being present in several neurological diseases of the basal ganglia. The present report will focus primarily on those observed in Huntington\u27s and Parkinson\u27s diseases. Neuronal cell loss in the pars compacta of the substantia nigra, degeneration of the nigrostriatal pathway, and consequent depletion of the neurotransmitter dopamine is the most obvious etiological abnormality in Parkinson\u27s disease. Huntington\u27s disease, on the other hand, involves the selective genetically-driven atrophy of the striatum (caudate and putamen). In order to attempt to understand oculomotor dysfunction, as a component of basal ganglia disease, it is necessary to first establish a definition of the basal ganglia, its relevant connections, and their associated neurotransmitters and functions

Circuit-level analyses of cortico-basal ganglia-thalamic networks. Effects of dopamine dysregulation and experience dependent plasticity.

The cortico-basal ganglia-thalamic (CBT) circuit is thought to be involved in control of voluntary and goal-directed movements and action selection. Dopamine is known to play a crucial role in this circuit and regulating its activity. The important role of dopamine is particularly evident in Parkinson’s patients, where dopaminergic cells are dying and motor impairments follow. While dopamine replacement is an effective therapy, satisfactory alleviation only lasts for a limited number of years, after which patients frequently develop side-effects in the form of levodopa-induced dyskinesia. In order to clarify the neurophysiological consequences of dopamine dysregulation we have here investigated the electrophysiological activity of each part of the CBT-loop in rats during different experimental conditions, using custom made multi-channel electrodes. Neuronal activity changes in 16 CBT structures were characterized upon acute pharmacological dopaminergic manipulations and firing rate changes of subgroup of cells within different structures in the CBT circuit were shown to potentially be responsible for the severe akinesia induced by the drugs. We have also developed a novel method to monitor the global state of the CBT circuit in a rat model of levodopa-induced dyskinesia and showed how this approach can be used to help developing new pharmacological therapies. Lastly, to investigate how somatosensory input is affecting motor circuits, we have recorded activity of the whole CBT-loop in rats before and after extensive skilled forelimb reaching and grasping training. Preliminary results show that only the motor cortex display experience-dependent changes due to the reaching training